Divalproex sodium: Nupharm V/S FDA

Fdalawblog has published a very interesting article on Divalproex sodium delayed-release 500 mg tablets

Earlier this month, we reported on a complaint filed by Nu-Pharm Inc. against FDA in the U.S. District Court for the District of Columbia seeking declaratory and injunctive relief with respect to the company’s Abbreviated New Drug Application ("ANDA") #77-615 for generic divalproex sodium delayed-release 500 mg tablets. Divalproex sodium delayed-release 500 mg tablets is marketed by Abbott Laboratories under the trade name DEPAKOTE. Nu-Pharm’s ANDA contained a paragraph IV certification to the Orange Book-listed patents for DEPAKOTE, Abbott sued within the statutory 45-day period, and the 30-month stay triggered by the suit reportedly expired in November 2007. Late last week, the court dismissed the complaint in a one-page order.According to Nu-Pharm’s memorandum in support of a temporary restraining order and/or preliminary injunction, FDA must approve ANDA #77-615 because the company satisfied all requirements for final ANDA approval and the 30-month stay of approval triggered by the submission of Nu-Pharm’s ANDA with a paragraph IV patent certification expired without a substantive ruling on patent validity or infringement. FDA nevertheless refused to approve ANDA #77-615 based on an order entered in a contempt proceeding by the U.S. District Court for the Northern District of Illinois (Eastern Division) (Judge Richard Posner sitting by designation) involving an ANDA with a paragraph IV patent certification for generic DEPAKOTE submitted by Apotex Inc. (which formerly owned Nu-Pharm) that also extended to Nu-Pharm’s product.In October 2007, the U.S. Court of Appeals for the Federal Circuit reversed the district court’s contempt judgment in the Apotex case with respect to Apotex acting in concert with Nu-Pharm to submit an ANDA "because the district court erred in finding Apotex in contempt when the conduct at issue was not within the express terms of the injunction." The Federal Circuit also held, however, that the contempt procedure used by the Illinois court was proper, that Nu-Pharm’s divalproex sodium drug product was not colorably different from Apotex’s divalproex sodium drug product, and that Nu-Pharm’s product would infringe patents covering DEPAKOTE. Apotex’s request for the Federal Circuit to hear the case en banc was denied, and in January 2008, the company petitioned the Supreme Court for review.Nu-Pharm contends that notwithstanding the order in the Illinois court contempt proceeding –to which Nu-Pharm was not and is not a party- FDA is required to approve ANDA #77-615 under the plain language of FDC Act § 505(j)(5)(B)(iii), which states, in relevant part:If the applicant made a [paragraph IV certification], the approval shall be made effective immediately unless, before the expiration of 45 days after the date on which the notice described in [FDC Act § 505(j)(2)(B)] is received, an action is brought for infringement of the patent that is the subject of the certification and for which information was submitted to the Secretary under FDC Act § 505(b)(1) or § 505(c)(2)] before the date on which the application (excluding an amendment or supplement to the application), which the Secretary later determines to be substantially complete, was submitted. If such an action is brought before the expiration of such days, the approval shall be made effective upon the expiration of the thirty-month period beginning on the date of the receipt of the notice provided under [FDC Act § 505(j)(2)(B)(i)] or such shorter or longer period as the court may order because either party to the action failed to reasonably cooperate in expediting the action, except that . . .(II) if before the expiration of such period the district court decides that the patent has been infringed . . . .Specifically, Nu-Pharm argues, among other things, that "for purposes of ANDA approval, the only action that matters is the one brought against the particular ANDA applicant within the 45-day period for infringement of the patent that is the subject of the applicant’s paragraph IV certification."FDA, in the Agency’s memorandum accompanying its motion to dismiss, comments in response to Nu-Pharm’s statutory plain meaning arguments that:FDA must give effect to the [Illinois] court’s order, which expressly pertains to Nu-Pharm. . . . While Nu-Pharm is correct that FDA must ordinarily approve an otherwise approvable ANDA upon expiration of a 30-month stay, in this case, FDA is subject to a direct court order requiring FDA to delay the approval of Nu-Pharm’s ANDA until after January 29, 2008. Thus, Nu-Pharm’s statutory arguments miss the point entirely because Nu-Pharm fails to recognize (at least before this Court) FDA’s obligation to give effect to the Illinois court’s order. For this reason, Nu-Pharm’s lengthy statutory arguments are irrelevant.FDA goes on to cite two cases in which courts have rejected arguments that FDA’s decision to follow court orders were improper because they were inconsistent with the FDC Act.Although Nu-Pharm was unsuccessful in convincing the U.S. District Court for the District of Columbia to grant declaratory and injunctive relief, the company has expressed its intent to appeal the decision. Specifically, in Nu-Pharm’s brief, the company states:[I]n the event the Court denies Nu-Pharm’s request for emergency injunctive relief, Nu-Pharm respectfully requests that any adverse FDA decision be stayed and that Nu-Pharm’s 500 mg product be finally approved pending review by, and appeal of this matter to, the United States Court of Appeals for the D.C. Circuit

Pentoprazole News

The fight on genric pentoprazole has started and generic players Teva, Sun Pharma, Caraco and innovator Wyeth has released following press releases
Sun Pharma launched Pentoprazole in USA
Sun Pharmaceutical Industries Ltd. announced today that it has commercially launched generic Pantoprazole Sodium Delayed Release (DR) Tablets, 40 mg, which is AB-rated to Wyeth's Protonix® DR Tablets. Sun's product is being sold in the United States by its marketing partner Caraco Pharmaceutical Laboratories. Sun Pharma had received a USFDA approval for these tablets in Sep 2007. This strength of Pantoprazole Sodium has annual sales of approximately USD 2.3 billion in the US.Sun's launch was initiated after the December 22, 2007 commercial launch by Teva Pharmaceutical Industries Ltd. of generic Pantoprazole Sodium tablet products, and after the January 29, 2008 commercial launch by Wyeth of generic Pantoprazole Sodium tablets product through its designated distributor.Sun shares a 180-day period of marketing exclusivity with Teva for this product. Sun is currently involved in patent litigation with Wyeth and Altana (now Nycomed) concerning this product in the U.S. District Court for the District of New Jersey. Although no trial date has yet been set, in September 2007, the District Court denied a motion filed by Wyeth and Altana for a preliminary injunction related to Sun's Pantoprazole Tablets. Wyeth and Altana have appealed the District Court's decision.

Caraco to market Sun Pharma Pentoprazole
Caraco Pharma announced today that it has launched Pantoprazole Sodium Delayed-Release Tablets, 40 mg (Pantoprazole Sodium DR), which is AB-rated to Wyeth's Protonix(R) DR Tablets, on behalf of Sun Pharmaceutical Industries, Ltd. (Sun Pharma). Sun Pharma recently received approval from the US Food and Drug Administration (FDA) for its Abbreviated New Drug Application (ANDA) for generic Protonix(R), and being one of the first-to-file an ANDA with a Paragraph IV certification, shares a 180-day marketing exclusivity with Teva Pharmaceutical Industries Ltd.Caraco's launch on behalf of Sun Pharma was initiated after the December 22, 2007 launch by Teva Pharmaceutical Industries Ltd. of generic Pantoprazole Sodium DR tablet products, and after the January 29, 2008 launch by Wyeth of generic Pantoprazole Sodium DR tablets product through its designated distributor.Sun Pharma is currently involved in patent litigation with Wyeth and Altana (recently acquired by Nycomed) concerning this product in the U.S. District Court for the District of New Jersey. Although no trial date has yet been set, in September 2007, the District Court denied a motion filed by Wyeth and Altana for a preliminary injunction related to Sun's Pantoprazole Tablets. Wyeth and Altana have appealed the District Court's decision.Pantoprazole Sodium DR is indicated for the short-term treatment (up to eight weeks) in the healing and symptomatic relief of erosive esophagitis, is indicated for the maintenance of healing erosive esophagitis and reduction in relapse rates of daytime and nighttime heartburn symptoms in patients with gastroesophageal reflux disease (GERD), and is indicated for the long-term treatment of pathological hypersecretory conditions, including Zollinger- Ellison syndrome. This new product is bioequivalent to Protonix(R), a registered trademark of Wyeth Pharmaceuticals Inc. Protonix(R) 40 mg tablets had U.S. sales of approximately $2.3 billion for the 12-month period ended September 30, 2007, according to IMS Data.Detroit-based Caraco Pharmaceutical Laboratories, Ltd., develops, manufactures, markets and distributes generic and private-label pharmaceuticals to the nation's largest wholesalers, distributors, drugstore chains and managed care providers.

Prasco to distribute authorized generic Pentoprazole

Wyeth and its business partner, Nycomed, today announced the U.S. launch of Wyeth's own generic version of PROTONIX(R) tablets, in response to the at-risk launch of generic pantoprazole tablets in the U.S. by Teva Pharma, on December 21, 2007. Wyeth's own generic version of PROTONIX will be distributed by Prasco starting today."Compound patents, like that infringed by Teva, represent the foundation of pharmaceutical innovation, a critical underpinning in bringing important new medicines to patients," says Bernard Poussot, President and Chief Executive Officer for Wyeth. "We believe the PROTONIX compound patent is strong and we will vigorously pursue our litigation against Teva and other infringing generics. Going forward, we will continue to seek an injunction against any infringement of this patent, as well as monetary damages, including lost profits, from Teva."Wyeth and Altana Pharma AG (recently acquired by Nycomed) sued Teva and Sun Pharmaceuticals for patent infringement based on Teva's and Sun's filing of Abbreviated New Drug Applications (ANDAs) seeking U.S. Food and Drug Administration (FDA) approval to market generic versions of PROTONIX before the patent expires on July 19, 2010. Under the Hatch-Waxman Act, the filing of the lawsuit stayed final FDA approval of Teva's ANDA until August 2, 2007, and Sun's ANDA until September 8, 2007. On September 6, 2007, The United States District Court for the District of New Jersey denied Wyeth's and Nycomed's motion for preliminary injunction. The Court did not rule on the validity of the patent, but rather concluded that, based on the limited record before it, Wyeth and Nycomed were not entitled to the extraordinary relief of a preliminary injunction. Trial is expected in the second half of 2008.
Prasco announced today that, pursuant to an agreement it entered into with the ESI Lederle Division of Wyeth ("ESI"), it is shipping the generic version of PROTONIX(R) (Pantoprazole Sodium) Delayed-Release Tablets being offered for sale by ESI. Prasco, as ESI's agent and on ESI's behalf, will solicit orders for and distribute the 20 mg and 40 mg formulations of Pantoprazole Sodium Delayed-Release (DR) Tablets to all trade classes in the U.S. under the ESI Lederle label. Pantoprazole Sodium DR Tablets are AB-rated, therapeutically equivalent and substitutable for the brand PROTONIX Delayed-Release (DR) Tablets."We are extremely pleased to have established this agreement with Wyeth, a global leader in the pharmaceutical industry," said Prasco Chief Executive Officer E. Thomas Arington. "Pantoprazole Sodium DR Tablets are identical to PROTONIX DR Tablets, providing the consuming marketplace the benefits of competitive balance and brand-quality at generic prices," stated Arington.PROTONIX DR Tablets had reported sales of $2.5 billion dollars in the United States, with over 19 million prescriptions filled for the twelve months ended November 30, 2007, based on IMS sales data. PROTONIX is a registered trademark of Wyeth Pharmaceuticals, Inc.

Teva announced termination of agreement with Wyeth
Teva Pharma announced today that the Company's standstill agreement with Wyeth/Altana regarding additional shipments by Teva of generic Protonix (Pantoprazole Sodium) has terminated as a result of Wyeth's launch of an authorized generic product.Teva is currently involved in patent litigation with Wyeth/Altana concerning this product in the U.S. District Court for the District of New Jersey. A trial date has not been set.In September 2007, the District Court denied a motion filed by Wyeth/Altana for a preliminary injunction related to Teva's Pantoprazole Tablets. In that decision, the Court found that Wyeth/Altana did not meet its burden of proving likelihood of success on the merits. Wyeth/Altana have appealed that decision.

Mylan updates on Lorazepam and Clorazepate antitrust cases

Mylan today announced that it intends to appeal a Jan. 24, 2008 decision by the U.S. District Court for the District of Columbia against Mylan and its co- defendants Cambrex Corporation and Gyma Laboratories in the last of the pending Lorazepam and Clorazepate antitrust cases. The first related suit had been filed in 1998. As previously disclosed, in June 2005, a jury in the district court had rendered a verdict against Mylan and its co-defendants. The parties subsequently filed various post-trial motions, and the January 24 decision resolved several of those motions. The district court ordered Mylan to pay $35,906,922. The court also ordered Cambrex and Gyma to pay $16,709,242 each, some or all of which may be subject to indemnification obligations by Mylan. Plaintiffs' motion for attorneys' fees remains pending. Mylan intends to immediately appeal the decision and will continue to vigorously defend itself in the litigation. Mylan Inc. is one of the world's leading quality generic and specialty pharmaceutical companies. The Company offers one of the industry's broadest and highest quality product portfolios, a robust product pipeline and a global commercial footprint through operations in more than 90 countries. Through its controlling interest in Matrix Laboratories Limited, Mylan has direct access to one of the largest active pharmaceutical ingredient (API) manufacturers in the world. Dey, L.P., Mylan's fully integrated specialty business, provides the Company with innovative and diversified opportunities in the respiratory and allergy therapeutic areas.

Endo Pharma filed a lawsuit against Impax on Oxymorphone HCl extended-release tablets

Endo Pharma and Penwest Pharma announced today that they have filed a lawsuit against Impax Lab in the United States District Court for the District of Delaware in connection with Impax's Abbreviated New Drug Application (ANDA) for Opana ER (Oxymorphone HCl) extended-release tablets . The lawsuit is in response to IMPAX's notice to Endo and Penwest, announced on December 17, 2007, advising of the FDA's acceptance for substantive review, as of November 23, 2007, of IMPAX's ANDA containing a Paragraph IV certification under 21 U.S.C. Section 355(j) forOxymorphone hydrochloride extended-release tablets CII. IMPAX stated in its Paragraph IV certification notice letter that the FDA requested IMPAX to provide notification to Endo and Penwest of this certification.IMPAX's Paragraph IV certification notice refers to certain Penwest patents listed in the FDA's Orange Book relating to the formulation of OPANA ER. The complaint filed today alleges infringement of certain of these Orange Book-listed patents.As previously disclosed, Endo and Penwest filed a lawsuit against IMPAX on November 15, 2007 in the United States District Court for the District of Delaware in response to a series of Paragraph IV certification notices that Endo and Penwest assert were wrongfully served on them by IMPAX. These prior Paragraph IV Certification Notices related to the same Orange Book-listed patents for OPANA ER and were served on Endo and Penwest after the acceptance of IMPAX's ANDA was rescinded by the FDA. Endo and Penwest continue to believe that these prior Paragraph IV Certification Notices are null, void and of no legal effect.OPANA ER has been granted new dosage form regulatory exclusivity that prevents the FDA from approving any ANDA for a generic version of OPANA ER for launch prior to June 22, 2009, the date such regulatory exclusivity expires.

Gilead’s loss, Cipla’s gain

The US Patent and Trademark Office’s (USPTO) rejection of Gilead Sciences’ patent application for the AIDS drug, Viread, is expected to have a strong impact in the Indian as well as global HIV/AIDS drug market. The rejection may affect the decision of the Indian Patent Office on Gilead’s patent application for Viread here. Last year, Cipla had filed a pre-grant opposition with the Indian patent office against Viread, the much sought after second line AIDS drug, arguing that the grant of the patent in India will make the HIV drug unaffordable to patients worldwide.
On Wednesday, USPTO rejected four patents on Viread, claiming the molecules are known. But the ruling is not final and Gilead claims that the patents will be upheld. “Now, since the patent application is rejected in the US, chances for the application getting rejected in India become high and Gilead will be forced to withdraw the application,” a patent attorney told FE.
According to analysts, Cipla will be benefited from the verdict. Cipla is marketing a generic version of tenofovir at a cost of $700 per person per year in India, while Gilead’s tenofovir costs $5,718 per patient per year in developing countries. However, Cipla officials refused to comment citing that the matter was sub judice.
Last year, Gilead signed license agreements with 11 Indian Companies for manufacturing and selling Viread in 95 countries, including India. Cipla, which refused Gilead’s licensing offer, challenged Viread’s validity by filing a pre grant opposition, apart from Delhi Network of Positive People, an NGO. However, Indian firms who entered into agreements with Gilead remain unfazed by the verdict. MM Srinivas Reddy, director, marketing, Hetero Drugs, told FE, “We are not worried at all over the verdict. Gilead has the chance to go for further appeal. Let the final verdict come.”
Gilead sells tenofovir alone and in combination with other drugs like Truvada and Atripla. Taken together, the three HIV treatments generated $3.1 billion in sales last year, according to the company reports. (Source: Financial express)

Why to change US patent system when its best in the world?

For years, Germany has been the world's leading exporter, buoyed by sales of high-end technology. People across the globe have benefited from Germany's life-saving drugs and state-of-the-art machinery, not to mention its unrivaled luxury automobiles.However, a recent effort by the United States to reform its patent system threatens to undermine German innovation and deprive Americans and the world of its benefits.The U.S. patent system has been an integral part of German technological development. American patents have helped spur German dominance in areas such as industrial machinery, chemicals, pharmaceuticals and advanced medical devices. They have also helped preserve the nearly one in four German jobs that are dependent on exports.
Between 2000 and 2005, more than 64,000 German inventions received patents from the U.S. Patent Office - roughly the same number of patents Germany issued to its own citizens.The appeal of the American patent system is not limited to Germans. Last year, the U.S. Patent Office granted more than 94,000 patents to foreign inventors. Activity in the U.S. Patent Office was 50 percent higher than the European patent offices combined.The American system is regarded as the strongest protector of patent rights in the world. Unfortunately, the U.S. Congress is considering "reforming" the system. A bill has already been passed by the House and is under consideration in the Senate. Proposed changes could have potentially devastating consequences to research-based industries, especially the pharmaceutical industry.
Europe's inventors have flocked to the U.S. Patent Office because the European patent system is far inferior to America's. Europe's extended post-grant review procedures and artificially low caps on damages for stolen patents undermine the value of European intellectual property. Other flaws include ineffective and slow prosecution of counterfeit and copyright infringement cases.America has reaped great benefits when foreign inventors use the U.S. patent system. Thanks to the development and innovation spurred by American patents issued to Germans, for example, the two countries have developed a remarkably close trade relationship, which has reinforced their close political ties.
Germany consistently ranks as America's top trade partner in Europe. Moreover, as of 2000, 50 percent of German foreign direct investment went to the United States. Similarly, America was the top investor in Germany. As a direct result of German-American trade, millions of jobs have been created on both sides of the Atlantic.Patent protections will play an even more important role in German-American trade as it becomes increasingly dominated by research-based industries such as pharmaceuticals, chemicals and high-tech machinery. The process of innovation is so costly in these sectors that they cannot survive without strong protection of intellectual property rights.
In the pharmaceutical industry, it takes on average about 10 years and $800 million to develop just one drug. Many attempts lead to dead ends. Of the few drugs that make it to market, more than 50 percent will never turn a profit.To continue the research necessary to develop new drugs, which have been credited with 40 percent of the increase in life expectancy over the past 20 years, drug companies must recoup all their losses on just a handful of drugs. When patent regimes allow generics to flood the market, this becomes impossible.
However, by passing the Patent Reform Act of 2007, Congress would replace many of the best aspects of the U.S. patent system with the worst aspects of the European system. It would hurt the United States, Germany and - in the long run - many consumers worldwide."Virtually all of the inventions which ultimately hastened economic development and lifted living standards - especially new technologies and manufacturing processes - were developed in societies with strong intellectual-property protections," according to a 2005 report, "The Economic Value of Intellectual Property." U.S. patent reform will only weaken international protection of intellectual property.
The patent-reform bill would reduce incentives to perform research and development, threaten jobs at home and abroad and damage trans-Atlantic trade relationships, which have brought wealth and vital goods to the United States and Europe.Congress should think twice before "fixing" a patent system that is the envy of the world.
(This is is an interesting article from GERNOT PEHNELT who is a lecturer of economics and research associate at the Friedrich-Schiller-University in Jena, Germany.)

supreme court stays proceedings before IP Board on Glivec case

The Indian Supreme Court (The Hindu) has stayed proceedings before the Intellectual Property Appellate Board (IPAB), regarding the hearing on the rejected patent application of Novartis’ cancer drug Glivec.
The development follows a Special Leave Petition (SLP) filed by Hyderabad-based Natco Pharma at the apex court, a lawyer familiar with the case told Business Line.
Natco’s SLP at the Supreme Court came after the Madras High Court said in November last year that a two-member bench comprising the Chairman and Vice-Chairman of the IPAB could look into the case. The Madras HC’s ruling seemed to go with the revised approach that the Government had earlier submitted to the court, where the Centre had made a similar suggestion.
The Centre had come up with a revised approach to get the IPAB to hear the rejection of Novartis’ Glivec patent application, after Novartis objected to the composition of the IPAB. The IPAB had former Patent Controller Mr S. Chandrasekaran, on it as a technical member. And Novartis had objected to this as he was head of the Patent Controller’s office when it had rejected Novartis’ application in January 2006.
All parties to the case, including Novartis, the Centre, generic companies like Ranbaxy and Cipla and the Cancer Patients Aid Association will now have to respond to the latest development at the SC within four weeks, the lawyer said.
The development at the Supreme Court on Monday comes even as the IPAB was scheduled to look into the rejection of Givec’s patent application on the same day.
The case on Novartis’ rejected Glivec patent application had shifted from the Madras HC to the IPAB after the latter was created last April, following a notification from the Centre. But the focus again shifted back to the Madras HC, with Novartis objecting to the appointment of the former Patent Controller as technical member on the IPAB. The Madras HC subsequently ruled on the issue late last year, following which Natco approached the apex court.

