In a much discussed (see Kevin MD and Medical rants) study presented at the AHA meetings in New Orleans and just being published in this week’s NEJM, a fixed dose combination of hydralazine and isosorbide dinitrate, BiDil, was found to significantly reduce morbidity and mortality in African American patients with congestive heart failure. BiDil (vs placebo) was added to standard therapy for CHF (including ACE inhibitors or ARB’s, aldactone and beta-blockers). The trial was halted early because of significant benefit of the active medication.
This trial is being actively discussed because it seems to be the first time that a drug is being promoted specifically for use in a racial group. Another aspect of this study which I find fascinating is its financial genesis. My understanding of the course of events is as follows.
Isosorbide dinitrate and hydralazine have been used for the treatment of heart failure in the past. The isosorbide-hydralazine combination pill was patented (in the 1980’s) for the treatment of congestive heart failure, but failed to provide significant benefits in large trials; as a result, the FDA would not approve it as a new medication. Subgroup analysis of the original trials, however, suggested benefit in black patients. The company NitroMed, which had acquired the rights to the combination, then applied for and received a new patent for it specifically for the treatment of heart failure in black patients. Unlike the original patent, which expires in 2007, the new one for the same medication is valid until 2020. Armed with this new patent, NitroMed sponsored the current trial. With the positive results just reported, the FDA is likely to approve BiDil for use in black patients.
My initial reaction to this whole story was that it represents a typical interaction between industry, the patent system and the FDA. There is a one-two punch with the patent system prolonging the drug company’s monopoly by granting a new patent for use in a subpopulation, which the FDA then protects by limiting approval of the medication to that subpopulation.
The other side of this coin, however, is that precisely this system led to a potential profit for NitroMed, which made sponsoring the trial financially attractive. The result is likely to be of benefit to many African Americans. A prime example of the strengths and problems with the pharmaceutical industry’s ties to regulatory agencies.