By James DeGiulio --
On August 2, patients with the rare Fabry disease petitioned the Department of Health and Human Services to exercise the "march-in" powers under the federal Bayh-Dole Act, and issue an open license to use patents needed to manufacture Genzyme's enzyme replacement drug Fabrazyme (see "Genzyme's Manufacturing Issues with Fabrazyme Prompt Patients to Petition HHS Secretary to Exercise Bayh-Dole "March-in" Rights"). Not surprisingly, in a letter to the patients' attorney C. Allen Black, Jr., the NIH denied the petitioners' request. Despite recognizing the situation as grave, the NIH found there is no manufacturer situated to readily acquire FDA approval to manufacture Fabrazyme even under a march-in license.
Genzyme, which produces Fabrazyme under an exclusive license from Mount Sinai Medical Center, has been unable to produce enough drug to treat the U.S. Fabry disease market since 2009 due to various manufacturing issues. Initially, Genzyme's bioreactors were contaminated by a virus, and later, vials for injection were produced containing foreign contaminates. Once the supply got so low that patients were rationed to only 30% of the recommended dosage and no newly diagnosed patients were eligible for therapy, the petition was brought by Fabry patients who asked HHS to grant an open license to U.S. Patent Nos. 5,356,804 and 5,580,757.
Francis Collins, the Director of the NIH, signed off on the determination opinion in the Fabrazyme case. The opinion presents a primer on the process for bringing a biological product to market, which requires "substantial time, effort, and resources, irrespective of any patent rights." A manufacturer must procure clinical materials, gather preclinical data, and ensure safety before FDA will approve an Investigational New Drug Application to authorize beginning clinical trials. Following sufficient clinical trials, the Biologic License Application must be approved by the FDA, whose review can take ten months at minimum (six with priority status). In light of the regulatory hurdles that another manufacturer would have to overcome even with a license to the Genzyme patents, the NIH determined that exercising march-in rights at this time would not address the lack of Fabrazyme supply because it would simply take too much time for FDA approval. Further, Genzyme has indicated that it expects the production of Fabrazyme to be back to full levels in the first half of 2011, which should address the shortage. The NIH has agreed to monitor the situation, and has requested that Mount Sinai provide monthly reports on Genzyme's manufacturing process, and will reconsider its opinion upon receiving any unfavorable updates.
Mount Sinai has also agreed with the NIH not to seek injunctions against any infringers of the Fabrazyme patents. Nonetheless, the petitioners plan to appeal the NIH decision and argue that the HHS approved the FDA rules that block companies from manufacturing the drug in a timely manner under Bayh-Dole, even thought the HHS controls the FDA and the NIH. If history is any indication, there may be something to the irony of their argument. This month marks the 30th anniversary of the Bayh-Dole Act, and the march-in provision has yet to be exercised in the three decades of the legislation's existence.