Merck, Schering-Plough to Cooperate in Vytorin Probe

Jan. 27 (Bloomberg) -- Merck & Co. and Schering-Plough Corp. will cooperate in the probe of Vytorin by New York Attorney General Andrew Cuomo, who wants to know if the pharmaceutical companies hid research on the cholesterol- lowering drug.
Cuomo's investigation focuses on the marketing of the drug and sales of the companies' shares before the negative results were made public, the attorney general's office said yesterday in an e-mailed statement.
A study released Jan. 14 showed that Vytorin, a combination of the drugs Zocor and Zetia which had $5 billion in sales in 2007, may be no more effective at reducing plaque buildup inside the arteries than Zocor alone. New York's Medicaid program for those with low incomes has paid about $21 million for Vytorin in the past two years rather than buying a cheaper generic version that might be at least comparable to the name brand, Cuomo said.
``We are aware of the subpoenas and will cooperate with the New York attorney general,'' said Schering-Plough spokeswoman Rosemarie Yancosek. ``We stand behind our products as we have done nothing wrong.''
``Merck received the subpoenas and will cooperate fully,'' said spokesman Chris Garland. ``Merck stands behind the safety and efficacy profiles of Zetia and Vytorin. We acted with integrity and good faith with respect to the trial.''
Stock Sales
The attorney general also sought information to determine whether insider sales of stock were appropriate and whether statements to investors were accurate. He declined, however, to pinpoint any specific trading in the shares of Merck, based in Whitehouse Station, New York, or Schering-Plough, based in Kenilworth, New Jersey.
Carrie Smith Cox, a Schering-Plough executive vice president, sold 900,000 shares for $28 million on April 20, according to a Securities and Exchange Commission filing. No reference to her was made in yesterday's statement. The company said on Jan. 22 that Cox followed procedures in making the sale.
``We will investigate and, when appropriate, hold accountable drug companies for engaging in irresponsible and deceptive conduct and any deceitful marketing of prescription drugs,'' Cuomo said in the statement.
The company-sponsored study from October 2002 to April 2006 measured the thickness of the carotid arteries of 720 patients with a predisposition to high cholesterol who took the largest dose of Vytorin over two years. A blocked carotid cuts blood supplies to the brain and can cause a stroke.
Lawmakers' Probe
Lawmakers are probing whether Schering and Merck acted improperly in their marketing for Vytorin, which cost an average of $3 a pill compared with 3 cents for Zocor.
Earlier this month, Representatives John Dingell and Bart Stupak, Michigan Democrats, sent letters asking the companies and the U.S. Food and Drug Administration for records related to their marketing of the products.
The FDA, meanwhile, has said it may take six months to accumulate the data from the Enhance trial before a decision can be made on whether to investigate the drug.
New prescriptions for Vytorin have fallen 22 percent and 23 percent for Zetia in the 10 days since the study was reported, according to James Kelly, an analyst with Goldman Sachs Group Inc.

Cypress Reaches Settlement with Glaxo Relating to Ranitidine Oral Syrup Products

Cypress Pharmaceutical, Inc. today announced that it has reached a settlement with Glaxo, part of the GlaxoSmithKline group of companies, resolving all disputes between the companies related to Cypress' generic ranitidine oral solution products and Glaxo's Zantac(R) syrup.
Under the terms of the settlement, Glaxo has agreed not to assert its patent against Cypress' new alcohol-free formulation of its generic ranitidine oral syrup. Cypress expects to launch the product immediately upon receiving FDA approval. As a result of the settlement, the parties filed a stipulation to dismiss their patent litigation pending in the U.S. District Court for the Southern District of New York.

Forest and Merz File Additional Lawsuit Against Generic companies for Patent Infringement of Memantine

Forest Lab, Merz Pharma announced that they have filed a second lawsuit in the U.S. District Court for the District of Delaware against additional companies for infringement of US5061703 (the '703 patent) which covers a method for the prevention or treatment of cerebral ischemia comprising the step of administering, to a patient in need thereof, an effective amount of an adamantane derivative like Memantine hydrochloride. The defendants named in the lawsuit include Dr. Reddy's Laboratories Limited, Genpharm Inc., Interpharm Inc., Mylan Pharmaceuticals Inc., Ranbaxy Laboratories Limited, Sun India Pharmaceutical Industries Limited, and related companies and subsidiaries thereof. The '703 patent expires in April 2010. Forest has applied for patent term extension which, if granted, would extend the '703 patent until September 2013.
As previously reported, Forest and Merz had received notification from several companies that they had filed Abbreviated New Drug Applications (ANDA) with Paragraph IV certifications to obtain approval to market generic versions of Namenda and commenced an action in patent infringement in the U.S. District Court in Delaware against such filers.

New rules for labeling changes for approved drugs

FDA issued (News from fdalawblog) a proposed rule that would “reaffirm [the Agency’s] longstanding position that” labeling changes for approved drugs, biologics, and medical devices may only be made to show newly acquired information or to “add or strengthen a contraindication, warning, precaution, or adverse reaction” when there is sufficient evidence to support the change.
FDA’s current regulations at 21 C.F.R. §§ 314.70(c), 601.12(f), and 814.39(d) allow changes to be made to drug, biologic, and device labeling in certain situations upon FDA’s receipt of a supplemental application, commonly referred to as a “changes being effect supplement,” or a “CBE supplement,” for drugs and biologics, and a Premarket Approval Application (“PMA”) supplement or Special PMA Supplement for devices. (For convenience, we use the term CBE supplement to refer to drug, biologic, and device labeling supplements.) FDA’s proposal, if finalized, would make explicit that CBEs may only be used to update newly acquired safety information, which FDA proposed to define as “data, analyses, or other information not previously submitted to the agency, or submitted within a reasonable time period prior to the CBE supplement, that provides novel information about the product.” For example, if a postmarket study suggests a more severe and significant adverse reaction than previously known, then a CBE supplement “may be appropriate;” but if a study only provides additional data on a known adverse reaction, a CBE supplement would not be appropriate. Further, according to FDA, a CBE supplement may only be used for labeling changes relating to “contraindications, warnings, precautions, or adverse reactions in circumstances when there is sufficient evidence of a causal association with the drug, biologic, or medical device.”
Because FDA’s proposal would merely codify existing FDA policy, it would not significantly alter Agency practice or establish new regulatory requirements. However, the proposed rule, if finalized, could give significant support to firms that invoke an FDA preemption defense in product liability cases where plaintiffs argue that firms should revise their own labeling in accordance with state law. Specifically, by revising its CBE supplement regulations to state that such applications require “newly acquired information,” FDA could limit the number of cases in which the results from certain studies could be used to support a stronger labeling warning and a product liability lawsuit. FDA states in the proposal that:
To the extent that state law would require a sponsor to add information to the labeling for an approved drug or biologic without advance FDA approval based on information or data as to risks that are similar in type or severity to those previously submitted to the FDA, or based on information or data that does not provide sufficient evidence of a causal association with the product, such a state requirement would conflict with federal law. In such a situation, it would be impossible to market a product in compliance with both federal and state law, and the state law would “stand[] as an obstacle to the accomplishment and execution of the full purposes and objectives of Congress,” Hines, 312 U.S. at 67. Moreover, such a state law requirement relating to a medical device would constitute a requirement that is different from, or in addition to, a federal requirement applicable to the device, and which relates to the safety or effectiveness of the device. 21 U.S.C. 360k(a).
Indeed, this is precisely the issue the Supreme Court will consider later this year in Wyeth v. Levine - whether prescription drug labeling preempts state law product liability claims. Documents on the case are available from SCOTUSBlog. Last week, the Court agreed to hear the case.
In 2006, the Vermont Supreme Court ruled against Wyeth concerning the company’s labeling of PHENERGAN (promethazine HCl) and held that the FDC Act “provides a floor, not a ceiling, for state regulation.” FDA has previously stated (pages 3934-35) that “FDA approval of labeling under the [FDC Act] . . . preempts conflicting or contrary State law,” and that “FDA interprets the [FDC Act] to establish both a ‘floor’ and a ‘ceiling,’ such that additional disclosures of risk information can expose a manufacturer to liability under the act if the additional statement is unsubstantiated or otherwise false or misleading.”
FDA has invited comments on the Agency’s proposal regarding when safety information relating to a drug, biologic, or medical device should be considered “newly acquired.” All comments to the proposed rule are due March 17.

USFDA panel gave positive report for Alvimopan

A Food and Drug Administration panel gave a positive recommendation to a gastrointestinal treatment co-developed by GSK giving the drug the inside track to U.S. regulatory approval.
The FDA panel said the benefits of the drug Entereg (Alvimopan), co-developed by Glaxo and Adolor Corp of Pennsylvania, outweigh its risks. The drug treats a condition called post-operative ileus, in which the gastrointestinal system doesn't function properly after bowel surgery.
The condition, which annually afflicts hundreds of thousands of patients, is characterized by constipation and other gastrointestinal dysfunction.
The full FDA is scheduled to make a final decision on Entereg by Feb. 10. The agency is not bound to follow the recommendations of its panels, though it typically does.
The agency might extend its review period, however, because the panel on Wednesday said Adolor needs to come up with a better plan for ensuring that patients don't take the drug on a long-term basis. Safety data show that the drug can be dangerous to the cardiovascular system in the long term, the panel said.

Abbott got $1.2 billion fourth-quarter profit

Pharmaceutical and medical products maker Abbott Lab reported a $1.2 billion fourth-quarter profit Wednesday on the strength of strong drug sales worldwide, capping a year which saw international sales account for a majority of its business for the first time.
Blockbuster anti-inflammatory drug Humira led the way with a 43 percent jump in sales from a year earlier to top $3 billion in sales for 2007. Other Abbott drugs Depakote, TriCor and Kaletra also posted double-digit sales gains as pharmaceuticals helped it increase companywide sales by 16 percent.
Abbott's first-quarter outlook for earnings slightly below analysts' expectations sent its stock down despite the strong quarter. Shares fell $1.21, or 2 percent, to $56.28 in afternoon trading Wednesday.
Both the company and analysts painted an optimistic view of longer-term prospects for the North Chicago, Ill.-based company, however.
"Humira represents the primary growth and profitability driver for the company, and fourth-quarter performance continues to support our bullish view of the product," Cowen and Co. analyst Sara Michelmore said in a note to investors.
The fourth-quarter gain represented a turnaround from a loss a year earlier, when results were reduced by hefty acquisition charges for Kos Pharmaceuticals Inc. For the quarter ended Dec. 31, the company's net income amounted to 77 cents per share and compared with a loss of $476.2 million, or 31 cents per share, in the same period of 2006.
Revenue rose to $7.22 billion from $6.22 billion, exceeding the $6.97 billion estimated by analysts polled by Thomson Financial. Favorable exchange rates contributed 4.5 percent to the increase.
Adjusted earnings, excluding certain items, rose to 93 cents per share from 75 cents per share in the year-earlier period. That was a penny better than analysts' consensus estimate.
The 2006 fourth quarter included a $1.3 billion, or 85 cents-per-share, charge related to costs in the $3.7 billion acquisition of Kos Pharmaceuticals last year.
"Going forward, we're targeting higher growth markets, including emerging markets where we can distinguish Abbott from the competition with leading technology and innovative new products that meet the needs of patients and customers," CEO Miles White said on a conference call. "In 2007, we saw that focus pay off as our unique mix of businesses and new products delivered strong results."
Abbott's U.S. pharmaceutical sales increased 16.6 percent in the quarter and its international pharmaceutical sales rose 21.3 percent.
Humira, Abbott's top-selling product, recorded $527 million in sales in the most recent quarter. The company forecast 2008 Humira sales of about $4 billion.
Medical product sales climbed 11.5 percent, led by 15.2 percent growth in worldwide Diabetes Care sales and a 16.4 percent gain in international diagnostics sales. Nutritional product sales were up 11.2 percent over a year earlier, helped by strong results in emerging growth markets.
Abbott projected earnings per share of $3.20 to $3.25 for 2008 and 61 cents to 63 cents for the first quarter, both excluding items. Analysts had estimated earnings at 65 cents per share for the first quarter and $3.22 per share for the year.
Given the leadership positions of our major businesses, and the new products launching over the next year, we expect another year of strong results in 2008," Chairman and CEO Miles White said in a statement.

New warning for the use of Rosiglitazone

The European Medicines Agency (EMEA) has recommended updating the product information for rosiglitazone-containing antidiabetic medicines. Rosiglitazone is available in the European Union as Avandia (Rosiglitazone maleate), Avandamet (Rosiglitazone maleate/metformin) and Avaglim (Rosiglitazone maleate/Glimepiride).
During its January 2008 meeting, the Agency’s Committee for Medicinal Products for Human Use (CHMP) adopted a scientific opinion recommending the inclusion of a new warning stating that the use of Rosiglitazone in patients with ischemic heart disease and/or peripheral arterial disease is not recommended.
The CHMP also adopted an opinion recommending the addition of a new contraindication stating that rosiglitazone must not be used in patients with an acute coronary syndrome, such as angina or some types of myocardial infarction, because the medicine has not been studied in controlled trials in this specific patient group.
The recommended changes to the product information have been made as a follow-up measure to the re-assessment of the benefits and risks of rosiglitazone and pioglitazone, another antidiabetic medicine. This re-assessment was finalised by the CHMP in October 2007, concluding that the benefits of both medicines continued to outweigh their risks in their approved indications, but that the product information for rosiglitazone should be changed.
Looking more globally at antidiabetic medicines and the cardiovascular risk associated with their use, the CHMP and its Efficacy Working Party are currently re-examining their existing ‘Note for guidance on clinical investigation of medicinal products in the treatment of diabetes mellitus’ to decide whether changes are needed. A concept paper, setting out the main points for revision, is expected to be released in February.

USPTO rejected patent covering tenofovir disoproxil fumarate

The Public Patent Foundation ("PUBPAT") announced today that the USPTO has rejected four key HIV/AIDS drug patents held by Gilead Sciences that relate to the drug known generically as tenofovir disoproxil fumarate (TDF), a key weapon in the battle against HIV/AIDS. Gilead markets TDF in the USA under the brand name VIREAD and as a part of its ATRIPLA combination product.Roughly 40 million people worldwide are infected with HIV/AIDS, including more than 1.2 million Americans. The USFDA will not allow anyone other than Gilead distribute TDF in the United States because Gilead claims the four patents challenged by PUBPAT and now rejected by the Patent Office give them the exclusive right to do so."Every person suffering from HIV/AIDS has a right to get the best medical treatment science can offer, without any unjustified impediments placed in their way," said Dan Ravicher, PUBPAT's Executive Director. "This includes Americans infected with HIV/AIDS, who are entitled to the best pharmaceuticals possible without undeserved patents making them exorbitantly expensive."In its filings challenging the patents, PUBPAT submitted prior art that Gilead had not disclosed to the Patent Office during the patent application process that resulted in the patents being granted to the Foster City, California, biopharmaceutical giant. PUBPAT also described in detail how the prior art would have prohibited the patents from being issued in the first place, had the Patent Office had been aware of it. The Patent Office has now agreed with PUBPAT and found that each of the four Gilead Sciences patents are undeserved. Although Gilead has the right to respond to the Patent Office's rejections of the patents, third party requests for re-examination, like the ones filed by PUBPAT against the four Gilead TDF patents, are successful in causing the reviewed patents to either be revoked or changed more than two-thirds of the time."We are extremely pleased that the Patent Office has agreed with us that Gilead's TDF patents are invalid," said Ravicher. "This means that we are now well on the way towards ending the harm being caused to the public by Gilead's use of the patents to prevent anyone else from offering TDF to HIV/AIDS patients in the United States."The Gilead Sciences TDF patents challenged by PUBPAT that have now been rejected by the Patent Office are US5922695, US5935946, US5977089 and US6043230. Gilead has applied for similar patents on TDF in other countries throughout the world, including India, where they have received fierce opposition by non-profit AIDS patient groups.

USPTO grant contraceptive patent to Barr

Barr Pharmaceuticals, Inc. today announced the U.S. Patent and Trademark Office (PTO) issued US7320969 (which covers a method of contraception in a female in need thereof, the method comprising administering to the female a dosage comprising a combination of estrogen and progestin for a period of 81 to 89 consecutive days, followed by administration of a dosage consisting essentially of estrogen for a period of 2 to 8 consecutive days, wherein the estrogen that is administered in combination with progestin for the period of 81 to 89 consecutive days is administered in a daily amount equivalent to about 10 .mu.g to about 50 .mu.g of ethinyl estradiol, the estrogen that is administered for the period of 2 to 8 consecutive days is administered in a daily amount equivalent to about 5 .mu.g to about 10 .mu.g of ethinyl estradiol, and the progestin that is administered for the period of 81 to 89 consecutive days is administered in a daily amount of about 150 .mu.g of levonorgestrel) for the Company's SEASONIQUE(R) extended- cycle oral contraceptive. The patent will expire on January 30, 2024. The Company also announced that it has submitted the patent to the U.S. Food and Drug Administration (FDA) for issuance in the Orange Book.
"We are very pleased that the PTO has issued this important patent to protect our SEASONIQUE extended-cycle oral contraception intellectual property," said Bruce L. Downey, Barr's Chairman and CEO. "We remain committed to developing new products for our portfolio of extended-cycle oral contraceptives and to providing women with options as they consider their contraceptive alternatives."
The Company received FDA approval for SEASONIQUE (levonorgestrel/ethinyl estradiol tablets 0.15 mg/0.03 mg and ethinyl estradiol tablets 0.01 mg) extended-cycle oral contraceptive in May 2006. SEASONIQUE is indicated for the prevention of pregnancy and represents the next generation of extended-cycle oral contraceptives in a category the Company created with the launch of the SEASONALE extended-cycle oral contraceptive in 2003.

