Japan's Astellas Pharma loses U.S. patent protection on its product patent US4894366 on Tacrolimus (Prograf), a major transplant drug, on 8th april 2008, amid worries that its market share may erode more quickly than expected despite only mild generic competition for such drugs in the past.
Tacrolimus (also FK-506 or Fujimycin) is an immunosuppressive drug whose main use is after allogenic organ transplant to reduce the activity of the patient's immune system and so the risk of organ rejection. It is also used in a topical preparation in the treatment of severe atopic dermatitis ("eczema"), severe refractory uveitis after bone marrow transplants, and the skin condition vitiligo. It is a 23-membered macrolide lactone discovered in 1984 from the fermentation broth of a Japanese soil sample that contained the bacteria Streptomyces tsukubaensis. The stakes are high for Astellas. Transplant drugs are often be taken for life, making them stable earners for drug companies and Prograf's $2 billion in annual sales is around one fifth of the firm's overall revenues. The U.S. market accounts for around half of Prograf's sales.
Tacrolimus was discovered in 1987 by a Japanese team headed by T. Goto, T. Kino and H. Hatanaka; it was among the first macrolide immunosuppressants discovered, preceded by the discovery of rapamycin (sirolimus) on Rapa Nui (Easter Island) in 1975. Like ciclosporin, it was found in a soil fungus, although it is produced by a type of bacteria, Streptomyces tsukubaensis. The name tacrolimus is reportedly derived from 'Tsukuba macrolide immunosuppressant'.
The drug is owned by Astellas Pharma Inc. (Merger of Fujisawa Pharmaceutical Co., Ltd. and Yamanouchi Pharmaceutical Co., Ltd. as of April 1, 2005) and is sold under the tradenames Prograf®, Advagraf, and Protopic®. It is sometimes referred to as FK-506, an early name relating to its action. It was first approved by the USFDA in 1994 for use in liver transplantation, this has been extended to include kidney, heart, small bowel, pancreas, lung, trachea, skin, cornea, bone marrow, and limb transplants.
Astellas has also suffered delays in the approval of a successor drug it has developed, further clouding the outlook its transplant drug business. But a risk of organ rejection from transplants will work in Astellas' favour. While other drugs can easily lose up to half their sales after a patent ends, doctors and patients dealing with the potential of organ rejection are expected to be reluctant to switch to a generic transplant drug. Basing their assumptions on slow generic inroads into Novartis' immunosuppressant cyclosporine when it went off patent, most analysts say they are forecasting annual sales declines of only around 10-15 percent for Prograf. In a market dominated by Prograf and Novartis' cyclosporine, Prograf commands about 60 percent of the immunosuppressant market for a class drugs known as calcineurin inhibitors. In new transplants, its holds market share of around 84 percent for kidney transplants, 90 percent for liver transplants and 63 percent for heart transplants.
Generic threat
It's not known how many or which generic firms are planning to launch their versions of Prograf, or when. It depends on whether big generic firms like Sandoz or Teva enter the market. If Novartis' unit Sandoz enters, then that's a major threat. Novartis has the experience with immunosuppressants and it could shift sales staff with that experience to Sandoz. A key turning point for Astellas could be late April when the USFDA is expected to send a letter indicating whether it is ready to approve Prograf's successor drug, Advagraf, for liver transplants. Advagraf, a modified release version of Prograf taken once a day by patients, has been approved in Europe but has had less success with U.S. health authorities. Prograf is taken twice a day. The FDA declined in January 2007 to approve Advagraf for heart transplants and requested data on kidney and liver transplants. Last month, it requested further information on Advagraf for kidney transplants, meaning that Advagraf will face delays of at least six months before receiving approval for that indication. Prograf's patent expires in Europe in June 2009 and in Japan in December 2010.
Tacrolimus (also FK-506 or Fujimycin) is an immunosuppressive drug whose main use is after allogenic organ transplant to reduce the activity of the patient's immune system and so the risk of organ rejection. It is also used in a topical preparation in the treatment of severe atopic dermatitis ("eczema"), severe refractory uveitis after bone marrow transplants, and the skin condition vitiligo. It is a 23-membered macrolide lactone discovered in 1984 from the fermentation broth of a Japanese soil sample that contained the bacteria Streptomyces tsukubaensis. The stakes are high for Astellas. Transplant drugs are often be taken for life, making them stable earners for drug companies and Prograf's $2 billion in annual sales is around one fifth of the firm's overall revenues. The U.S. market accounts for around half of Prograf's sales.
Tacrolimus was discovered in 1987 by a Japanese team headed by T. Goto, T. Kino and H. Hatanaka; it was among the first macrolide immunosuppressants discovered, preceded by the discovery of rapamycin (sirolimus) on Rapa Nui (Easter Island) in 1975. Like ciclosporin, it was found in a soil fungus, although it is produced by a type of bacteria, Streptomyces tsukubaensis. The name tacrolimus is reportedly derived from 'Tsukuba macrolide immunosuppressant'.
The drug is owned by Astellas Pharma Inc. (Merger of Fujisawa Pharmaceutical Co., Ltd. and Yamanouchi Pharmaceutical Co., Ltd. as of April 1, 2005) and is sold under the tradenames Prograf®, Advagraf, and Protopic®. It is sometimes referred to as FK-506, an early name relating to its action. It was first approved by the USFDA in 1994 for use in liver transplantation, this has been extended to include kidney, heart, small bowel, pancreas, lung, trachea, skin, cornea, bone marrow, and limb transplants.
Astellas has also suffered delays in the approval of a successor drug it has developed, further clouding the outlook its transplant drug business. But a risk of organ rejection from transplants will work in Astellas' favour. While other drugs can easily lose up to half their sales after a patent ends, doctors and patients dealing with the potential of organ rejection are expected to be reluctant to switch to a generic transplant drug. Basing their assumptions on slow generic inroads into Novartis' immunosuppressant cyclosporine when it went off patent, most analysts say they are forecasting annual sales declines of only around 10-15 percent for Prograf. In a market dominated by Prograf and Novartis' cyclosporine, Prograf commands about 60 percent of the immunosuppressant market for a class drugs known as calcineurin inhibitors. In new transplants, its holds market share of around 84 percent for kidney transplants, 90 percent for liver transplants and 63 percent for heart transplants.
Generic threat
It's not known how many or which generic firms are planning to launch their versions of Prograf, or when. It depends on whether big generic firms like Sandoz or Teva enter the market. If Novartis' unit Sandoz enters, then that's a major threat. Novartis has the experience with immunosuppressants and it could shift sales staff with that experience to Sandoz. A key turning point for Astellas could be late April when the USFDA is expected to send a letter indicating whether it is ready to approve Prograf's successor drug, Advagraf, for liver transplants. Advagraf, a modified release version of Prograf taken once a day by patients, has been approved in Europe but has had less success with U.S. health authorities. Prograf is taken twice a day. The FDA declined in January 2007 to approve Advagraf for heart transplants and requested data on kidney and liver transplants. Last month, it requested further information on Advagraf for kidney transplants, meaning that Advagraf will face delays of at least six months before receiving approval for that indication. Prograf's patent expires in Europe in June 2009 and in Japan in December 2010.
