Two years ago, on June 23, 2005, the U.S. Food and Drug Administration approved the first “ethnic” drug. Called BiDil (pronounced “bye-dill”), it was intended to treat congestive heart failure—the progressive weakening of the heart muscle to the point where it can no longer pump blood efficiently—in African-Americans only. The approval was widely declared to be a significant step toward a new era of personalized medicine, an era in which pharmaceuticals would be specifically designed to work with an individual’s particular genetic makeup. Known as pharmacogenomics, this approach to drug development promises to reduce the cost and increase the safety and efficacy of new therapies. BiDil was also hailed as a means to improve the health of African-Americans, a community woefully underserved by the U.S. medical establishment. Organizations such as the Association of Black Cardiologists and the Congressional Black Caucus strongly supported the drug’s approval.
A close inspection of BiDil’s history, however, shows that the drug is ethnic in name only. First, BiDil is not a new medicine—it is merely a combination into a single pill of two generic drugs, hydralazine and isosorbide dinitrate, both of which have been used for more than a decade to treat heart failure in people of all races. Second, BiDil is not a pharmacogenomic drug. Although studies have shown that the hydralazine/isosorbide dinitrate (H/I) combination can delay hospitalization and death for patients suffering from heart failure, the underlying mechanism for the drug’s efficacy is not fully understood and has not been directly connected to any specific genes. Third, and most important, no firm evidence exists that BiDil actually works better or differently in African-Americans than in anyone else. The FDA’s approval of BiDil was based primarily on a clinical trial that enrolled only self-identified African-Americans and did not compare their health outcomes with those of other ethnic or racial groups.
So how did BiDil become tagged as an ethnic drug and the harbinger of a new age of medicine? The story of the drug’s development is a tangled tale of inconclusive studies, regulatory hurdles and commercial motives. BiDil has had a relatively small impact on the marketplace—over the past two years, only a few million dollars’ worth of prescriptions have been sold—but the drug has demonstrated the perils of using racial categories to win approval for new pharmaceuticals. Although African-Americans are dying from heart disease and other illnesses at younger ages than whites, most researchers believe the premature deaths result from a complex array of social and economic forces [see “Sick of Poverty,” by Robert Sapolsky; Scientific American, December 2005]. Some medical professionals and policy experts, however, have pointed to BiDil as proof that genetic differences can explain the health disparity. Worse, some pharmaceutical companies are now using this unfounded argument to pursue other treatments targeted at various ethnic groups, a trend that may segregate medicine and fatten the profits of drugmakers without addressing the underlying causes that are killing so many African-Americans before their time.
Birth of BiDil
The BiDil saga began more than 20 years ago with a pair of studies designed to gauge the effects of vasodilating drugs—which widen blood vessels—on heart failure, a debilitating and ultimately fatal disease that afflicts millions of Americans. Until then, doctors treated heart failure with diuretics (to reduce the accumulation of fluid that results from inadequate pumping) and digoxin (to increase the contraction of the heart muscle) but had little else at their disposal. In the early 1980s Jay Cohn, a cardiologist at the University of Minnesota, hypothesized that administering two vasodilators, hydralazine and isosorbide dinitrate, might ease the strain on weakened hearts by relaxing both the arteries and veins. Together with the U.S. Veterans Administration, Cohn designed and conducted two trials to assess this theory.