Drug filing/approvals

Teva got tentative approval for Lansoprazole: Teva Pharma announced today that the USFDA has granted tentative approval for the Company's Abbreviated New Drug Application (ANDA) to market its generic version of TAP Pharmaceutical's gastric-acid pump inhibitor, Prevacid(R) (Lansoprazole) Delayed-release Capsules, 15 mg and 30 mg. The brand product had annual sales of approximately $3.4 billion in the United States for the twelve months ended September 30, 2007, based on IMS sales data.Teva is currently in patent litigation concerning this product in the U.S. District Court for the District of Delaware involving Teva's paragraph IV certification to U.S. Patent Nos. 4,628,098 and 5,045,321. A trial was held in November, at the end of which the Court indicated it anticipates it will issue a decision before the June 7, 2008 expiration of the mandatory 30-month stay of FDA approval associated with the patent litigation.
Teva filed Para IV on Fenofibrate: Fournier Lab Ireland Ltd, a wholly-owned unit of Solvay Pharmaceuticals, was informed by Teva Pharmaceuticals that it has filed an ANDA - Abbreviated New Drug Application - with a Paragraph IV certification, seeking the approval of a generic version of TriCor® (Fenofibrate) 145mg NFE tablets in the United States.The Paragraph IV certification procedure challenges a number of US patents relating to TriCor® which run through the next decade.Such procedures are not unusual for branded products in the United States. Fournier Laboratories Ireland Ltd. remains fully committed to its fenofibrate franchise and is currently evaluating its options.
Banner Pharm got approval for Nimodipin: Banner Pharmacaps Inc., a leader in the pharmaceutical industry for the development of soft gelatin dosage form technology, today announced that the USFDA has granted approval for the Company's Abbreviated New Drug Application (ANDA) for Nimodipine 30 mg soft gelatin capsules. Banner's Nimodipine 30 mg capsules are the AB-rated generic equivalent of Bayer's Nimotop(R) 30 mg capsules, and are indicated for the treatment of subarachnoid hemorrhage, a form of cerebral bleed. Banner's product can be dispensed either in blister packaging or in bottles. Banner has partnered with Heritage Pharmaceuticals Inc., an Edison, New Jersey based generics company, for the exclusive US sales and marketing rights for Nimodipine.
USFDA approved Micafungin sodium sNDA: Astellas Pharma Inc. announced today that the USFDA has approved their Supplemental New Drug Application (sNDA) seeking approval for the use of MYCAMINE® (Micafungin sodium) for Injection in the treatment of patients with Candidemia, Acute Disseminated Candidiasis, Candida Peritonitis and Abscesses. MYCAMINE was approved in 2005 for the treatment of patients with esophageal candidiasis and is the only echinocandin approved for the prophylaxis of Candida infections in patients undergoing hematopoietic stem cell transplantation.
NovaDel Pharma filed NDA for zolpidem tartrate Oral Spray: NovaDel Pharma Inc., a specialty pharmaceutical company developing oral spray formulations for a broad range of marketed treatments, announced today that the USFDA has accepted for filing its New Drug Application (NDA) for ZolpiMist(TM) (zolpidem tartrate) Oral Spray for the short-term treatment of insomnia. The company anticipates the FDA will complete its review by the end of the year consistent with PDUFA guidelines. NovaDel submitted its ZolpiMist(TM) application using the FDA's 505(b)(2) process based on data from two randomized, open-label, dose-ranging studies comparing ZolpiMist(TM) with Ambien(R) tablets in young and elderly healthy volunteers. Both studies compared the pharmacokinetics and safety of comparable doses of zolpidem administered as an oral spray versus tablets. The pharmacokinetic profiles were assessed by the maximum drug concentration (Cmax) and total exposure to drug (area-under-the-curve/AUC0-inf). The speed of drug absorption and level of sedation were also assessed in these studies. The results demonstrated bioequivalence between ZolpiMist(TM) and Ambien(R). Also included in the submission were data from process validation and registration stability batches produced at the intended commercial manufacturing facility.
USFDA has approved Colesevelam HCl: Daiichi Sankyo, Inc, said the USFDA has approved its cholesterol drug Welchol (Colesevelam HCl) to reduce both glucose levels and low density lipoprotein cholesterol levels (LDL-C) in adults with type 2 diabetes.

Teva got 180 days exclusivity for Granisetron HCl

USFDA’s requested for public comment to help resolve 180-day exclusivity issues concerning a generic version of the antinauseant and antiemetic drug KYTRIL (granisetron HCl) Injection. Specifically, in October 2007, FDA established a public docket in response to a letter from Teva Parenteral Medicines ("Teva"), in which the company argued that "the plain language and structure of the [FDC Act] compel the conclusion that Teva is entitled to 180-day exclusivity because Teva is the first applicant that submitted a substantially complete paragraph IV ANDA." Earlier today, FDA posted its January 17, 2008 response concluding that Teva did not forfeit 180-day exclusivity. This conclusion had been anticipated, because earlier this month Teva announced the approval of the company’s granisetron HCl ANDA with 180-day exclusivity.At issue in this case are the "failure to market" 180-day exclusivity forfeiture provisions at FDC Act § 505(j)(5)(D)(i)(I) added by the Medicare Modernization Act ("MMA") in 2003. Under these provisions, a generic applicant whose ANDA contains a paragraph IV patent certification and who is a "first applicant" eligible for 180-day exclusivity forfeits eligibility for such exclusivity if the firm fails to market the drug by the later of:(aa) the earlier of the date that is –(AA) 75 days after the date on which the approval of the application of the first applicant is made effective under subparagraph (B)(iii); or(BB) 30 months after the date of submission of the application of the first applicant; or(bb) . . . the date that is 75 days after the date as of which, as to each of the patents with respect to which the first applicant submitted and lawfully maintained a certification qualifying the first applicant for the 180-day exclusivity period under subparagraph (B)(iv), at least 1 of the following has occurred:(AA) In an infringement action brought against that applicant with respect to the patent or in a declaratory judgment action brought by that applicant with respect to the patent, a court enters a final decision from which no appeal (other than a petition to the Supreme Court for a writ of certiorari) has been or can be taken that the patent is invalid or not infringed.(BB) In an infringement action or a declaratory judgment action described in subitem (AA), a court signs a settlement order or consent decree that enters a final judgment that includes a finding that the patent is invalid or not infringed.(CC) The patent information submitted under [FDC Act § 505(b) or (c)] is withdrawn by the holder of the application approved under [FDC Act § 505(b)].In May 2004, Teva submitted the first ANDA to FDA containing a paragraph IV certification for a generic version of KYTRIL. The application also contained a paragraph III certification (date of patent expiration) and a "section viii statement" to a method-of-use patent. Roche, the NDA holder/patent owner, did not sue Teva (or any subsequent ANDA applicant) for patent infringement, and FDA tentatively approved Teva’s ANDA in August 2005. The patent subject to the paragraph III certification expired in December 2007; however, the 30-month period described in FDC Act § 505(j)(5)(D)(i)(I)(aa)(BB) above expired in November 2006.Teva argued that despite the expiration of the 30-month period, the firm remained eligible for 180-day exclusivity, which would be triggered by Teva’s commercial marketing of the drug.Specifically, Teva’s letter states:[T]he plain language and structure of the [FDC Act] compel the conclusion that Teva is entitled to 180-day exclusivity because Teva is the first applicant that submitted a substantially complete paragraph IV ANDA . . . . Teva’s exclusivity has not been forfeited . . . because there is a continuing possibility of ANDA-based patent litigation that could result in a "later" forfeiture event under [FDC Act § 505(j)(5)(D)(i)(I)]. . . .[The FDC Act] requires FDA to determine which is "the later of" (1) a determinate forfeiture trigger . . . "or" (2) a contingent forfeiture trigger . . . . But there is no conceivable way for FDA to determine which of those 2 potential triggers occurs "later" until (a) one of the contingencies that could give rise to a forfeiture trigger [under FDC Act § FDC Act § 505(j)(5)(D)(i)(I)(bb)] has occurred, or (b) none of the contingencies can occur. After all, it is impossible to know whether a contingent event has occurred before it does occur -- and twice as hard to determine that such an event will not occur until it no longer can occur.Teva echoed this argument in the company’s comments submitted to the docket FDA established to solicit public comment on acarbose (PRECOSE) 180-day exclusivity issues.FDA's granisetron docket response agrees with Teva’s argument. FDA states:We find that under the plain language of the statute, 180-day exclusivity is not forfeited for failure to market when an event under subpart (aa) has occurred, but - as in this case - none of the events in subpart (bb) has occurred. The "failure to market" provision results in forfeiture when there are two dates on the basis of which FDA may identify the "later" event as described in section 505(j)(5)(D)(i)(I). The provision does not effect a forfeiture when an event under subpart (aa) has occurred, but no event under subpart (bb) has yet occurred.This is not a situation in which it would be impossible for a later event to occur. Although at the time FDA made its exclusivity decision, there was no litigation regarding the ‘548 patent pending that could result in a forfeiture event under subitem (AA) or (BB) of subpart (bb), there was nevertheless the possibility that either an additional ANDA applicant would be sued as a result of a paragraph IV certification to the patent or one of the applicants would bring a declaratory judgment action against the NDA holder or patent owner. Either of these actions could result in a forfeiture event. In addition, the patent could be withdrawn by the NDA holder, resulting in a forfeiture event under subitem (CC). Because at least one of the events described in subpart (bb) could still have occurred and, if it did, would necessarily occur "later" than December 1, 2006, Teva did not forfeit its exclusivity.FDA also states in a footnote that:Inherent in the structure of the "failure to market" forfeiture provisions is the possibility that a first applicant would be able to enter into a settlement agreement with the NDA holder or patent owner in which a court does not enter a final judgment of invalidity or non-infringement (i.e., without a forfeiture event under subpart (bb) occurring), and that subsequent applicants would be unable to initiate a forfeiture with a declaratory judgment action. This inability to force a forfeiture of 180-day exclusivity could result in delays in the approval of otherwise approvable ANDAs owned by applicants that would market their generic drugs if they could but obtain approval. This potential scenario is not one for which the statute currently provides a remedy. (Source:FDAlawblog)

Pharma news in brief

Pantoprazole Sodium : Teva Pharma announced today that further to its press release dated December 24, 2007, the Company and Wyeth/Altana have agreed to extend their standstill agreement regarding generic Protonix(R) (Pantoprazole Sodium), through January 31, 2008. Under the agreement, Teva agreed not to ship additional product. This extension of the standstill period will allow the parties to continue their patent litigation settlement discussions

Barr in negotiation for patent dispute settlement: Barr Pharma today announced that the Company is in discussions with Ortho Women's Health & Urology, Division of Ortho-McNeil-Janssen Pharmaceuticals, Inc. concerning a definitive agreement to settle the outstanding patent litigation involving Ortho Women's Health & Urology's oral contraceptive product, ORTHO TRI-CYCLEN(R) LO (norgestimate/ethinyl estradiol). The United States District Court for the District of New Jersey has postponed the trial date. The general terms and status of the anticipated settlement will not be disclosed by either party until a definitive agreement is reached.

Teva to aquire CoGenesys: Teva Pharma today announced that it has entered into a definitive agreement to acquire CoGenesys, Inc., a privately-held biopharmaceutical company with a broad based biotechnology platform and focused on the development of peptide- and protein-based medicines across broad therapeutic categories. CoGenesys was established in 2005 as a division within Human Genome Sciences Inc. (HGSI) to focus on early drug development and was spun off as an independent company in June 2006. Teva's existing biotechnology infrastructure includes product development and manufacturing in several countries. The Company also markets a portfolio of biopharmaceutical drugs outside the United States, including interferon alpha 2b, granulocyte colony-stimulating factor ("GCSF") and human growth hormone ("hGH"), while marketing hGH in the United States as well. Under terms of the agreement, Teva will pay a purchase price of $400 million cash, funded from its internal resources. The transaction has been approved by the boards of directors of each company and by the shareholders of CoGenesys and is subject to customary closing conditions (including approval under the Hart-Scott-Rodino Antitrust Improvements Act of 1976), and is expected to close during the first half of 2008.

Orphan drug status: Marshall Edwards announced today that its triphendiol (previously known as NV-196) has been granted orphan drug status by the U.S. Food and Drug Administration (FDA) for the treatment of pancreatic cancer and for the treatment of cholangiocarcinoma, or bile duct cancer. An orphan drug refers to a product that is intended for use in a disease or condition that affects fewer than 200,000 individuals in the United States. A grant of orphan drug status provides 7 years of market exclusivity for the orphan indication after approval by the FDA, as well as tax incentives, study design assistance, and eligibility for grant funding from the FDA during its development.

Merck V/S Arrow: Alendronate sodium trihydrate (Europe)

In a significant decision in Arrow v Merck the Court has held that a generic drug company could request a declaration that its product was obvious at the priority date of a patent application. If so, were the patent granted from that application to cover the product it would be invalid. The decision therefore opens up the possibility of generic companies (and any other would-be infringer) being able to clear a product’s path to market without having to wait for a patent to grant in order to bring invalidity or non-infringement proceedings.
In 2003, the English Court of Appeal revoked Merck’s EP998292 Patent (‘292), which covers method to treat osteoporosis patients with 70mg alendronate sodium trihydrate over a week, rather than 10mg once a day, on grounds of obviousness and lack of novelty, and because it was, in substance, a method of treatment of the human body by therapy. In 2004 the Opposition Division of the EPO revoked the same patent, and in 2006 the Technical Board of Appeal dismissed an appeal, finding the patent invalid for added matter. The Board did not consider arguments of obviousness and lack of novelty.
Alendronate preparations were first sold in 1995, with a 10mg oral formulation being introduced in 1997. In 1998, (priority date 22 July 1997) Merck applied for a 70mg once a week formulation, that patent (’292) being revoked by Arrow Teva and Generics (UK) in 2003, for lack of novelty, lack of inventive step, and because it was a method of treatment of the human body by therapy. That decision was upheld by the Court of Appeal in November 2003.
Following revocation of the ‘292 Patent, Arrow and other generic companies sold the 70mg product throughout Europe, the markets have become generic, and the cost of a 4 x 70mg pack has fallen from around £15-£18 to around £1-£2, no doubt resulting in a very substantial loss of revenue to Merck. During the course of prosecution of the ’292 Patent, Merck filed four divisional applications. These applications were stayed during the ’292 Patent opposition proceedings, but revived on the conclusion of those proceedings.The Examining Division of the EPO has found one of these divisional applications to be inventive, and allowed it to proceed to grant, as EP1175904 (“’904”). Claim 1 of ’904 is a “Swiss claim” directed to the use of alendronate to make a medicament for the treatment of osteoporosis in the human, where the medicament is orally administered as a unit dosage comprising about 70mg of alendronate, according to a continuous schedule having a once weekly dosing interval. The key idea therefore appears to be essentially the same as that of the ’292 Patent, namely to give osteoporosis patients 70mg of alendronate once a week.The Examining Division has justified this change in position, on the basis of the declaration by a Dr. Goldberg of Merck, which apparently gives details of the statistically significant effect arising from administration of 70mg of alendronate once a week, rather than a once a day 10mg tablet.
As the judge noted, Arrow v Merck was an exceptional case. Arrow had cleared the path for its generic version of Merck’s Fosamax by successfully applying to the court for revocation of Merck’s relevant European patent (UK) in 2003. The European Patent Office (EPO) also revoked the patent in opposition proceedings. Arrow then proceeded to build up substantial sales in the EU for its drug only for Merck to be granted a second European patent earlier this year, based on the same application as the revoked one, with several more patents that might follow and all of which Arrow potentially infringed as they contained similar claims to the revoked patent. Further Merck clearly intended to enforce its rights and refused to give undertakings not to sue Arrow and to withdraw the UK designations of the applications.
The court evidently sympathised with Arrow’s position. While it could not give the declarations that Arrow actually sought – as they involved the validity of non-UK designations of Merck’s patent and applications over which the High Court had no jurisdiction – the judge decided that the court could rule on whether Arrow’s alendronate (formulated as a sodium salt in a weekly dosage form) was obvious as at the priority date of the patent and applications. If obvious, then any patent that covered the product would be obvious too and so invalid.
This approach neatly avoided the limited circumstances in which declarations of invalidity of patents can by brought under the Patents Act 1977 and which Merck argued formed a complete bar to the relief sought by Arrow.
But more significant is the court’s view that businesses need commercial certainty in patent matters, as in any other, and that the court should assist in providing it where it properly could. In particular Merck’s applications could take a further year or more to be granted as patents during which time Arrow would be accumulating substantial potential liability if it infringed them. Merck could have avoided this effect on Arrow by giving the undertakings but it did not so there was a valid and valuable commercial purpose to the declaration for Arrow. This decision gives a potentially attractive additional tool to declarations of invalidity and non-infringement of patents for those wanting to establish whether or not they infringe a patent and, if there is a risk they do, to clear the path for bringing their product to market. Particularly useful is that, as the declaration on a product can be sought as soon as a patent application is published rather than having to wait for grant, a favourable declaration allows considerably earlier entry on to the market. The decision will therefore be of obvious interest to generics drugs companies though, as it is not being appealed, it needs to be seen whether judges in other cases will follow it, or decide it is restricted to its facts or to exceptional circumstances only, before its full potential can be assessed. (Source :Arrow v Merck [2007] EWHC 1900 (Pat), Anna McKay, Ralph Cox)

Ranbaxy and Dr Reddy settled patent disputes with innovators

Ranbaxy Laboratories Ltd and Dr Reddy’s Laboratories Ltd, India’s top two drug makers, will launch versions of a migraine drug grossing $985 million, or Rs3,891 crore, for GlaxoSmithKline towards the expiry of the patent on the medication, potentially earning profits of up to Rs540 crore more in 2009.
Ranbaxy on Monday said it had settled a lawsuit with the British patent holder GSK, and will enjoy a six-month market monopoly in the US, beginning December. Dr Reddy’s had said in October 2006 that it had been signed on by GSK as the authorized generics partner on Imitrex (sumatriptan succinate), the migraine drug whose patent expires in February 2009.
The Gurgaon drug maker could earn between $80 million and $90 million in the six month exclusivity period, while Dr Reddy’s could earn anything from $22-46 million. Analyst believe that Ranbaxy will earn more profit in comparison to DRL.

It was not immediately clear if Monday’s settlement by Ranbaxy was exclusive or it would share the period with a US unit of Cobalt Pharmaceuticals Inc., an Ottawa-headed firm with which GSK had settled a similar case in November 2006. A Ranbaxy spokesperson insisted the firm would enjoy a full exclusivity period for sumatriptan succinate (the chemical name of Imitrex) for 25mg, 50mg and 100mg strengths.
Monday’s development is similar to a market situation involving the two drug makers and Merck and Co. Ranbaxy, as the patent challenger on Merck cholesterol drug Zocor, had earned revenues of $60 million and Dr Reddy’s, as Merck’s partner for Zocor and prostrate cancer drug Proscar, had grossed $400 million in sales.
In an unrelated development, Dr Reddy’s on Monday said it had settled with Novartis AG not to introduce generic variants of Alzheimer’s drug Exelon that grossed the Swiss drug maker $199 million in 2006. Terms of the settlement were not disclosed.

ExelonÒ (rivastigmine tartrate) is a reversible cholinesterase inhibitor and is known chemically as (S)-N-Ethyl-N-methyl-3-[1-(dimethylamino)ethyl]-phenyl carbamate hydrogen-(2R,3R)-tartrate.Exelon Capsules contain rivastigmine tartrate, equivalent to 1.5, 3, 4.5 and 6 mg of rivastigmine base for oral administration. Inactive ingredients are hydroxypropyl methylcellulose, magnesium stearate, microcrystalline cellulose, and silicon dioxide. Each hard-gelatin capsule contains gelatin, titanium dioxide and red and/or yellow iron oxides.

Vioxx settlement

More than 3,000 former users of Merck & Co's withdrawn Vioxx pain drug have already signed up to take part in a $4.85 billion settlement deal that a federal judge on Friday declared was in the best interests of both sides.
Attorneys for Merck and plaintiffs who claim to have been harmed by Vioxx were in U.S. District Court to give a status report on the settlement to Judge Eldon Fallon, who had presided over all federal Vioxx trials and is overseeing the settlement process.
A total of 57,167 potential participants have registered claims by this week's deadline and 3,065 have already opted to enroll in the settlement, which was announced in November.
Registrants will be divided into Vioxx users who had suffered heart attacks and those who suffered strokes after taking the pain medicine. Merck needs 85 percent of registered plaintiffs in each category to sign on to the settlement for the deal to move forward.
"We continue to expect to meet and exceed the enrollment thresholds, but we don't know when that will occur," said Ted Mayer, an outside counsel for Merck.
There are a series of enrollment deadlines over the coming months with a final opt-in date of October 30, a spokesman for Merck's legal team said.
Asked the most important thing to come out of Friday's hearing, Mayer said: "We have over 57,000 claims submitted for registration and that the enrollment process is underway."

FDA sued over Depakote

On January 14, 2008, Nu-Pharm Inc., a Canadian drug company formerly owned by Apotex, Inc., filed a complaint in the U.S. District Court for the District of Columbia against FDA seeking declaratory and injunctive relief with respect to the company’s Abbreviated New Drug Application ("ANDA") for divalproex sodium delayed-release 500 mg tablets. The drug is marketed by Abbott Laboratories under the trade name DEPAKOTE for the treatment of mania, migraine, and epilepsy, and was first approved in 1983 under NDA #18-723.According to the complaint, Nu-Pharm submitted ANDA #77-615 to FDA in March 2005 with paragraph IV certifications to two Orange Book-listed patents covering DEPAKOTE: U.S. Patent #4,988,731 ("the ‘731 patent") and #5,212,326 ("the ‘326 patent"). These patents are scheduled to expire on January 29, 2008; however, in December 2007, FDA granted Abbott pediatric exclusivity for the drug, thereby delaying generic approval under certain circumstances until July 29, 2008.Earlier, Abbott sued Nu-Pharm in the U.S. District Court for the Northern District of Illinois (Eastern Division) for infringement of both patents, thereby triggering a 30-month stay of approval of Nu-Pharm’s ANDA. According to Nu-Pharm, the 30-month stay expired on November 13, 2007, without any substantive merits ruling on patent infringement. Nu-Pharm then contacted FDA requesting that the Agency grant final ANDA approval.According to the complaint, in December 2007, FDA informed Nu-Pharm that the Agency would not grant final approval based on an order entered in a contempt proceeding in the U.S. District Court for the Northern District of Illinois (Eastern Division) in Abbott Labs v. Apotex. In that proceeding, the charged conduct was the submission of repetitive ANDAs by Apotex and Nu-Pharm to FDA for generic DEPAKOTE. In October 2007, the U.S. Court of Appeals for the Federal Circuit reversed the district court’s judgment of contempt "because the district court erred in finding Apotex in contempt when the conduct at issue was not within the express terms of the injunction." By way of background, in previous paragraph IV patent litigation in that case concerning Apotex’s ANDA #75-112 for generic DEPAKOTE, Judge Richard Posner, sitting by designation in the U.S. District Court for the Northern District of Illinois, ruled that Apotex’s product infringed the ‘731 and ‘326 patents, enjoined the company from manufacturing, using, selling, or offering to sell generic divalproex sodium, and stated that the effective date of approval of ANDA #75-112 would be no earlier than January 29, 2008 when the patents expire - without pediatric exclusivity. The decision was affirmed in 2005. Apotex subsequently entered into an agreement with Nu-Pharm under which Apotex would pay for the costs associated with preparing and submitting a new ANDA (i.e., ANDA #77-615) for generic DEPAKOTE and Nu-Pharm would take on the "litigation risks" arising from the submission of the ANDA.According to the Nu-Pharm complaint, FDA orally refused to grant final approval for ANDA #77-615 on January 9, 2008. Considering FDA’s decision to be final agency action, the company filed a complaint. Nu-Pharm alleges that FDA’s refusal to approve the company’s ANDA violates the FDC Act and the Administrative Procedure Act because "FDA’s decision violates the plain and unambiguous language of the [FDC Act], which provides that FDA shall immediately approve an ANDA where, as in this case, the applicable 30-month stay has expired" and there has been no finding of infringement or validity, and that FDA "has no lawful basis or authority to withhold final approval . . . based on a court order in a wholly separate contempt proceeding to which Nu-Pharm was not a party."(Source FDAlawblog)

Pharma news in brief

1. Aurobindo Pharma Ltd has received an approval from the USFDA to market its 300mg cefdinir capsules in the US market. This is company's 62nd ANDA approval. The drug falls under the anti-bacterial segment and is a generic equivalent of Abbott Laboratories' Omnicef. Earlier, the company also received the final approval for 125 mg/5 mL and 250 mg/5 mL oral suspension of this drug from the US FDA.
   
2. Daiichi Sankyo, Inc., announced today that the United States Food and Drug Administration (FDA) has approved Welchol(TM) (colesevelam HCl) to improve glycemic control (measured as hemoglobin A1C) in adults with type 2 diabetes mellitus in combination with metformin, sulfonylureas, or insulin, either alone or in combination with other anti-diabetic agents. Welchol is now the first and only medication approved to reduce both glucose levels and low density lipoprotein cholesterol levels (LDL-C). The ADA estimates that 20.8 million people in the United States have diabetes with more than 90 percent of these people having type 2 diabetes.(1) Forty percent of patients with type 2 diabetes also have high LDL-cholesterol.(2) Welchol is a new option that addresses both these chronic health conditions and provides physicians with a unique therapeutic approach for treating patients with type 2 diabetes
3. Cipla (News from blog site patent circle) has finally launched a generic onslaught on anti-cancer patented drug Tarceva and reported to be convinced that Tarceva is not patentable and has strong case to oppose despite patent granted in India. Following the generic launch, Roche has filed an infringement case against Cipla in the Delhi High Court, which came up for its first hearing on Friday. Cipla launched generic Tarceva at Rs. 1600 compared to Roche Rs. 4800 per tablet.Erlotinib hydrochloride, an active ingredient of Tarceva is granted Indian Patent No. 196774 (the ‘774 patent) by the Delhi Patent Office against the mail-box Application No. 537/DEL/1996 filed March 13, 1996. Under section 25(2) of the Patents Act 1970, the ‘774 patent statutorily can be opposed within one year from the date of grant of patent, which Cipla may likely consider opting for. Interestingly, Hyderabad-based generic company Natco filed a pre-grant opposition against the Tarceva mail-box Application but subsequently rejected by the Delhi Patent Office. According to Dr. Gopakumar Nair, “Erlotinib is a derivative of another known cancer drug gefitinib, a pre-1995 invention of European drug maker AstraZeneca. Since the Delhi Patent Office had denied a patent for this drug, a patent for its derivative will not be strong, and the generic company can get the patent revoked through a post-grant opposition.” Under section 25(2) the ‘774 patent can be opposed on any of the eleven grounds
   - wrongfully obtained the invention,- prior publication,- subject-matter claimed in already claimed in patent of earlier priority,- publicly known or publicly used in India before the priority date,- obvious and does not involve inventive step,- not patentable subject-matter under the Act,- lack sufficient and clear description of the invention, or method by which it is to be performed,- filed not within 12 months from the priority date,- failure to disclose information under section 8 of the Act,- fail to disclose or wrongly disclose the source and geographical origin of biological material used in the invention, and- anticipated having regard to the knowledge, oral or otherwise.
4. Ranbaxy succeded in invalidating enatiomer (On 10th January 2008) patent of Pfizer in Germany. The basic patent covering Atorvastatin still stands and there will be no change in marketing status of Lipitor in Germany.

Ranbaxy settle sumatriptan succinate patent dispute with GSK

Ranbaxy Laboratories Ltd has settled all matters relating to possible patent litigation with GlaxoSmithKline relating to sumatriptan succinate tablets, the generic version of GlaxoSmithKline's Imitrex tablets.The terms of the settlement, provide that Ranbaxy may distribute a generic version of sumatriptan succinate tablets (in the 25 mg, 50 mg and 100 mg strengths) in the US with an expected launch date in December, 2008. Additional terms of the settlement agreement were not disclosed.The annual market sales for sumatriptan succinate (Imitrex®) were USD 985 million.

AstraZeneca initiated infringement suit against generic S-omeprazole of DRL

AstraZeneca Has filed a lawsuit against Dr. Reddy's Laboratories For the Infringement of US 5,714,504 (which covers composition), US6,875,872 (which covers Compounds,), and US6,369,085 (which covers Form of S-omeprazole) following a paragraph IV certification as part of DRL's filing of an ANDA to manufacture a generic version of AstraZeneca's Nexium® .In a complaint filed Thursday in the U.S. District Court for the District of New Jersey, AstraZeneca alleged that the Indian generic maker’s ANDA to the USFDA for 20 mg and 40 mg delayed release esomeprazole magnesium caplets infringes its Nexium patents.According to AstraZeneca’s complaint, Dr. Reddy’s ANDA seeks to market its esomeprazole magnesium products before the expiration of AstraZeneca’s patents, US5714504; US6875872 and US6369085, thus infringing the patents.AstraZeneca claims that Dr. Reddy’s is required to submit to the FDA specific reasons why its generic product will not infringe AstraZeneca's patents. Dr. Reddy’s has failed to meet this requirement, the complaint said.In December, AstraZeneca asked Dr. Reddy’s to supply more information and samples of its generic product so that the drug maker could determine whether the proposed product would infringe its patents.“DRL refused to agree to timely provide AstraZeneca sufficient access to all of the requested documents, information and samples and instead offered to produce only selected portions of DRL’s ANDA Number 78-279 and certain finished product samples,” the complaint said.AstraZeneca filed the suit in part “to employ the judicial process and the aid of discovery” to determine whether Dr. Reddy's proposed generic esomeprazole magnesium will infringe its three patents, according to the complaint.AstraZeneca is seeking a permanent injunction barring Dr. Reddy’s from marketing an infringing product, court costs and attorneys’ fees.In November 2005, the company asserted the three patents and others against a slew of generic makers, including Ranbaxy Pharmaceuticals Inc., Ivax Corp. and Teva Pharmaceuticals Industries Ltd. That case is still pending the New Jersey District Court.AstraZeneca also faced challenges to Nexium from competitors in Europe. But in November, the European Patent Office reportedly ruled that a patent covering Nexium was still valid in its amended form despite challenges from four generic competitors.In December 2006, the EPO said it had revoked the substance-of-matter patent, which was not set to expire until 2014, following an appeal from Ratiopharm.Nexium is a slightly revised form of Prilosec, another AstraZeneca blockbuster heartburn drug. It is also one of the world’s top-selling drugs, with global sales of $2.62 billion in the first half of 2007.

Innogenetics won infringement suit against Abbot on Hepatitis C Virus genotyping technology

Innogenetics announced that the United States Court of Appeals for the Federal Circuit yesterday evening has affirmed the U.S. District Court’s finding that Abbott Lab infringed Innogenetics’ patented Hepatitis C Virus (HCV) genotyping technology. The Federal Circuit also upheld the jury’s finding that Abbott pay Innogenetics damages for infringement and sanctions for making a baseless claim against Innogenetics, estimated to total approximately $US10 million.
In a decision i the Federal Circuit rejected a myriad of issues raised by Abbott in Abbott’s effort to overturn the unanimous jury verdict in Innogenetics’ favor. The Federal Circuit also affirmed the district court’s finding that Abbott should be sanctioned and pay Innogenetics’ attorneys fees related to Abbott’s baseless claim that Innogenetics had acted improperly in obtaining its US HCV genotyping patent. The result of the Federal Circuit decision is that Abbott must pay an estimated $US 10 million in damages to Innogenetics, using current exchange rates. During the appeal, Abbott challenged many of the rulings made by both the district court and the jury. In rejecting Abbott’s challenges, the Federal Circuit affirmed the district court’s finding that Abbott infringed claims 1, 2 and 3 of Innogenetics’ HCV genotyping patent; dismissed all challenges to the validity of claims 2 and 3 of the patent; affirmed the jury’s damages award; affirmed the district’s finding that the patent is enforceable; and affirmed the district court’s sanctioning of Abbott by ordering it to pay Innogenetics’ attorneys fees resulting from Abbott’s baseless assertion that the patent was not enforceable due to Innogenetics’ conduct before the United States Patent Office.
The Federal Circuit reversed the district court’s decision to summarily rule on the validity of one of the patent’s claims in light of one piece of prior art; finding instead that the district court should have allowed that question to be decided by a jury. The Federal Circuit thereby remanded this issue back to the district court. Importantly, because two of the three claims found to be infringed are unaffected by this ruling, this reversal will not affect either the determination that Abbott infringed Innogenetics’ HCV genotyping patent or the jury’s determination that Abbott must pay damages for its infringement. In reversing the district court’s permanent injunction against Abbott, the Federal Circuit replaced the permanent injunction against Abbott with a compulsory license requiring Abbott to pay Innogenetics a royalty on each future infringing product sold by Abbott in the United States, or made by Abbott in the United States and exported for sale worldwide. The Federal Circuit left it to the district court to precisely determine the amount of damages to be paid to Innogenetics, taking into account accrued interest and the increased value of the Euro. These proceedings also will result in the establishment of an appropriate future royalty payment that Abbott must pay to Innogenetics if it sells any more infringing HCV genotyping assays.
In September 2005, Innogenetics sued Abbott Laboratories alleging that Abbott was infringing the company’s US5846704 (“the ‘704 patent”), which covers a method of genotyping the Hepatitis C Virus. The court found the patent was infringed as a matter of law. On September 1, 2006, a jury returned a unanimous verdict for Innogenetics that the ‘704 patent was valid in all respects. On September 8, 2006, the same jury unanimously found that Abbott’s actions had been willful, and directed Abbott to pay Innogenetics $7 million in damages related to the infringement up to the time of the trial. On January 4, 2007, the judge in this case dismissed Abbott’s requests for a new trial, affirmed the jury’s finding that Abbott infringed the patent, that the patent was valid in all respects and approved the award of $7 million in damages. The judge overturned the jury’s unanimous finding that Abbott’s infringement had been willful. On January 10, 2007, the judge affirmed Innogenetics’ request for a permanent injunction against Abbott, enjoining Abbott from any further sales, use or export of products, including components, that infringe on Innogenetics’ patented genotyping technology. On January 15, 2007, Abbott filed an appeal of the district court case with the United States Court of Appeals for the Federal Circuit. Innogenetics filed a cross-appeal on January 24, 2007. On October 1, 2007, oral argument was held before a three-judge panel of the United States Court of Appeals for the Federal Circuit.

Teva got approval for generic Pravastatin 80 mg tablets

Teva Pharma announced today that the USFDA has granted final approval for the Company's Abbreviated New Drug Application (ANDA) for Pravastatin Sodium Tablets, 80 mg.
Teva's Pravastatin Sodium Tablets, 80 mg are the AB-rated generic equivalent of Bristol-Myers Squibb's Pravachol 80 mg tablets, and are indicated for treatment of certain hyperlipidemias and the primary prevention of coronary events. Teva is already marketing the 10 mg, 20 mg and 40 mg strengths of this product (teva was first Para IV filer and it fought back its exclusivity from FDA).

Lack of new drugs sparked EU raids

European Union antitrust regulators said yesterday that they are raiding pharmaceutical companies in a probe into why so few new medicines and drug makers are emerging.
EU antitrust chief Neelie Kroes said she is looking at the entire pharmaceutical industry and wants to know why generic drugs were so slow to be launched in Europe. Generic medicines are made by other companies after the original developer of the drug loses its exclusive patent rights.
The European Commission said it is conducting inspections at the European premises of a number of pharmaceutical makers - both research-based and generic - including some based outside Europe.
U.S.-based Pfizer, Britain's GlaxoSmithKline and Sanofi-Aventis of France - the world's three biggest drug makers - along with Anglo-Swedish AstraZeneca, Merck Sharp & Dohme, Johnson & Johnson's Belgian unit, U.S.-based Wyeth, and Sandoz International GmbH, the generics division of Swiss company Novartis, confirmed that they had been the target of surprise raids and were co-operating with regulators.
Ms. Kroes said the EU is working closely with U.S. officials - "we're not the only one active in this," she said.
The EU executive will examine whether companies were deliberately preventing new firms from entering the market by abusing patent rights and launching "vexatious litigation" to ward off potential rivals.
It said the probe was partly triggered by its 2005 case against AstraZeneca in which the company was fined €60-million ($90-million) for filing misleading information to patent offices to delay generic versions of its ulcer drug Losec for most of the 1990s.
Fewer new medicines are reaching the market, regulators said, one sign that competition may not be working.
Europe spends €200-billion on medicines every year, or €400 per person.
Most of that cost is carried by state health insurance programs.
Pharmaceutical companies have argued that EU action to restrict patents would cost them billions of euros worth of research and development invested in new drugs, which get little or no return if cheaper generic drugs are allowed on the market.

Impax filed lawsuit against Medicis for generic minocycline hydrochloride extended-release tablets

IMPAX Lab announced that it has filed a lawsuit against Medicis Pharmaceutical Corporation in the United States District Court for the Northern District of California requesting a declaration that IMPAX does not infringe any valid claims of US5908838 (which covers A method for the treatment of acne using tetracycline antibiotic) related to IMPAX's filing in October 2007 of an Abbreviated New Drug Application (ANDA) for minocycline hydrochloride extended-release tablets, a generic version of Solodyn(R).IMPAX's ANDA does not contain any patent certification under Paragraph IV of the Hatch-Waxman amendments because no patents for the SOLODYN(R) product are listed in Approved Drug Products with Therapeutic Equivalence Evaluations (commonly known as the Orange Book), published by the U. S. Food and Drug Administration. Certain antibiotic products are not subject to these Hatch-Waxman procedures and, therefore, do not have patents listed in the Orange Book and are not subject to the patent certification requirements.Medicis Pharmaceutical Corporation markets SOLODYN(R) tablets for the treatment of inflammatory lesions of non-nodular moderate to severe acne vulgaris in patients 12 years of age and older. U.S. sales of SOLODYN(R) tablets were approximately $216.7 million in the 12 months ended November 30, 2007.

Pharma news in brief

• UCB announced today that the New Drug Application (NDA) for the use of Keppra XR(TM) (levetiracetam) extended- release tablets in the adjunctive treatment of partial onset seizures in adults with epilepsy has been accepted for filing by the U.S. Food and Drug Administration (FDA).

• The European Medicines Agency (EMEA) has been formally notified by Marvel LifeSciences Ltd of its decision to withdraw its applications for a centralised marketing authorisation for the medicines Insulin Human Rapid Marvel, Insulin Human Long Marvel and Insulin Human 30/70 Mix Marvel.

• The Reyataz (atazanavir) package insert was revised to include information regarding the administration of atazanavir and/or atazanavir/ritonavir with food, proton pump inhibitors, H2 receptor antagonists, acetaminophen, and fluconazole. Additionally, dosing information in patients with renal impairment was included

• USFDA has issued a public health advisory to alert patients and healthcare professionals about important safety information concerning the drug Edetate Disodium. There have been cases where children and adults have died when they were mistakenly given Edetate Disodium instead of Edetate Calcium Disodium (Calcium Disodium Versenate) or when Edetate Disodium was used for "chelation therapies" and other uses that are not approved by the FDA. As a result, FDA is reviewing the benefit/risk profile of Edetate Disodium to determine if the benefits for its intended use continue to outweigh the serious risks.

• Dr Reddy's Laboratories Ltd has launched Supanac (Diclofenac potassium immediate release 50 mg tablets) in India, increasing its offering in the Rs 2700 crore ( $688 million) NSAID market.

• Pfizer Inc and Scil Technology GmbH (Scil) have signed a licensing agreement with Scil Technology GmbH (Scil) to develop and commercialise CD-RAP, Scil's cartilage specific growth factor. Under this agreement, Pfizer will obtain a worldwide exclusive license to develop and commercialise CD-RAP. In addition to receiving royalties on the sale of any products that may be commercialised under this agreement, Scil is eligible for upfront and milestone payments of approximately US $250 million depending on the achievement of various development and regulatory milestones.

• Nycomed announced today that the Food and Drug Administration (FDA) approved Alvesco(ciclesonide) Inhalation Aerosol in the United States for the maintenance treatment of asthma and as prophylactic therapy in adult and adolescent patients aged 12 years and older. ALVESCO(R) is an inhaled corticosteroid with novel release and distribution properties. Commercialisation and marketing of ALVESCO(R) will be achieved through a U.S. commercial partner.

• Teva Specialty Pharmaceuticals, the U.S. respiratory therapy unit of Teva Pharmaceutical Industries Ltd. (Nasdaq: TEVA) and UCB (Euronext: UCB) today announced an agreement to co-commercialize Teva's U.S. respiratory medicines. The initial product to be jointly promoted in the U.S. is Teva's ProAir(R)HFA (albuterol sulfate) Inhalation Aerosol. ProAir(R)HFA is the number-one branded hydrofluroalkane (HFA) albuterol sulfate inhaler in the U.S. Additionally, the agreement will provide UCB future joint promotion opportunities with other products in development by Teva Specialty Pharmaceuticals. Financial terms of the agreement were not disclosed.

• Dynogen Pharmaceuticals, Inc. today announced that the Company has acquired from Arachnova Therapeutics, Ltd. all of its worldwide patent rights and know-how related to DDP225 in an asset purchase agreement. The Arachnova patent rights, which include granted patents and pending applications related to the use of DDP225 for the treatment of functional bowel disorders, genitourinary (GU) disorders and pain, complement and enhance Dynogen's existing extensive worldwide patent estate related to DDP225. Financial terms of the agreement were not disclosed.

Hi-tech Pharma got final approval of fluticasone propionate nasal spray

Hi-Tech Pharma announced today that the USFDA has granted final approval to the Company's Abbreviated New Drug Application (ANDA) for fluticasone propionate nasal spray, 50mcg. Hi-Tech's fluticasone propionate nasal spray is the AB-rated generic equivalent of GlaxoSmithKline's Flonase(R), which is used in the management of the nasal symptoms of seasonal and perennial allergic and non-allergic rhinitis. Sales of branded and generic fluticasone propionate nasal spray, 50mcg was over $700 million for the 12 months ended June 2007 according to IMS sales data. Hi-Tech will begin immediate shipment of fluticasone propionate nasal spray, 50mcg.

More profit for Forest Lab due to Escitalopram and Memantine hydrochloride

Forest Lab (In a press release) said third- quarter profit rose 21 percent on higher sales of its top- selling drugs, the antidepressant Lexapro (Escitalopram) and Namenda (Memantine hydrochloride) for Alzheimer's disease, products nearing generic competition.
Net income in the fiscal quarter ended Dec. 31 climbed to $301.8 million, or 96 cents a share, from $250.3 million, or 78 cents, a year earlier, the New York-based drugmaker said today in a statement. Earnings beat analysts' estimates, and the company raised its forecast for the year.
Revenue in the quarter rose 12 percent to $998.2 million. The company was expected to bring in $944.1 million, according to the average estimate of 24 analysts surveyed. Research and development spending fell 3 percent to $108.2 million, partly because Forest disbursed less in milestone payments to partners.
``We find it extremely encouraging that Forest can hold down costs and still generate upside to revenue -- demonstrating high profitability and lots of flexibility for future investment in its pipeline,'' said Corey Davis, an analyst at Natixis Bleichroeder in New York, in a note to clients today. He recommends buying Forest shares.
Lexapro sales rose 11 percent to $603.5 million, largely because wholesalers held more inventory at the end of the quarter. Sales of Namenda climbed 26 percent to $218.7 million. Revenue from the blood-pressure drug Benicar, which Forest co- promotes with Japan's Daiichi Sankyo Co., increased 34 percent to $51.8 million.
Higher-than-expected drug sales prompted Forest to boost its forecast for earnings in the fiscal year ending March 31. The company now expects profit in the range of $3.35 to $3.45 a share, excluding 15 cents a share in licensing costs from the second quarter, Forest said today. That's 25 cents higher than the company's Oct. 16 forecast.
The company plans to introduce Bystolic, a new blood- pressure medicine, this month. Forest and partner Cypress BioScience Inc. applied in December to U.S. regulators for approval of the experimental fibromyalgia treatment milnacipran.

First Time Generics December 2007

1 FOMEPIZOLE INJECTION 1 G/ML
PHARMAFORCE, INC.
ANTIZOL INJECTION
12/14/2007

2 EXTENDED PHENYTOIN SODIUM CAPSULES, USP 30 MG
WOCKHARDT LIMITED
DILANTIN (EXTENDED PHENYTOIN SODIUM CAPSULES)
12/18/2007

3 CETIRIZINE HYDROCHLORIDE TABLETS, (OTC), 5 MG AND 10 MG
MYLAN PHARMACEUTICALS, INC.
ZYRTEC ALLERGY TABLETS/ZYRTEC HIVES RELIEF TA
12/27/2007

4 CETIRIZINE HYDROCHLORIDE TABLETS, (OTC), 5 MG AND 10 MG
CARACO PHARMACEUTICAL LABORATORIES, LTD.
ZYRTEC ALLERGY TABLETS; ZYRTEC HIVES RELIEF T
12/27/2007

5 CETIRIZINE HYDROCHLORIDE TABLETS, (OTC) 5 MG AND 10 MG
PAR PHARMACEUTICAL, INC.
ZYRTEC ALLERGY TABLETS/ZYRTEC HIVES RELIEF TA
12/27/2007

6 CETIRIZINE HYDROCHLORIDE TABLETS, (OTC) 5 MG AND 10 MG
RANBAXY LABORATORIES LIMITED
ZYRTEC ALLERGY TABLETS AND ZYRTEC HIVES RELIE
12/27/2007

7 CETIRIZINE HYDROCHLORIDE TABLETS, (OTC) 5 MG AND 10 MG
SANDOZ INC.
ZYRTEC ALLERGY TABLETS AND ZYRTEC HIVES RELIE
12/27/2007

8 DICLOFENAC SODIUM OPHTHALMIC SOLUTION, 0.1%
BAUSCH & LOMB INC.
VOLTAREN OPHTHALMIC SOLUTION
12/28/2007

9 BALSALAZIDE DISODIUM CAPSULES 750 MG
ROXANE LABORATORIES, INC.
COLAZAL CAPSULES
12/28/2007

10 DICLOFENAC SODIUM OPHTHALMIC SOLUTION, 0.1%
NEXUS PHARMACEUTICALS, INC.
VOLTAREN OPHTHALMIC SOLUTION
12/28/2007

11 GRANISETRON HYDROCHLORIDE INJECTION, 0.1 MG (BASE)/1 ML; PACKAGED IN 0.1 MG (BASE)/ 1 ML SINGLE-USE VIALS
APP PHARMACEUTICALS, LLC
KYTRIL INJECTION
12/31/2007

12 GRANISETRON HYDROCHLORIDE TABLETS, 1 MG (BASE)
BARR LABORATORIES, INC.
KYTRIL TABLETS
12/31/2007

13 GRANISETRON HYDROCHLORIDE INJECTION, 1 MG (BASE)/ML; PACKAGED IN 4 MG (BASE)/4 ML MULTIPLE-DOSE VIALS
BAXTER HEALTHCARE CORPORATION
KYTRIL INJECTION
12/31/2007

14 GRANISETRON HYDROCHLORIDE TABLETS, 1 MG (BASE)
TEVA PHARMACEUTICALS USA
KYTRIL TABLETS
12/31/2007

15 GRANISETRON HYDROCHLORIDE TABLETS, 1 MG (BASE)
COREPHARMA LLC
KYTRIL TABLETS
12/31/2007

16 GRANISETRON HYDROCHLORIDE TABLETS, 1 MG (BASE)
ROXANE LABORATORIES, INC.
KYTRIL TABLETS
12/31/2007

17 GRANISETRON HYDROCHLORIDE INJECTION, 0.1 MG (BASE)/ML; PACKAGED IN 0.1MG (BASE)/1 ML SINGLE-USE VIALS
WATSON LABORATORIES, INC.
KYTRIL INJECTION
12/31/2007

18 GRANISETRON HYDROCHLORIDE INJECTION, (PRESERVATIVE-FREE) 1 MG (BASE)/ML; PACKAGED IN 1 MG (BASE)/1 ML SINGLE-DOSE VIALS
TEVA PARENTERAL MEDICINES, INC.
KYTRIL INJECTION
12/31/2007

Eisai Mistake Allows Dismissal in Donepezil ODT Case

On December 20, 2007, the District Court in New Jersey granted Mutual’s Motion to Dismiss. Apparently, when Mutual filed its ANDA, there were no patents listed in the Orange Book. When Eisai submitted patents for Orange Book listing for the ODT product, it mistakenly filled out the forms (3542a instead of 3542) with the NDA number and product name of the tablet formulation, so FDA did not list any patents for ODT. As such, Mutual had no patents to certify against, and Eisai sued Mutual anyway for infringement of the sole Orange Book patent US4895841 (which covers Donepezil as product and also covers method of use in senile dementia of the Alzheimer type). In its press release, Eisai implies that they have reached an agreement (perhaps in lieu of an appeal of this decision as reported earlier in this blog) that Mutual will give Eisai 45 days notice before it launches. While the patent expires in 2010, there is a likelihood that Mutual will be approved before then, and if it decides to launch, expect to see a preliminary injunction filed by Eisai.

Tysabri (natalizumab) approved for Crohn's disease

Tysabri, a controversial drug used to treat multiple sclerosis, may also be used for patients with a moderate to severe form of another autoimmune illness, Crohn's disease, the USFDA announced Monday.
But the drug also comes with a rare but serious risk of a potentially deadly brain infection, as well as other side effects, so it must be used carefully, the FDA said in a press teleconference.
Crohn's is a serious, often painful, inflammatory bowel disorder that affects about 600,000 people in the United States. It can involve intestinal bleeding, diarrhea, weight loss, arthritis, skin problems, fever and anemia.
Tysabri (natalizumab), a monoclonal antibody used to treat MS, has been under a cloud of controversy for some time. The drug works by attaching itself to white blood cells called lymphocytes and preventing them from entering the brain, where they do damage that causes the disabling symptoms of MS.
But the drug has a checkered past. It first received USFDA approval in November 2004, only to be pulled from the market three months later after several patients in clinical trials developed a rare but deadly viral infection of the brain called progressive multifocal leukoencephalopathy (PML).
In June 2006, the FDA allowed the drug to return to the market but with strict conditions. According to the new guidelines, Tysabri can only be administered by approved doctors, at infusion sites and pharmacies that register and comply with a patient-safety program called CD Touch, designed by Biogen Idec, the maker of Tysabri, and approved by the USFDA.

New Para IV filings

Epzicom®(abacavir and lamivudine) Tablets 600/300mg on 9/27/2007

Namenda®(memantine) Tablets 5 ,10, 15 and 20mg on 10/16/2007

Zegerid®(omeprazole and sodium bicarbonate) Powder for Oral Suspension on 8/24/2007

Zantac 150®(ranitidine) Tablets 150mg on 10/30/2007

Exforge®(amlodipine and valsartan) Tablets 10/160mg on 10/1/2007

Opana ER®(oxymorphone) Extended Release Tablets 5, 10, 20 and 40mg on 11/23/2007

U.S Supreme court reject appeal on experimental drugs access

The U.S. Supreme Court turned away an appeal that sought to give terminally ill people greater access to experimental drugs that may save their lives.
The justices, without comment, rebuffed a patient-advocacy group that said the USFDA is placing unconstitutional obstacles in the way of people who have exhausted their approved treatment options.
``Huge numbers of Americans die each year after being denied access to developmental drugs that might have prolonged their lives -- drugs that, in many instances, later received FDA marketing approval,'' argued the group, the Abigail Alliance for Better Access to Developmental Drugs.
The Bush administration and the FDA urged the court not to hear the case, saying the appeal sought to ``revive a brand of judicial intervention that this court foreswore long ago.''
The case involved people who aren't included in the clinical trials conducted by pharmaceutical companies or the expanded access programs that drugmakers offer for some experimental treatments.
Under federal law, people who aren't in those groups and want access to experimental treatments must persuade the FDA that the benefits outweigh the risks, a process that requires what Abigail Alliance calls a ``mountain of regulatory paperwork.''

Taro and Breckenridge Strike Deal with Novartis On Oxcarbazepine Patent

Two generics manufacturers have settled patent litigation over their abbreviated new drug applications for oxcarbazepine, the active ingredient in Swiss giant Novartis AG's popular anti-epileptic Trileptal, permitting both to sell tablets in the U.S. immediately
Taro Pharma (reported earlier in this blog) and Breckenridge have settled their lawsuit with innovator Novartis
Breckenridge Pharmaceutical, Inc. announced today that it settled "Paragraph IV" litigation with Novartis concerning Trileptal(R) and that the USFDA approved Breckenridge's Abbreviated New Drug Application for oxcarbazepine 150mg, 300mg and 600 mg tablets in the United States ("Oxcarbazepine Tablets").
Breckenridge enjoys a shared 180-day exclusivity period with Taro and will immediately launch Oxcarbazepine Tablets 150 mg, 300 mg, and 600 mg. Oxcarbazepine Tablets are AB rated to Trileptal(R), a $600 million brand name drug marketed by Novartis Pharmaceuticals Corporation, and are used in treating seizures.

Caraco got final approval for Glipizide/Metformin Hydrochloride Tablets

Caraco Pharma, announced today that the USFDA has granted final approval for the Company's Abbreviated New Drug Application (ANDA) for Glipizide/Metformin Hydrochloride Tablets, 2.5/250 mg, 2.5/500 mg and 5/500 mg (Glipizide/Metformin HCl).Glipizide/Metformin HCl is indicated as initial therapy, as an adjunct to diet and exercise, to improve glycemic control in patients with type 2 diabetes whose hyperglycemia cannot be satisfactorily managed with diet and exercise alone. It is also indicated as second-line therapy when diet, exercise, and initial treatment with a sulfonylurea or metformin do not result in adequate glycemic control in patients with type 2 diabetes. Our generic Glipizide/Metformin HCl is the bioequivalent to Metaglip(R), a registered trademark of Bristol-Myers Squibb Company. According to IMS Data, for the twelve months ended September 2007, Glipizide/Metformin HCl generic and brand products (Metaglip(R)) combined had annual sales of approximately $25 million.Daniel H. Movens, Caraco's Chief Executive Officer, said, "We are pleased to gain this approval from the FDA. Our focus continues to be working towards expanding our product line effectively, including products that are already available generically in the market that potentially can add measurable value."

Teva got tentative approval for Donepezil tablets

Teva Pharmaceutical Industries Ltd. (in a press release) announced today that the USFDA has granted tentative approval for the Company's Abbreviated New Drug Application (ANDA) to market its generic version of Eisai's Alzheimer's treatment Aricept(R) (Donepezil Hydrochloride) Tablets, 5 mg and 10 mg. The brand product had annual sales of approximately $1.6 billion in the United States for the twelve months ended September 30, 2007, based on IMS sales data.Teva is currently in patent litigation concerning this product in the U.S. District Court for the District of New Jersey involving Teva's paragraph IV certification to U.S. Patent No. 4,895,841. Although a trial date has not been set, the Court has set a briefing schedule for a preliminary injunction motion under which Eisai must file its request no later than February 15, 2008. Final approval of this ANDA is anticipated on or about April 26, 2008, upon expiry of the mandatory stay of approval associated with the patent litigation.

U.S. Lipitor patent (US4681893) initially rejected

U.S. patent officials have initially rejected claims for the basic patent US4681893 on Pfizer Inc's blockbuster Lipitor cholesterol treatment, although the drug maker said on Monday it remained confident the patent would ultimately be upheld.
The patent, which expires in March 2010, will remain valid and enforceable while U.S. officials re-examine it, a process that could take as long as a few years, Pfizer said, allowing the company to maintain its grip on the product and ward off generic rivals over that time.
"Given the process can take an extended period of time, it probably will go past March 2010, so we're not as concerned," Edward Jones analyst Linda Bannister said.
A law firm that has represented generic drug maker Ranbaxy Laboratories Ltd in July requested a re-examination of the basic patent of Lipitor, the world's biggest-selling drug with sales of about $12 billion. Any shortening of Pfizer's exclusive hold on Lipitor would be a blow to the company.
An initial rejection is not unusual, and Pfizer will follow with a response in the next two months, the company said.
"We continue to believe that the basic patent was properly granted and will be upheld on re-examination," General Counsel Allen Waxman said in a statement.
Pfizer also wants U.S. officials to reissue a second Lipitor patent, which could extend its hold on the drug until June 2011.

Forest Laboratories File Lawsuits Against Several Companies for Patent Infringement Of Memantine

Forest Laboratories, Inc. , Forest Laboratories Holdings, Ltd., Merz Pharma GmbH & Co. KgaA, and Merz Pharmaceuticals GmbH announced that they have filed lawsuits in the U.S. District Court for the District of Delaware against several companies for infringement of US5061703 (the '703 patent), which relates to Forest's Namenda (Memantine hydrochloride) product and covers A method for the prevention or treatment of cerebral ischemia comprising the step of administering, to a patient in need thereof, an effective amount of Memantine. The defendants named in the lawsuits include Barr Laboratories, Inc., Cobalt Laboratories, Inc., Lupin Ltd., Orchid Chemicals & Pharmaceuticals Ltd., Teva Pharmaceuticals USA, Inc., Upsher-Smith Laboratories Inc., Wockhardt Ltd., and related companies and subsidiaries thereof. The '703 patent expires in April 2010. Forest has applied for patent term extension which, if granted, would extend the '703 patent until September 2013.
As previously reported, Forest had received notification from several companies that they had filed Abbreviated New Drug Applications with Paragraph IV certifications to obtain approval to market generic versions of Namenda.

Namenda (memantine hydrochloride) is indicated for the treatment of moderate to severe dementia of the Alzheimer's type. The product had sales of approximately $824 million in the U.S., based on IMS sales data ending October 2007.

Merck signed an authorized-generic deal on Alendronate

Merck has signed an authorized-generic deal with an unidentified company to market a generic version of its blockbuster osteoporosis drug Fosamax (Alendronate sodium trihydrate), which could go on sale next month.
Merck spokesman Ron Rogers declined to identify the generics company on Friday, saying details of the deal were proprietary at this time.
Fosamax's key U.S. patent is set to expire on Feb. 6, which will clear the way for generic competition.
Teva and Barr are planning to launch generic copies of Fosamax. Under federal law, Teva and Barr have been scheduled to be the only third-party marketers of generic Fosamax for about six months, because they were the first to file for Food and Drug Administration approval of generic Fosamax.
But the six-month exclusivity period doesn't stop Merck from selling its own generic, either by itself or with a generic-company partner. In recent years, Merck and other branded pharmaceutical companies have begun to strike these authorized-generic deals.
Critics say authorized-generic deals undercut the competitive advantage held by the generic companies that are supposed to have six-month exclusivity periods. Branded manufacturers, however, say the deals give consumers another generic option.
The Federal Trade Commission is now conducting a study of the competitive impact of authorized-generic deals. It recently requested information from numerous pharmaceutical companies about the deals.
Fosamax is one of Merck's best-selling drugs and was forecast to generate sales of $2.9 billion to $3.1 billion in 2007. However, sales are expected to plunge to $1.1 billion to $1.4 billion this year as a result of generic competition. Earlier this week, the FDA also advised doctors and patients about the possibility of severe and sometimes incapacitating bone, joint or muscle pain linked to Fosamax and other osteoporosis drugs.
Barr said Friday that it plans to launch a generic version of Fosamax 70 milligram tablets on Feb. 6 and that it is entitled to the 180-day exclusivity period.
"We had anticipated sharing the exclusivity with Teva for this product," the company said. "We are not surprised that Merck is launching an authorized generic, as this has become a common antigeneric strategy for brand companies."
A Teva spokeswoman couldn't immediately be reached for comment.

Crucial win for Pfizer on Celecoxib

Pfizer Inc announced today that a New York state court ruled in favor of the company on an important motion relating to litigation over Pfizer's Celebrex (Celecoxib) medication. New York Supreme Court Justice Shirley W. Kornreich ruled that the plaintiffs suing Pfizer in New York failed to present reliable scientific evidence necessary to prove that Celebrex can cause heart attacks and strokes at 200 mg daily - the most commonly prescribed dosage of the Pfizer pain medication. In her decision, Justice Kornreich held that "...with regard to Celebrex at 200mg/d[aily], the scientific evidence, whether for a heart attack or stroke, is just not there."
The ruling follows a similar decision in November 2007 by the U.S. District Court of Northern California in the Celebrex multi-district federal litigation. In the federal court decision, the Court held there are "no randomized controlled trials or meta-analyses of such trials or meta-analyses of observational studies that find an association between Celebrex 200 mg/day and a risk of heart attack or stroke."
Together, the two decisions render certain expert opinions inadmissible, which we believe could result in the dismissal of many Celebrex cases. The majority of the Celebrex cases are pending in the two courts that issued the decisions.
Most of the Celebrex lawsuits were filed after the USFDA held advisory committee hearings in 2005 on the cardiovascular risk of non-steroidal anti-inflammatory drugs (NSAIDS), including Celebrex. The FDA concluded that based on the available data, Celebrex's benefits outweigh its risks for appropriate patients at approved doses. As a result, Celebrex has remained continuously on the market since it first became available to patients in 1999. Although neither the New York nor federal district court ruling excludes – at this stage - all expert testimony concerning risk of heart attack or stroke in connection with plaintiffs who took more than 200 mg/daily of Celebrex in the ongoing litigation, Pfizer intends to challenge the admissibility of evidence that such higher doses might cause heart attacks or strokes in those specific cases.
"We are pleased with Justice Kornreich's decision which, like the federal court decision, recognizes the lack of any credible evidence linking Celebrex, at its most common dosage form, with heart attacks or strokes," said Pfizer General Counsel Allen Waxman. "We believe that these rulings will greatly limit the scope of this litigation, and we intend to continue to vigorously defend the cases against us."

Etanercept Shows Promise in Reversing Symptoms of Alzheimer's

A patient with Alzheimer's disease had their condition improve hugely just minutes after receiving a special injection of a prescription drug approved to treat psoriasis and rheumatoid arthritis and other conditions, according to a new study.
The drug, co-marketed in the U.S. by Amgen and Wyeth under the name Etanercept (Enbrel), dramatically reversed symptoms of an Alzheimer’s disease sufferer minutes after it was injected into the patient's spine, researchers in the U.S. discovered. The drug, sold in Australia as Etanercept, has also been used off-label for treating Alzheimer's.
Etanercept is a recombinant human soluble tumor necrosis factor-alpha (TNFα) receptor fusion protein. It is a large molecule, with a molecular weight of 150 kDa., that binds to TNFα and decreases its role in disorders involving excess inflammation in humans and other animals, including autoimmune diseases such as ankylosing spondylitis, juvenile rheumatoid arthritis, psoriasis, psoriatic arthritis, rheumatoid arthritis, and, potentially, in a variety of other disorders mediated by excess TNFα.
A report on the new study appeared in the Journal of Neuroinflammation this week.

FDA delays review of Methylnaltrexone NDA

Wyeth and Progenics Pharmaceuticals Inc (In a press release) said on Thursday that USFDA have delayed a review of their experimental drug to treat opioid-induced constipation in order to further review certain safety data.
The companies said the USFDA has asked for the results of a recently completed study of the drug, methylnaltrexone, on QT prolongation, a disorder of the heart's electrical system that can lead to a life-threatening form of ventricular tachycardia in which the heart is unable to pump blood throughout the body.
The companies said the study submitted to the FDA examined the effect of intravenous methylnaltrexone, which is being developed for post-operative ileus, a dysfunction of the gastrointestinal tract following surgery.
The companies said there was no evidence of an effect of the drug on QT prolongation. They said the FDA now hopes to act on the drug around April 30, three months later than previously.
The companies are seeking to market a subcutaneous version of the drug for constipation associated with the use of opioid painkillers.

Roche sign technology transfer pact in Africa and Asia

Roche announced that it has entered into four new technology transfers with local manufacturing companies in Africa and Asia; Regal Pharmaceuticals in Kenya, CAPS Holdings in Zimbabwe, Shelys Pharmaceuticals in Tanzania and Beximco Pharmaceuticals Ltd in Bangladesh. As part of Roche's Technology Transfer Initiative, these companies will be provided free of charge with the technical expertise to manufacture generic HIV medicine, based upon the processes to produce saquinavir, Roche's 2nd linel HIV medicine.
Since its launch two years ago, Roche has signed Technology Transfer agreements with a total of nine companies across sub-Saharan Africa and the world's Least Developed Countries. Furthermore Roche has received expressions of interest from a total of 35 manufacturers in 15 eligible countries, including Kenya, Ghana, Zimbabwe and Nigeria. Roche will continue to work with these individual applicants to assess production capabilities.
In addition to these four new agreements, Roche has expanded the Technology Transfer Initiative with training seminars for local manufacturers across sub-Saharan Africa and the world's Least Developed Countries. These sessions focus on the development of improved manufacturing processes and provide a forum for Roche to share its knowledge and experience with those who have access to fewer resources. The knowledge gained by local manufacturers enables them to strengthen their manufacturing capability, increase manufacturing knowledge on the production of medicines beyond HIV.
Rahul Malhotra, CEO Shelys Pharmaceuticals, Tanzania commented: "The practical support that Roche has provided has been a great learning experience for my team, enabling us to make improvements to our entire technical and quality systems. We have been enthused by this partnership and are eager to work with Roche on this initiative to help meet the needs of our people suffering from HIV infections, and improve availability of these badly needed medications."
Roche's dedicated team will work onsite at manufacturing facilities at all four locations and from its headquarters in Switzerland to undertake the technology transfers. The companies will be able to produce saquinavir for supply throughout countries in sub-Saharan Africa, and to those defined as Least Developed by the United Nations, due to Roche's policy of not filing patents on antiretroviral medicines in these countries.

Teva Drops Patent Suit Against Taro Over generic Carvedilol

Teva Pharmaceutical Industries Ltd. has dropped a patent infringement lawsuit against Taro Pharma over congestive heart drug failure treatment carvedilol. Teva filed a notice on Monday in the U.S. District Court for the Southern District of New York to dismiss the suit against Taro and its U.S. affiliate without prejudice. The suit was filed in June 2007, but Taro was never formally served. The deadline to serve the complaint was continually pushed back while the drug companies engaged in settlement negotiations. Terms of the deal were not disclosed. Taro currently has no plans to launch the product, said Roanne Kulakoff, a spokeswoman for Taro. At this time, there are a number of other players in the market so Taro has no plans to launch at this time.
A spokeswoman for Teva said the company had no comment. Taro was one of more than a dozen pharmaceutical companies targeted by Teva in suits over their plans to market generic versions of GlaxoSmithKline's drug Coreg. The lawsuits concern US6699997, US6710184, US7056942 and US7126008 all of which are owned by Teva. The patents cover carvedilol, the active ingredient in Coreg.
Carvedilol is a non-selective beta blocker indicated in the treatment of mild to moderate Congestive Heart failure(CHF). It is marketed under various Trade names like Coreg (GSK), Dilatrend (Roche) and Eucardic (Roche). Carvedilol is the only bata blocker which is(which reduce cardiomyopathy of heart muscle) used in CHF therapy.
After Glaxo's patent covering Coreg expired on March 5, the company was granted six months of pediatric exclusivity (PED). But Teva said in its lawsuits that the generic companies' plans to manufacture and sell Coreg's API to third parties constituted an imminent threat of infringement. In September, the USFDA approved 14 Abbreviated New Drug Applications for carvedilol including those from Taro, Actavis Elizabeth and Dr. Reddy's Laboratories after Glaxo's exclusivity period ended. Taro's ANDA sought to market generic versions of Coreg in four different dosages. Total sales of the drug (Coreg and Coreg CR) exceeded $1 billion in 2006-2007.

Barr to fight against Oxaliplatin product patent

Barr Laboratories Ltd. has initiated a challenge of the patents listed by Sanofi-Aventis U.S. LLC in connection with its Eloxatin(R) (Oxaliplatin Aqueous Solution), 5mg/mL Injectable.Barr filed an ANDA containing a paragraph IV certification against US5338874 {(Expiry: 10-7-2013) which covers Optically pure cis-oxalato (trans- 1-1,2-cyclohexanediamine) Pt(II) as product} for a generic Eloxatin product with the USFDA, and following FDA notification of the application's acceptance for filing, the Company notified the New Drug Application (NDA) and patent owner. There are 6 orange book listed patent and innovator sued Barr over US5338874.On January 4, 2008, Sanofi-Aventis U.S. LLC, Sanofi-Aventis and Debiopharm S.A. filed suit in the U.S. District Court of New Jersey on 4th january 2008 to prevent the Company from proceeding with the commercialization of its product. This action formally initiates the patent challenge process under the Hatch-Waxman Act.

Indian pharma news

Stride to shut down sick manufacturing unit
Strides Arcolab a leading global manufacturers of pharmaceuticals, has announced that its loss making manufacturing operation for OTC and nutraceuticals for soft gelatine products in the U.S.A market has been shut down.The changing regulatory framework in the U.S.A for OTC and nutraceutical products does not make the plant viable anymore. The facility incurred an operating loss of approx. Rs 280 mio (US $7.10 mio) in the financial year 2007.The company continues to engage with interested parties on the disposal of the asset but the ceasing of the manufacturing operations will ensure the immediate reduction of losses in its operations in the USA.The soft gelatin business continues to be attractive for Strides and its Indian Plant is fully geared to meet enhanced demand that will be relocated to India.

Wockhardt to launch sertraline tablets in USA

Wockhardt Ltd has announced that the company will be launching sertraline tablets in the United States. The company has received approval from the United States Food & Drug Administration (US FDA) for marketing the tablets containing 25mg, 50mg and 100mg sertraline hydrochloride, which is used for treating depression. Sertraline is the generic name for the brand Zoloft, sold in the US by Pfizer.
Wockhardt's Sertraline tablets will be launched in the US market within the next few weeks. According to IMS, the total market for Sertraline tablets in the US is $1.1 billion equivalent to over 1.4 billion tablets. Wockhardt has several products including injectables in the CNS segment.In the prescription generic pharmaceutical market, the company has been consistently growing market shares for all its products. Wockhardt markets over fifty products in the US.The Sertraline tablets are manufactured at the US FDA certified formulation plant at Waluj, Maharashtra. The product was developed in-house. Wockhardt is one of the few companies with end-to-end integrated capabilities for its products, starting with manufacture of the oral and sterile API's, the dose forms and marketing through the wholly-owned subsidiary in the US, enabling the company to capture maximum value.

Controller of patent dismissed opposition against Bilcare patent

The Controller of Patents pronounced its decision of dismissing the two oppositions against Bilcare's (patent no 197823) on Metallized Packaging Films and uphold the validity of the said patent. The judgment was pronounced after multiple hearings from Mumbai Patent office and the Assistant Controller of Patents stated :"In view of my findings as above after careful consideration of statements, evidences and arguments at the hearing, the opposition is dismissed and the opponent shall pay to the applicant (the Patentee) the costs as annexed herein." "The costs to be paid to the Patentee by the opponents (Rs. 30, 000 in one case and Rs. 29,500 in another) included costs for irrelevant citations and documents".Bilcare had filed its patent application for its invention of metallized packaging films on March 03, 2004. The Controller of Patents granted the Patent No 197823 by sealing the patent on 29th December 2005. The invention related to a multi layer thermoformable, translucent PVC film with metallization to provide distinctive features for identity as well as effective anti-counterfeit solution. This novel film became an immensely valuable packaging material for the packaging of pharmaceutical products. The Indian pharmaceutical industry realized and appreciated the novelty and began using this film for packaging their products. Shelcal (a Calcium supplement manufactured by Elder Pharmaceuticals) became the first product in the world to use this novel packaging material. The metallized film created a distinctive identity for several widely used medicines.

Taro settle lawsuit with Novartis on Oxcarbazepine tablets

Taro Pharmaceutical Industries Ltd. has settled a pending lawsuit with Novartis and will be launching Oxcarbazepine tablets 150 mg, 300 mg, and 600 mg in the United States.
Oxcarbazepine tablets, marketed by Novartis as Trileptal tablets, is a prescription pharmaceutical product used in treating seizures. Taro recently settled litigation with Novartis regarding Taro's "Paragraph IV" certification challenging Novartis' patent protection on Trileptal. On November 15, 2007, Taro received approval from the U.S. Food and Drug Administration for its Abbreviated New Drug Application for Oxcarbazepine Tablets 150 mg, 300 mg, and 600 mg. The litigated patent is US7037525 (Expiry 12-8-2018 with PED), which covers a method of treating seizures, which comprises administering a formulation of oxacarbazepine having improved bioavailability, wherein said oxacarbazepine consists essentially of oxacarbazepine having a maximum residue on a 40 .mu.m sieve of less than or equal to 5%.
The company did not immediately launch the product at that time, pending settlement of the litigation with Novartis. Taro plans to launch Oxcarbazepine tablets in the near future. According to industry sources, Trileptal tablets currently have annual U.S. sales of approximately $700 million.

USFDA approves new formulation of tadalafil

Eli Lilly announced (In a press release) today that the USFDA has approved Cialis(R) (tadalafil)(1) for once daily use (2.5 mg and 5 mg), an oral medication taken once per day to treat erectile dysfunction (ED). When Cialis for once daily use is taken daily, men can attempt sexual activity at anytime between doses.Currently available in parts of Europe, this low-dose daily treatment option of Cialis may be most appropriate for men with ED who anticipate more frequent sexual activity (e.g. twice weekly). For other men, Cialis taken as needed - the previously approved dosing regimen - may be most appropriate.In clinical trials, when taken without restrictions on the timing of sexual activity, Cialis for once daily use improved erectile function over the course of therapy."ED can be a chronic condition like diabetes or high blood pressure," said Ridwan Shabsigh, M.D., Director of the Division of Urology at Maimonides Medical Center in New York. "As a urologist, I know couples like to have choices and will appreciate the availability of Cialis for once daily use."Cialis for use as needed transformed the U.S. ED market when it was approved in 2003 as the first and only PDE5 inhibitor clinically proven to provide sustained efficacy for up to 36 hours. Cialis for once daily use provides a new option for men who may be looking for a dosing option that can be taken without regard to timing of sexual activity. In consultation with their physician, patients now have the freedom to choose the dosing regimen that is appropriate for them."We strive to provide patients with solutions that fit their needs and Cialis for once daily use delivers on this promise," said Shawn Heffern, Cialis U.S. Director of Brand Marketing at Lilly. "Now, patients have two options - some may prefer the up to 36 hours of efficacy provided by Cialis for use as needed while others may want the unique benefit provided by this daily dosing option."Additionally, Lilly's wholesale pricing for Cialis for once daily use will be comparable to Cialis for use as needed such that patients who currently use two or more pills per week of Cialis for use as needed should not experience higher treatment costs with Cialis for once daily use.The FDA's approval of Cialis for once daily use was based upon the evaluation of the comprehensive data package for the daily dosing option. The data include results from three phase III randomized, double-blind, placebo- controlled studies. Men with ED who participated in these clinical studies and who took tadalafil 2.5 mg and 5 mg once daily without regard to their timing of sexual activity experienced improved erectile function compared with those taking placebo.(2) Cialis 5 mg, 10 mg and 20 mg have been approved in the United States for as-needed treatment of ED since November 2003.The most commonly reported adverse events were headache, indigestion, back pain, muscle aches, nasal congestion, flushing and pain in limb. Most adverse events reported with tadalafil were transient and generally mild or moderate.

regulatory approvals to Clinical Pharmacology unit of GVK Bioscience

The Clinical Pharmacology Unit of GVK Biosciences has received approvals from regulatory bodies such as US FDA, AFSAAPS, WHO and ANVISA. The approvals open up global markets to GVK BIO's clients in the US, Europe and Latin American countries in addition to the domestic sector.Manni Kantipudi, president of GVK Bio stated, "The approvals validate GVK BIO's high quality systems and practices".As a first step, GVK Bio has expanded and built a new state-of-the-art Bioanalytical facility in addition to the existing one to cater to the growing business demands. GVK Bio is also setting up its own Clinical Laboratory and aims for an early accreditation."GVK BIO aims to be a full service Clinical Research Organization offering services from BA/BE to phase I through phase IV Clinical Trials", said Mr. G V Sanjay Reddy, managing director, GVK Bio.

Indian Insulin patent for Novo Nordisk

Denmark based biotech company Novo Nordisk has lately received an Indian Patent No. 209529 (the ‘529 patent) for chemically stable aqueous insulin preparation using comparatively low halogenide (sodium chloride) concentrations (see Official Gazette Journal No. 50/2007 dated December 14, 2007). The patent is issued by the Chennai Patent Office against the mail-box Application No. 1337/MAS/1997 claiming priority from Danish Application No. 685/96 dated June 20, 1996. Interestingly, the ‘529 patent is Indian equivalent of the US Patent No. 5,866,538 which is currently been listed with the USFDA Orange Book for three approved Insulin Injection products -- namely Novolog (insulin aspart recombinant), Levemir (Insulin determir recombinant), and Novolog Mix 70/30 (insulin aspart protamine recombinant). Considering that stability forms a major technical issue in long-term insulin storage, the ‘529 patent seems to give Novo an edge over the generic competitors in ever-expanding domestic insulin market

Purdue Pharm blocked generic Oxycontin

Purdue Pharma can enforce its patent on the painkiller OxyContin to block generic competition from companies including KV Pharmaceutical Co., a U.S. judge has ruled.U.S. District Judge Sidney Stein in New York rejected claims by KV, Covidien Ltd.'s Mallinckrodt and Novator's Actavis Totowa that the patent was unenforceable because Purdue withheld key information from the U.S. Patent and Trademark Office.There is "scant evidence that Purdue intended to deceive the [patent office,]" Stein said in an opinion issued Monday. The company's errors in providing the information were either of "low materiality" or "made in good faith," the judge said."We always have maintained that our patents relating to OxyContin were properly issued and are therefore enforceable," said Tim Bannon, a spokesman for Stamford-based Purdue. "We are gratified that the court has agreed with us."Still pending are issues of whether the patent is valid and infringed. In 2005, Stein ruled it wasn't, and generic-drug companies including Endo Pharmaceuticals Holdings Inc. began selling copycat versions. A U.S. appeals court sent the case back for review in 2006."We are disappointed in the district court's ruling, but this is not the end of the lawsuit," Covidien spokesman Eric Kraus said. "This is ongoing litigation."Covidien, based in Hamilton, Bermuda, is the medical supplies maker spun off from Tyco International Ltd.

King Pharmaceutical Settle lawsuit with Core on metaxalone

King Pharma had ended a patent infringement lawsuit filed against CorePharma related to its drug Skelaxin (metaxalone). SKELAXIN® is a muscle relaxant with a low chance of drowsiness or side effectsAll the claims, including Core's counterclaims, were dismissed without prejudice in a New York federal court.After the dismissal was announced in a filing with the Securities and Exchange Commission. Under the terms of a termination agreement King entered with Core on Jan. 2, King will grant Core a nonexclusive license to make and sell a 400 mg metaxalone product, in what amounts to a generic form of Skelaxin.The license will be effective on Jan. 1, 2012, or six months after a third party sells a generic form of Skelaxin, whichever occurs first.The lawsuit was first filed on March 7, 2003. Other suits were filed against Eon Labs Inc. and Mutual Pharmaceutical Co., both of whom King said had filed to make a generic form of Skelaxin.

Genzyme in deal with Isis for cholesterol lowering drug

Genzyme will pay as much as $1.9 billion to develop and sell a cholesterol drug from tiny Isis Pharma. Isis will pocket at least a third of the profits from the product if it is approved.
Unlike other cholesterol medicines, Isis' experimental mipomersen will be targeted at patients whose high cholesterol is caused by a relatively rare genetic disease. Isis will get $325 million upfront in the form of a $175 million fee and a $150 million investment that values Isis shares at more than double their current value. Depending on how the drug does with the USFDA and other regulators, Isis could get $825 million more in milestone payments. Another $750 million in milestones will be based on the commercial success of mipomersen. Shares of Isis rose more than 50% in after-hours trading Monday.
The two companies will split the profits of the medicine. At first, Isis will get 30% of these profits, but as worldwide sales increase, so will Isis' take. If and when mipomersen hits annual sales of $2 billion, profits will be split 50-50.
Mipomersen is a drug that blocks the function of a gene that allows cholesterol to circulate in the blood. It shows promise for all forms of high cholesterol, but the prospects are best in a rare disease called familial hypercholesterolemia (FH). The worst form, caused by having two bad copies of a particular cholesterol gene, afflicts only a few hundred people. Their cholesterol levels can soar to six times the normal level and cause heart attacks in patients who are in their 20s.
Some 600,000 Americans have the more common form of FH, which is caused by a single bad copy of the cholesterol gene and causes levels of cholesterol that are just above the upper limit of normal.

Court upholds stent patent infringement

The Court of Appeals for the Federal Circuit in Washington, D.C. today upheld two separate 2005 jury verdicts that found Medtronic, Inc. and Boston Scientific Corporation infringed coronary stent patents owned by the Cordis Corporation, a Johnson & Johnson company. Cordis now intends to ask the U.S. District Court in Delaware to reinstate the damages judgments of $271 million against Medtronic and $324 million against Boston Scientific, plus interest."We are very pleased that the Court of Appeals has recognized the validity of the prior verdicts," said Todd Pope, Worldwide President, Cordis Corporation. "We will urge the U.S. District Court to move expeditiously to reinstate the two previous damages judgments, along with the interest that has accrued during the appeals process."Injunctive relief is not an issue because the infringing Medtronic and Boston Scientific stents are no longer on the market. In March of 2005, separate juries found that Medtronic's GFX and Microstent II infringed Cordis' Palmaz (762) and Schatz (984) patents, and that Boston Scientific's NIR stent infringed the Palmaz patent. The Palmaz and Schatz patents relate to the fundamental design of the first coronary stent developed and introduced by Cordis.Both patent infringement cases were originally tried in 2000, with Cordis receiving favorable jury verdicts. After a series of procedural rulings and appeals, both cases were retried in March of 2005, with Cordis prevailing again.

Generic attack

A recent report has detailed the challenges facing the pharma industry as the generic flood gates open, with the constant advice to start planning early still apparently not heeded by a bewildering number of firms.Generics manufacturers are coming of age as branded drugs worth billions of dollars come off patent and open the way for cheaper versions to cash in on established patient populations.According to IMS Health, sales by generic manufacturers in 2006 amounted to $54.1bn, over 2.5 times the value just eight years earlier. By 2011, drugs worth over $60bn are expected to come off patent, with existing generics already commanding 60 per cent of US prescriptions.The branded pharmaceutical industry is feeling the heat, with firms well aware that the cushion of patent protection will not last forever and when the generic wave breaks, revenues will be hit hard.2007 saw numerous firms forced to 'restructure' as a result of generic challenges and a difficult environment in the sector, and according to a recent report by Cutting Edge Information, many pharma firms still fail to think far enough in advance to mitigate the impact of generic competition on their revenue streams."Companies regularly wait too long…to prepare for generic competition," say the report authors."Now, with generics manufacturers exhibiting legal aggression and a willingness to file [abbreviated new drug applications] years before patent expiration, it is imperative to start planning early for the loss of market exclusivity."66 per cent of companies surveyed for the report tended not to even begin generics planning until at least two years after product launch, with a paltry 34 per cent thinking ahead and planning for generic competition at the launch of a branded drug or earlier. "A majority of survey respondents scramble to think about generics in the final four years before patent expiration," the authors state."Because options that rely on scientific and clinical development often take years to execute, companies with a lifecycle management strategy that incorporates counter-generics planning at least four to six years before patent expiration afford themselves the most options in retaining revenue."While this advice might seem obvious, the number of companies forced to make cutbacks in spending and staffing this year as a result of generic competition and "current market conditions" reads like a Who's Who of the industry, with numerous branded firms suffering as generics manufacturers plunder the rich revenue streams with their cheaper products as patents expire.There are of course options for those companies with patent expirations looming on the horizon, but again, forward planning is the buzz phrase for pharmas hoping to avoid brutalisation of their sales.The most popular option, despite the extended time required for R&D, is to develop new formulations of existing drugs, with different dosages or extended release profiles. 58 per cent of the report's survey respondents indicated that their company had launched a new formulation of an existing product.Line extension tactics such as this can help switch patients from older, threatened brands to newer products with extended market exclusivity, but come with the added risk and expense of clinical, regulatory and commercial hurdles.The report authors suggest that another way of helping to prepare for generic competition is by involving multiple stakeholders in counter-generic planning activities:"More groups involved in a brand's fortunes means that more parties are interested in the brand's total lifecycle," the report suggests."A diverse group of stakeholders helps to ensure that counter-generics planning occurs at an early point in brand life. Clinical development groups will consider next-generation options, for example, while market research models the impact of patent expirations for the brand and its competitors."Sound counter-generics planning is likely, however, to combine a number of different strategies ranging from short-term responses to imminent challenges to more long-term lifecycle management tools, as well as acknowledging the potential of authorised generics, generics subsidiaries or over-the-counter (OTC) possibilities."A multi-tiered counter-generics plan positions companies to attempt high-risk, high-reward opportunities while building contingency options."Generic competition is understandably more intense for blockbuster drugs, seemingly promising guaranteed riches for the generics manufacturers who make it to market with an cheap, attractive alternative. One year after patent expiry, the average blockbuster faces twice as many competitors as a typical drug with less staggering sales. Blockbusters also experience more severe sales deterioration, and can lose as much as 75 per cent of their previous market share in the 12 months following patent expiry. It's no wonder Pfizer is anxious over the imminent body blows Lipitor's patent expiry is likely to land from 2010.Though the challenges posed by generics companies are significant, there are not necessarily insurmountable. Innovator companies have a number of tools to hand which, if used wisely and with due appreciation of the time factor, can help preserve revenues and extend patent life.

Pfizer to outsource API from Hikal

Hikal Ltd. has completed a contract manufacturing agreement for supply of active pharmaceutical ingredients (API's) with Pfizer. Terms of the agreement were not disclosed.
"We are extremely pleased to be selected as a long term contract manufacturer by Pfizer", said Jai Hiremath, vice chairman & managing director of Hikal Ltd. "This agreement will have a substantial impact on our Pharmaceutical business in the coming years".
"We look forward to working with Hikal, a respected contract manufacturing company and are delighted that they are able to contribute towards supply of APIs for Pfizer products", said Peter Stevenson, vice-president, global contract manufacturing, procurement and Pfizer Centre Source, Pfizer Inc.
Hikal is a reliable long-term outsourcing partner to companies in the pharmaceuticals, agrochemicals and specialty chemicals industry. The company has been supplying key APIs and intermediates, manufactured using stringent global quality standards, for it's customers in the United States, Europe and Japan.Hikal's advanced manufacturing facilities have been inspected and approved by globally recognized bodies such as the US FDA. The API and pharmaceutical intermediates manufacturing facilities are situated in Jigani (Bangalore) and Panoli (Gujarat) respectively. The crop protection facilities are located at Taloja and Mahad (Maharashtra). Hikal's manufacturing activities are supported by state-of-the-art research centres and pilot plant facilities located at Bangalore and Taloja respectively.

Sciele Pharma got USFDA approval for new dosage strengths of nisoldipine formulation

The Atlanta, Georgia-based Sciele Pharma, Inc. has bagged US Food and Drug Administration (FDA) approval for the company's all four dosage strengths of the new Sular formulation. The new Sular (nisoldipine) formulation. Nisoldipine is an oral calcium-channel blocker (CCB) of the dihydropyridine (DHP) class. Other calcium channel blockers in the Dihydro Pyridine class, which utilises SkyePharma's patented Geomatrix technology, provides a lower dose of Sular for each of its current doses. The company is expected to launch the new Sular formulation during the first quarter of 2008.Patrick Fourteau, chief executive officer, Sciele Pharma, said, "We are excited about this approval by the FDA for the new Sular formulation. This validates our product development and regulatory capabilities, as we have become a fully integrated pharmaceutical company."Sciele Pharma, Inc. is a pharmaceutical company specialising in sales, marketing and development of branded prescription products focused on cardiovascular/metabolic, women's health and paediatrics. The company's cardiovascular/metabolic products treat patients with high cholesterol, hypertension, high triglycerides, unstable angina and type 2 diabetes. SkyePharma, using its proprietary drug delivery technologies, develops new formulations of known molecules to provide a clinical advantage and life-cycle extension. The company has eleven approved products in the areas of oral, inhalation and topical delivery.

Alkermes in agreement with Johnson & Johnson unit to sell naltrexone in Russia

Alkermes Inc. Monday said it entered into an exclusive agreement with a subsidiary of Johnson & Johnson to commercialize its naltrexone extended-release injectable suspension drug in Russia and other countries in the Commonwealth of Independent States.Vivitrol is used in the treatment of alcohol and opioid dependence.Under the terms of the agreement, Cilag GmbH International, a unit of Johnson & Johnson, plans to make an upfront payment of $5 million to Alkermes. It also will pay up to an additional $34 million upon the meeting of certain milestones, including regulatory approval, certain agreed-upon events, and sales levels for Vivitrol.Cilag has primary responsibility for filing the new drug application in Russia and the other territories. Alkermes will be responsible for manufacturing the drug, in return for manufacturing revenue and the sales royalty.

JAZZ PHARMACEUTICALS, INC. ANNOUNCES RECEIPT OF FDA ORPHAN DRUG DESIGNATION FOR RECURRENT ACUTE REPETITIVE SEIZURES PRODUCT CANDIDATE

Jazz Pharmaceuticals, Inc. (In a press release) announced today that it has received orphan drug designation from the U.S. Food and Drug Administration (FDA) for its JZP-8 product candidate for the treatment of recurrent acute repetitive seizures. In December 2007, Jazz Pharmaceuticals dosed the first patient in a Phase II clinical trial of JZP-8.JZP-8 is a novel drug delivery formulation incorporating clonazepam, a widely prescribed benzodiazepine. The product candidate is designed to be a fast-acting intranasal spray for the treatment of recurrent acute repetitive seizures in patients with epilepsy. Jazz Pharmaceuticals previously completed development activities to select the active pharmaceutical ingredient for the product, to determine its formulation, and to assess its safety and tolerability in early stage studies."JZP-8 is one of the first development product candidates from our internal product identification and development program to enter Phase II," said Samuel R. Saks, M.D., Chief Executive Officer of Jazz Pharmaceuticals. "Dosing of the first patient in our Phase II clinical trial and receipt of orphan drug designation are important milestones for this program."

OrphanDrug Designation for the non-radiolabeled version of anti-cancercompound TM601

TransMolecular, Inc., a biotechnology company focused on targetedtherapies for cancer, today announced that the FDA has granted OrphanDrug Designation for the non-radiolabeled version of its anti-cancercompound TM601, which is currently entering clinical trials for thetreatment of malignant glioma. The company had previously receivedOrphan designation for the radiolabeled version, 131I-TM601, whichrecently completed patient enrollment in a Phase 2 clinical trial inglioma and a Phase 1 trial in multiple tumor types. TM601 is a synthetic version of chlorotoxin, a naturally occurringpeptide derived from scorpion venom, which is highly specific intargeting both primary tumors and metastases. TM601 targets and bindsto receptors expressed on tumor cells but not on normal, healthycells. As TM601 binds primarily with the tumor cell receptor sites, italso delivers a targeted dose of radiation, killing the tumor cellwithout affecting nearby healthy cells. The data obtained frompreclinical and clinical data also suggest that native TM601 mayaffect a tumor's ability to grow and spread without added radiation,so the therapeutic potential as a non-radiolabeled peptide is alsobeing explored. The Company's robust development plan for TM601reflects its broad platform potential for multiple applications incancer. The FDA has granted it orphan drug status for patients withhigh-grade and malignant glioma, as well as a Fast Track designation.

"We are pleased to receive orphan drug status for TM601 inmalignant glioma," stated Michael Egan, President and Chief ExecutiveOfficer of TransMolecular. "The TM601 platform has performed very wellin recent Phase 1 and 2 clinical trials, showing specific tumortargeting in both primary and metastatic disease of multiple tumortypes. This adds to a strong clinical rationale supporting itstherapeutic promise, and we look forward to initiating Phase 1clinical trials with the non-radiolabeled form of this drug candidatein malignant glioma. This designation is part of TransMolecular'sstrategy to advance this program so that patients with thispoor-prognosis disease may eventually have a new treatment optionavailable to them." The FDA grants Orphan Drug Designation to promising products thataddress rare diseases affecting fewer than 200,000 Americans annually.If non-radiolabeled TM601 receives FDA approval for malignant glioma,this designation will entitle TransMolecular to exclusive marketingrights for the compound for the treatment of malignant glioma forseven years following the NDA approval. Orphan Drug Designationprovides financial and regulatory incentives for companies pursuingless common diseases. About TM601

Pfizer finalize deal on Schizophrenia drug

Pfizer Inc said on Monday it finalized a deal with Japan's Taisho Pharma to jointly research and develop TS-032, a new schizophrenia drug discovered by Taisho.
Taisho will grant Pfizer exclusive development and commericalization rights for the drug outside Japan. Pfizer said it will pay Taisho an initial payment of $22 million, as well as royalties and milestone payments depending on whether the drug is approved by regulators and is launched

UK goverment in process of 10% drug price cut

The UK government is seeking a cut of 10 percent in the prices the state-run National Health Service pays for prescription medicines, the Financial Times reported on Monday.
Health minister Alan Johnson told the paper he planned to generate substantial savings in the drugs budget during talks to be completed by June on the agreement that covers the price to the health service of branded drugs.
Johnson said last August he planned to renegotiate the Pharmaceutical Price Regulation Scheme to ensure taxpayers get value for money.
The Financial Times said government officials were believed to have staked out an initial position with industry to cut the 11 billion pounds annual medicines bill by at least 10 per cent, or about 1 billion pounds.
The demand is part of the health department's efforts to make savings of 3 percent a year, imposed by the Treasury as part of the comprehensive spending review announced last year.
Britain is a major centre for drug research, although the local market represents only 3 to 4 percent of global drug sales, making it a relatively minor outlet for firms such as GlaxoSmithKline Plc and AstraZeneca Plc

Judge denies class in Fosamax(Alendronate sodium trihydrate) cases against Merck

A U.S. federal judge has denied motions to certify classes of users of osteoporosis drug Fosamax(Alendronate sodium trihydrate) who wanted Merck to set up a program to monitor them for an ailment involving jaw bone decay.
U.S. District Judge John Keenan in a ruling dated Thursday denied motions to approve classes of current and former users of the popular drug in Pennsylvania, Florida and Louisiana who have not been diagnosed with the ailment.
"The court finds that class-treatment of these claims is inappropriate because they present too many individual questions of fact particular to each class member's claim," Keenan wrote in a 41-page ruling.
More than 360 federal product liability cases have been filed against Merck by people who claim to have taken Fosamax, according to the ruling.
They allege that Fosamax caused the plaintiffs to either develop the ailment, known as osteonecrosis of the jaw, or to suffer an increased risk of developing the condition in the future, Keenan wrote.
Plaintiffs' lawyer Timothy O'Brien said funding the program in the three states would have cost Merck hundreds of millions of dollars. But he added that he expected Merck's liability on the personal injury cases would exceed that.
O'Brien, of law firm Levin Papantonio, estimated that the number of cases in federal and state courts would increase to 1,500 to 2,000 by the end of the year from roughly 460 now.
The first federal cases are expected to go to trial at the end of the year, O'Brien said.
Merck's lawyer, Paul Strain, said the company is defending the lawsuits vigorously.
"We believe that there is no scientific evidence establishing that Fosamax causes this condition," Strain said. "We believe we have meritorious defenses."
Merck expects Fosamax sales of about $3 billion for 2007, but the company expects sales to fall dramatically in 2008 as generic rivals hit the market.

Glaxo sued Barr over Argatroban injection

GSK, Mitsubishi and Encysive Pharma have filed a patent infringement lawsuit to stop Barr Laboratories from producing a generic version Argatroban injections.The suit was filed on Dec. 28 in the U.S. District Court for the Southern District of New York after Barr submitted an ANDA, with the USFDA to market a generic version of the injections.Argatroban is approved by the FDA to treat thrombocytopenia induced by popular blood thinner Heparin. The drug is also used in patients undergoing heart procedures.Encysive holds the approved NDA for Argatroban and has licensed the North American marketing rights for the drug to GlaxoSmithKline. Mitsubishi Chemical, whose pharmaceutical arm Mitsubishi Tanabe Pharma Corp. is also named as a plaintiff in the suit, holds US5214052 (which covers method for dissolving an arginineamide, comprising: dissolving 2-arylsulfonyl-L-argininamide and/or its salt in a solvent containing ethanol, water and a saccharide) for the injection.Barr filed its ANDA with the FDA in September 2007. Two months later, Barr notified Encysive of its application, which seeks marketing approval before Mitsubishi Chemical's patent expires in June 2014.Barr claims the patent is invalid, unenforceable and would not be infringed by its manufacture and sale of a generic copy. Barr's invalidity claims are based on a prior European patent application and a paper published in the Journal of the American Pharmaceutical Association in 1951.“Beyond summarily claiming that 'the '052 patent is invalid, unenforceable, and/or will not be infringed by the proposed product, Barr does not specifically assert that the '052 Patent is unenforceable, and the letter does not provide any factual or legal basis for an assertion that the '052 patent is unenforceable, as required by applicable law,” the complaint said.Barr believes it is the first company to file an ANDA containing a paragraph IV certification for Argatroban. If the FDA approves the application, Encysive would have a 180-day exclusive window to market generic Argatroban.Encysive said the lawsuit would automatically stay the FDA from approving Barr's ANDA for 30 months unless modified by the court.The patent, titled “Method for dissolving arginineamides and pharmaceutical compositions containing them,” was issued in May 1993 and assigned to Mitsubishi Chemical. Encysive's New Drug Application was approved by the FDA in June 2000.Barr said that the Argatroban injection product produced sales of $111 million in the U.S. for the 12 months ended October 2007, based on IMS sales data.

Daiichi Sankyo, Lilly Submit NDA for Investigational Antiplatelet Drug, Prasugrel

Daiichi Sankyo Company, Limited and Eli Lilly and Company today announced that on Wednesday, Dec. 26, 2007, they submitted a New Drug Application for prasugrel to the USFDA. Prasugrel is an oral antiplatelet agent, initially in development for the treatment of patients with acute coronary syndrome who are managed with percutaneous coronary intervention (PCI), including coronary stenting.
If approved for marketing in the United States, the trade name for prasugrel will be Effient company officials added."We are elated," said J. Anthony Ware, M.D., Lilly vice president and cardiovascular/acute care platform leader for prasugrel. "We feel confident in the strength and completion of this submission package, and plan to complete our submission in Europe in the first quarter of 2008. The benefit/risk profile of this compound, in comparison with the current standard of care, has the potential to improve outcomes for ACS patients undergoing PCI."

Takeda Submitted NDA for novel antidiabetic agent

Takeda (in a press release) announced today that Takeda Global Research & Development Center, Inc. submitted a New Drug Application to the USFDA for alogliptin (development code: SYR-322), a highly selective dipeptidyl peptidase-4 (DPP-4) inhibitor under investigation for the treatment of type 2 diabetes. Discovered by Takeda San Diego, Inc., alogliptin was designed to selectively inhibit DPP-4 taken orally once daily.

DPP-4 inhibitors are a new class of oral agents for the treatment of type 2 diabetes, which slow the inactivation of incretin hormones GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic peptide). The incretins play a major role in regulating blood glucose levels and may have the potential to improve pancreatic beta-cell function.
The NDA submission was supported by six Phase 3 clinical trials involving over 2,000 patients conducted in 220 centers worldwide. The safety and efficacy of alogliptin was studied as a once-daily monotherapy adjunct to diet and exercise and as an add-on therapy to other antidiabetic medications including sulfonylureas, metformin, thiazolidinediones (TZDs), and insulin. In the studies, alogliptin was associated with statistically significant reductions in hemoglobin A1c, which reflects average blood glucose concentration over the previous two to three months. Alogliptin was generally well-tolerated and weight neutral. There was no increase in hypoglycemia compared to placebo.
"The NDA submission for alogliptin is a significant milestone for Takeda, as it has the potential to position us as one of the global leaders in diabetes treatment," said Yasuchika Hasegawa, president of Takeda. "Takeda's continued growth, now and in the future, will be based on our ability to focus and have success in this therapeutic area. Our hope is that alogliptin will become an important treatment option for patients with type 2 diabetes and the healthcare providers who treat them."GLP-1 and GIP are produced by the digestive tract in response to food, and regulate glucose balance, primarily by stimulating glucose-dependent insulin secretion. In addition, GLP-1 suppresses pancreatic glucagon secretion and subsequent liver glucose production, enhances glucose disposal, slows gastric emptying, and elicits satiety, a feeling of fullness.

Obesity Drug Makers and market

NEW YORK (Associated Press) - The race for a magic weight-loss pill will heat up in 2008, with several major pharmaceutical companies expected to release key clinical trial data on drugs that appear to generate more weight loss than anything now on the market.
The diet industry is a multibillion-dollar enterprise, with companies such as WeightWatchers, Nutrisystem and Medifast kicking off the year by marketing diet and behavioral changes to consumers who have made losing weight their top New Year's resolution.
But the quest hasn't abated for a long-term weight-loss solution in the form of a pill capable of solving the nation's growing obesity epidemic.
In the U.S., Europe and Japan, the market for weight-loss drugs totaled about $600 million in 2005, and is expected to surge globally to roughly $2 billion in 2010, according to a recent report from drug industry market information provider Espicom Healthcare Intelligence.
Clearly people will pay whatever it takes to lose weight without restrictive diets and exercise, and the company that can make that happen could bring in billions.
"Doctors and patients tell us there is tremendous interest in a medicine that can provide safe, double-digit weight loss," said Daniel M. Bradbury, president and chief executive of San Diego-based Amylin Pharmaceuticals Inc., which is heavily pursuing drugs for obesity.
About half a dozen drugs are currently available by prescription for weight loss and obesity including Roche Laboratories Inc.'s Xenical and Abbott Laboratories' Meridia (Sibutramine). But weight loss with current drugs is rarely more than 10 percent, and these products can cause unpleasant side effects.
British drug maker GlaxoSmithKline had some success in 2007 with its over-the-counter weight-loss drug Alli, which like Xenical eliminates a portion of ingested fat before it can be stored in the body. Glaxo reported third-quarter sales of its over-the-counter drugs grew 24 percent to 417 million pounds (US$827.5 million), boosted in part by the launch of Alli in the U.S.
But competition is rising, with at least 30 companies now targeting the market, particularly with combinations of drugs currently for sale. Pfizer Inc. and Bristol-Squibb recently teamed up to develop DGAT-1 inhibitors, or compounds that target the DGAT enzyme critical to the creation of triglycerides and fat storage. Other vying for a piece of the obesity drug market include Orexigen Therapeutics Inc., Novo Nordisk A/S, Merck & Co., Arena Pharmaceuticals Inc., Vivus Inc. and Athersys Inc.
"Overall what we're starting to see is the use of combination products that could approach the levels of efficacy of some surgeries, and that's unprecedented," said Lazard Capital Markets analyst Matthew Osborne in an interview. "If you're seeing greater than 15 to 20 percent weight loss, that is a significant benefit over the existing class of drugs, which show around 5 percent weight loss and short-lived results."
San Diego-based Arena Pharmaceuticals Inc. has an obesity product, Lorcaserin, already in late-stage trials. In March, the company is expected to report critical safety results. The drug, which hasn't shown safety issues so far, has been under intense scrutiny by analysts who are concerned about its marketing viability, since Lorcaserin is said to work similarly to now discontinued Fen-Phen, which caused heart problems.
Meanwhile, Amylin has seen success with its diabetes drug Byetta, after patients reported weight loss as a welcomed side effect, prompting doctors to prescribe it off-label to overweight patients. Amylin now is pursuing another diabetes drug, Symlin (pramlintide), for obesity, in combination with other hormones and already available obesity drugs.

Pfizer to Appeal Canadian Federal Court Ruling on Lipitor Patent

Pfizer (in a press release) said today it will appeal a Canadian Federal Court decision in favor of generic manufacturer Apotex in its challenge to a Pfizer patent covering Lipitor.
The court denied Pfizer's request to prevent Apotex from launching a generic version of Lipitor prior to the expiration of Pfizer's enantiomer (calcium salt) patent in July 2010. The court's decision has no immediate commercial impact because Lipitor is protected by other patents in Canada, which also are the subject of pending legal challenges.
The ruling by the Federal Court has no impact on Lipitor patent litigation in other countries.

Watson Launches Generic Biaxin XL

Watson announced that it has launched Clarithromycin Extended-Release Tablets, USP in the 500 mg strength. Watson's Clarithromycin Extended-Release product is the generic equivalent to Abbott's Biaxin(R) XL, which is indicated to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. For the 12-months ending September 2007, Biaxin(R) XL and its generic equivalents had total U.S. sales of approximately $200 million, according to IMS Health data.
The U.S. Food and Drug Administration granted final approval of Watson's Abbreviated New Drug Application (ANDA) for Clarithromycin Extended-Release on June 24, 2004. Patent infringement litigation related to Watson's ANDA was dismissed with prejudice on July 12, 2007.

Public citizen sues FDA on Floxacin

The consumer group went to federal court today to force the agency to act on a petition filed last summer seeking stronger warnings about the risks of tendon rupture associated with fluroquinolones, a class of antibiotics used to treat bacterial infections. These includes Levaquin, a Johnson & Johnson med, and Bayer’s Cipro, along with other brand name versions and various generics. (lawsuit).
Although the labels warn of tendon ruptures, Public Citizen wants the FDA to place Black Box warnings on the drugs. J&J has said it believes the current tendon warning is adequate while Schering-Plough, which markets Cipro in the US as part of an agreement with Bayer, has said it won’t comment on Public Citizen’s petition.
The consumer group complains that the warning is buried a list of possible adverse reactions to the drugs and, therefore, is inadequate. Meanwhile, tendon injuries related to the drugs continue at an “alarming rate,” Public Citizen charges.
In a review of the FDA’s adverse event database, Public Citizen found 262 cases of tendon ruptures, 258 cases of tendonitis and 274 cases of other tendon disorders reported between November 1997 and December 2005 associated with the drugs, according to the lawsuit. Of those, 175 occurred since 2003. About 61 percent of the reported tendon problems were associated with Levaquin and 23 percent were associated with Cipro, Dow Jones writes. Since 2005, Public Citizen says an additional 74 tendon ruptures have been reported to the FDA.
“While the FDA sits idly by and ignores the problem, more people will suffer serious tendon ruptures that could have been prevented,” says Sid Wolfe of Public Citizen. “The current warning is buried in a long list of possible adverse reactions and is far too easy to miss.”

Generic approvals (DuoNeb and Granisetron)

Albuterol Sulfate and Ipratropium Bromide
Teva announced today that the USFDA has granted final approval for the Company's Abbreviated New Drug Application (ANDA) to market its generic version of Dey's bronchodilator, DuoNeb(R) (Albuterol Sulfate and Ipratropium Bromide) Inhalation Solution, 3 mg (0.083%) and 0.5 mg (0.017%). Shipment of the product will begin immediately.
The brand product had annual sales of approximately $265 million in the United States for the twelve months ended September 30, 2007, based on IMS sales data.
Granisetron hydrochloride
Barr Pharmaceuticals, Inc. today announced that its subsidiary, Barr Laboratories, Inc. has received final approval from the U.S. Food and Drug Administration (FDA) for its generic version of Roche Laboratories Inc.'s Kytril (granisetron hydrochloride) Tablets, 1mg (eq to 1 mg base). The Company received final approval following the expiration of Roche's patent on December 28, 2007, and plans to launch its product shortly.
KYTRIL (granisetron hydrochloride) Tablets, 1 mg (eq to 1 mg base) is indicated for the prevention of: nausea and vomiting associated with initial and repeat courses of emetogenic cancer therapy, including high-dose cisplatin; and, nausea and vomiting associated with radiation, including total body irradiation and fractionated abdominal radiation. The product had annual sales of approximately $88 million for the twelve months ended October 2007, based on IMS sales data

Barr Confirms Patent Challenge of Argatroban

Barr today confirmed that its subsidiary, Barr Laboratories, Inc., has initiated a challenge of the patent listed by Encysive Pharmaceuticals in connection with its Argatroban(R) Injection (argatroban) 100mg/mL, 2.5mL vial. The Company believes that it is the first to file an Abbreviated New Drug Application (ANDA) containing a paragraph IV certification for Argatroban. Encysive Pharmaceuticals, Inc. is the holder of the New Drug Application (NDA) for Argatroban, which is manufactured for the U.S. market by GlaxoSmithKline for Encysive.
Barr filed its ANDA containing a paragraph IV certification for a generic Argatroban product with the USFDA in September 2007, and received notification of the application's acceptance for filing in November 2007. Following receipt of the notice from the FDA, Barr notified the New Drug Application (NDA) holder and patent owner.
Inc. announced that Mitsubishi Chemical Corporation, the patent holder for Argatroban injections, Mitsubishi Tanabe Pharma Corporation, Encysive and GlaxoSmithKline had filed suit in the U.S. District Court for the Southern District of New York to prevent Barr from proceeding with the commercialization of its product. This action formally initiates the patent challenge process under the Hatch-Waxman Act.
Argatroban(R) Injection (argatroban) 100mg/mL, 2.5mL vial is indicated as an anticoagulant for prophylaxis or treatment of thrombosis in patients with heparin-induced thrombocytopenia, and as an anticoagulant in patients with or at risk for heparin-induced thrombocytopenia undergoing percutaneous coronary intervention (PCI). The product had sales of approximately $111 million in the U.S., based on IMS sales data for the twelve months ended October 2007.

Biovail Announces Supply Agreement for Commercialization of Tramadol (ER)

Biovail Corporation (In a press release) today announced that a subsidiary, Biovail Laboratories International SRL, has entered into an exclusive supply agreement with Janssen Pharmaceutica NV (Janssen), a division of Johnson & Johnson, for the marketing and distribution of Biovail's once-daily, extended-release formulation of tramadol hydrochloride in 86 countries in two regions - Central and Eastern Europe/Middle East and Latin America.
Under the terms of this agreement, which has a 10-year term, Biovail will manufacture and supply once-daily extended-release tramadol hydrochloride tablets in dosage strengths of 100mg, 200mg and 300mg to Janssen at contractually determined prices. Janssen affiliates will be responsible for all related promotional costs, as well as all regulatory filings and the management of the regulatory approvals process.

Lundbeck buys alcoholism drug rights in UK, Ireland

Danish pharmaceutical group Lundbeck has acquired the UK and Ireland rights for alcoholism drug nalmefene from Britannia Pharmaceuticals, a unit of Germany's STADA Arzneimittel AG
The drug was developed by Finnish biotechnology company BioTie Therapies Corp, which has been selling the rights to it country by country.
Lundbeck now owns worldwide rights to the drug excluding North America, Mexico, Turkey and South Korea. It plans to conduct additional Phase III studies with nalmefene this year before applying for marketing authorisation in the European Union.

FDA approves Watson respiratory drug

Drug developer Watson said that the Food and Drug Administration approved its generic version of Dey LP's respiratory condition treatment DuoNeb.Duoneb is a combination of two bronchodilators, Albuterol Sulphate and Ipratropium Bromide. It is used to treat symptoms (ie, bronchospasms) in patients with lung disease (ie, chronic obstructive pulmonary disease or COPD). It is commonly administered using a nebulizer.
Duoneb is marketed by Dey, L.P. (Napa, California) under the brand name DuoNeb®. It is available as a fluid (for use with a nebulizer).

AstraZeneca submits sNDA for Quetiapine

AstraZeneca (In a press release) said it had submitted two supplemental new drug applications to the USFDA for its drug Seroquel (quetiapine), which is currently used in the treatment of schizophrenia.The applications seek approval for the drug to be used in the treatment of manic episodes associated with bipolar disorder, as well as bipolar depression. The Wilmington, Del.-based pharmaceutical company said the submissions were based on a clinical studies that met their primary endpoint. In the studies, the effect of Seroquel was compared to a placebo in the changing of the young mania rating scale, and Montgomery Asberg depression rating scale, in patients.AstraZeneca said it would presents the results of the study at a scientific congress later in 2008

FDA approves new formulation of metformin hydrochloride

Specialty drugmaker Depomed Inc. said Wednesday the USFDA approved a new formulation of the company's diabetes drug Glumetza.

GLUMETZA™ (metformin hydrochloride extended release tablets) is indicated alone or in combination with sulfonylurea or insulin as an adjunct to diet and exercise to improve glycemic control in patients 18 years of age and older with type 2 diabetes.

The FDA approved a 1g tablet, adding to the 500-milligram dose already on the market. The maximum effective dose is about 2,000-milligrams per day, the company said, making the newly approved dose an option for patients looking to take fewer tablets each day.
The drug is used to treat type 2 diabetes, the most common form of the disease.

Sun files Para IV against Entacapone product patent

Sun Pharma informed Orion Corporation that it has amended its Abbreviated New Drug Application (ANDA) with the USFDA seeking authorisation to produce and market generic versions of Stalevo tablets 25/100/200 mg and 37.5/150/200 mg strengths of carbidopa/levodopa/entacapone in the United States. Sun's amendment to its ANDA involves a Paragraph IV challenge to Orion's US5446194, which covers N,N-diethyl-2-cyano-3-(3,4-dihydroxy-5-nitrophenyl)acrylamide as product (Entacapone) generically as well as specifically. Entacapone is a catechol-O-methyl transferase inhibitor for the treatment of Parkinson's disease. When administered in conjunction with dopaminergic agents such as L-DOPA, entacapone increases the bioavailability of these compounds by facilitating their passage across the blood-brain barrier

The ANDA review process has recently just begun and the realisation of generic competition is neither certain nor imminent. Stalevo is an enhanced levodopa treatment originated by Orion Corporation and marketed in the United States by its exclusive licensee, Novartis, for the treatment of Parkinson's disease.

Sun previously filed Paragraph IV certifications against Orion's U.S. Patents US6500867 and US6797732, and Orion subsequently sued Sun (November 2007) in the United States for patent infringement. Of the six Orion patents listed in the FDA's Orange Book, three have not received Paragraph IV certifications from Sun (US4,963,590, US5,112,861, and US5,135,950), and the latest of these expires 31 October 2010. Paragraph IV certifications are not uncommon in the USA. Orion is, together with Novartis, currently evaluating its legal options to protect its rights. Under the U.S. system, if a patent owner brings a lawsuit against an ANDA applicant within a certain time limit, there will be a 30-month stay of final FDA approval. During that time, the FDA can give only a tentative approval to the ANDA applicant unless the applicant obtains a favorable decision on all challenged patents in the lawsuit India (Sun), has amended its Abbreviated New Drug Application (ANDA) with the USFDA seeking authorisation to produce and market generic versions of Stalevo tablets 25/100/200 and 37.5/150/200 mg strengths of carbidopa/levodopa/entacapone in the United States. Sun's amendment to its ANDA involves a Paragraph IV challenge to Orion's US 5446194. The ANDA review process has recently just begun and the realisation of generic competition is neither certain nor imminent. Stalevo is an enhanced levodopa treatment originated by Orion Corporation and marketed in the United States by its exclusive licensee, Novartis, for the treatment of Parkinson's disease. Sun previously filed Paragraph IV certifications against Orion's U.S. Patents US6500867 and US6797732, and Orion subsequently sued Sun (November 2007) in the United States for patent infringement. Of the six Orion patents listed in the FDA's Orange Book, three have not received Paragraph IV certifications from Sun (US4,963,590, US5,112,861, and US5,135,950), and the latest of these expires 31 October 2010

Generic Colazal (balsalazide disodium)

Mylan announced that USFDA has approved balsalazide disodium ANDA, which is a generic version of Salix Pharmaceuticals Ltd.'s key drug Colazal.
The drug treats ulcerative colitis, which is an inflammation of the rectal and colon lining that causes bleeding, frequent bowel movements and diarrhea. Colazal sales climbed to $31.1 million during the third quarter and accounted for nearly half of Salix's revenue.
Mylan's generic Colazal will enter the market against generic versions from Apotex and Roxanne, which also got FDA approval. Salix has partnered with Watson Pharmaceuticals Inc. to make a generic version of Colazal, in an attempt to offset the impact of wider competition.

Watson pharma to market authorized generic of Colazal
Pursuant to a supply and distribution agreement with Salix Pharmaceuticals, Ltd, Watson Pharma, Inc, will market and sell an authorized generic of Colazal (balsalazide disodium) capsules 750 mg, the company's anti-inflammatory drug approved for the treatment of mildly to moderately active ulcerative colitis. Watson will launch the authorized generic product immediately.Carolyn Logan, president and chief executive officer, stated, "Salix is committed to aggressively protecting its Colazal business and growing market share in the inflammatory bowel disease market. As part of our life cycle management program for Colazal, we are extremely pleased to partner with Watson to market and sell the authorized generic of Colazal. Watson is a major supplier of generic pharmaceutical products, and, with decades of experience and impressive expertise in the generics business, should be positioned to maximise our generic business."Salix Pharmaceuticals, Ltd., headquartered in Raleigh, North Carolina, develops and markets prescription pharmaceutical products for the treatment of gastrointestinal diseases. Salix's strategy is to in-license late-stage or marketed proprietary therapeutic drugs, complete any required development and regulatory submission of these products, and market them through the company's 150-member gastroenterology specialty sales and marketing team.Colazal (balsalazide disodium) capsules 750 mg, is an anti-inflammatory drug approved for the treatment of mildly to moderately active ulcerative colitis. Safety and effectiveness of Colazal beyond 12 weeks has not been established. Colazal was well tolerated in clinical studies. In clinical trials, patients reported the following adverse reactions most frequently: headache (8 per cent ); abdominal pain (6 per cent ); diarrhoea (5 per cent ); nausea (5 per cent ); vomiting (4 per cent ); respiratory infection (4 per cent ); and arthralgia (4 per cent ). Withdrawal from therapy due to adverse reactions

Perrigo, Mylan and Ranbaxy got final approval to market Cetirizine Hydrochloride Tablets, 5 and 10 mg

Perrigo announced that it has received final approval from the USFDA for its Abbreviated New Drug Application (ANDA) for over-the-counter (OTC) Cetirizine Hydrochloride Tablets, 5 and 10 mg.The product will be marketed under store brand labels and is comparable to McNeil Consumer Healthcare's Cetirizine Hydrochloride Tablets, 5 and 10 mg, which will be marketed as Zyrtec(R) Tablets, indicated for allergy and hives relief. According to Wolters Kluwer data, brand sales for the original prescription strength version of the product for the 12 months ending October 2007 were approximately $1.4 billion.
Mylan Inc. today announced that Mylan Pharmaceuticals Inc. has received final approval from the USFDA for its Abbreviated New Drug Application (ANDA) for Cetirizine Hydrochloride Tablets (OTC), 5 mg and 10 mg.Cetirizine HCl Tablets are the generic version of Pfizer's Zyrtec(R) Tablets, which had U.S. sales of approximately $1.4 billion for the 12 months ending Sept. 30, 2007.This product will be shipped immediately.
Ranbaxy has received final approval from the USFDA to manufacture and market cetirizine hydrochloride tablets, 5 mg and 10 mg. The office of generic drugs, US Food and Drug Administration, has determined the Ohm formulation to be bioequivalent and have the same therapeutic effect as that of the reference listed drug zyrtec allergy tablets, 5mg and l0mg and zyrtec hives relief tablets, 5mg and 10mg by Pfizer Pharmaceuticals Inc. Total annual market sales for cetirizine hydrochloride tablets as a prescription only product were $1.3 billion (IMS - MAT: September 2007).Cetirizine hydrochloride is indicated for the temporary relief of runny nose, sneezing, itching of the nose or throat, and itchy, watery eyes due to hay fever or other upper respiratory allergies."We are pleased to receive this final approval for cetirizine hydrochloride tablets (OTC) 5mg and 10mg that have proven its clinical value and utility in both adults and children. We are pleased to offer this preferred formulation that will meet the needs of all patients who need this medication in response to allergic reactions. This OTC product formulation further expands our portfolio of affordable generic alternatives and will be launched immediately to all classes of trade," said Jim Meehan, vice president of sales and distribution for Ohm Laboratories Inc, a wholly owned subsidiary of RLL.Ohm, based in North Brunswick, New Jersey, is a wholly owned subsidiary of Ranbaxy Laboratories Limited (RLL), India's largest pharmaceutical company. Ohm is engaged in the sale and distribution of generic and branded private label, OTC products in the US healthcare system.

Niche market

There is a very good article in businessweek on niche market by MATTHEW PERRONE http://www.businessweek.com/ap/financialnews/D8TRUHKG0.htm

There is no quick remedy for what ails the pharmaceutical industry: a tougher environment for drug approvals and a dwindling pipeline of new medications.
But these twin challenges -- evidence that the heyday of blockbuster drug-development is over -- are forcing the industry to ponder big changes in the laboratory. The biggest, analysts say, is likely to be a shift toward finding treatments for patients with rare diseases, or unusual strains of common afflictions.
By focusing on boutique medications, analysts say, drug makers will arouse less scrutiny from regulators, who have become extra sensitive to the potentially fatal side effects of widely prescribed medications for ailments such as arthritis and diabetes. The growing need to market niche treatments is also dictated by the reality of the business, in that there are fewer widespread maladies for which a popular pill doesn't already exist.
A lot is riding on the industry's ability to navigate this transition. For years, drug makers such as Pfizer Inc. and Merck & Co. could count on new blockbuster drugs to deliver double-digit profit growth. In the last two years, however, patents expired on Pfizer's blood pressure treatment Norvasc, Merck's cholesterol drug Zocor and more than $40 billion worth of other drugs. Meantime, the Food and Drug Administration delayed or denied would-be blockbuster therapies made by Sanofi-Aventis SA, Wyeth and others.
With profit growth slowing across the pharmaceutical industry, Pfizer and GlaxoSmithKline PLC -- the world's first- and second-largest drug makers -- each announced plans in 2007 to lay off thousands of employees.
"The hurdle has been raised, there's no question about it," GlaxoSmithKline Chief Executive Jean-Pierre Garnier said during a conference call to discuss third-quarter earnings. "What is unclear is exactly how we should modify our drug development plans to meet this higher hurdle."
Garnier and other executives say the FDA has become an increasingly cautious gatekeeper for new drugs, especially those to treat widespread ailments that aren't necessarily life-threatening. And the regulatory environment will only get tougher in 2008, when new rules kick in that allow FDA to limit how widely drugs are promoted and distributed to patients and physicians.
Drug companies griping about an overbearing FDA is a familiar refrain, but data backs up their contention that the agency is quicker to issue warning labels.
The FDA announced nearly 70 new or updated black box warnings on previously approved drugs in 2007, more than twice as many as in 2004, according to government data compiled by Joyce Generali, director of the Drug Information Center at Kansas University Medical Center. The warnings are the most serious a drug can carry.
In the past year, the agency also balked at approving Sanofi-Aventis' highly anticipated obesity drug Zimulti and sent Novartis AG and Wyeth back to the lab for more safety studies on their treatments for diabetes and menopause. The FDA also flatly rejected Merck's arthritis drug Arcoxia, a follow-up to Vioxx, the best-selling pain medication pulled from the market in 2004 after links to heart attack and stroke were found.
The withdrawal of Vioxx triggered a flurry of congressional hearings, during which the agency's ability to resolve drug-safety problems came under fire.
Former FDA Commissioner Mark McClellan, who left the post in early 2004, said the pressure to hold drugs to a higher standard of safety has increased dramatically since Vioxx.
FDA staff reject the bar-raising theory, pointing out that the percentage of drugs approved to those submitted has held steady in recent years.
But the agency has approved just 16 first-of-a-kind drug applications this year, a 20-year low that is 36 percent below the annual average over the last decade. FDA approved 18 first-of-a-kind drugs in 2005 and 2006, down from 31 in 2004.
Those who track pharmaceutical trends say companies share responsibility for the new-drug drought.
The number of applications for innovative drugs submitted to FDA has steadily declined since the mid 1990s, falling from a high point of nearly 60 submissions in 1995 to figures in the low 20s for recent years.
Operating under a "just say no to risk," mantra, companies have chosen to tweak drugs already on the market rather than invest in the unknown, said Steve Brozak, an analyst with WBB Securities.
"No pharmaceutical executive has ever lost his job for saying no to a new drug project," Brozak said. "And no FDA employee has ever lost his job for saying no to a new drug application."
Most recent biopharmaceutical breakthroughs have been for drugs to treat smaller patient groups.
Biotech powerhouse Genentech Inc. has successfully developed cancer treatments tailored to patients' specific genetic makeup. Meanwhile, Cambridge, Mass-based Genzyme Corp. has built a multibillion-dollar business around expensive treatments for rare diseases.
Several major pharmaceutical companies are already spending more on innovative biotechnology.
In the last year, Roche Holding Ltd. and Merck separately agreed to pay $1 billion for the rights to research drugs designed to silence genes that trigger certain diseases. The companies are banking on the research yielding personalized medicines with fewer side effects.
Investment in experimental technology, however, isn't as widespread a reaction as Wall Street expected.
Biotech drug maker Biogen Idec Inc. surprised investors earlier this month, saying it could not find a buyer two months after putting itself up for sale. Analysts had speculated that Pfizer, GlaxoSmithKline and Novartis AG might be interested in the company.
There are some industry observers who, counterintuitively, believe the FDA will become more willing to approve experimental drugs when the new regulations go into effect because they will be able to react with greater force when safety issues arise.
But most see that as wishful thinking.
"The pendulum at FDA is going to be stuck at the conservative end," said Christopher Milne, of the Tufts Center for the Study of Drug Development. Eventually, Milne believes, drug companies will learn to deal with a more cautious FDA, but only because they won't have any other choice.