BiDil's approval gives little incentive for companies to base drugs on biological markers rather than race, experts warn.

Color blind: The heart drug BiDil is prescribed specifically for blacks, but others are already clamoring for it. Credit: Sandy Huffaker/KRT

The landmark approval of BiDil, a drug touted to treat heart failure specifically in blacks, has raised questions about the role of race-specific drugs in medical practice. Hearing early reports that the drug is already being prescribed to people outside the prescription guidelines, experts are calling for a biological marker that can better predict who will respond to the drug.

I would prescribe to non-African Americans who are already on standard therapy and not doing well . Flora Sam, Boston Medical Center

The US Food and Drug Administration (FDA) in June approved BiDil after studies showed that it improves mortality after heart failure by 43% among blacks; the drug was found to be ineffective in whites (N. Engl. J. Med. 351, 2049–2057; 2004). It is not yet clear why the drug should be more effective in blacks, but one theory holds that BiDil compensates for a nitric oxide deficiency common in this population.

“Being black increases the likelihood of having that physiology, but it's no guarantee,” says Jonathan Sackner-Bernstein, a member of the FDA advisory panel that recommended BiDil's approval. “Other people also respond nicely.”

Geneticists and ethicists contend that race is a poor indicator of the underlying genetic or biochemical differences among different populations and could be a proxy for social factors (Nat. Med. 10, 1266; 2004).

Manuel Worcel, chief medical officer of Massachusetts-based NitroMed, Bidil's manufacturer, says the company is actively looking for genetic, biochemical or physiological markers that can predict who will respond to BiDil. “I believe this will expand the patient population,” he says. Once the company identifies reliable markers, NitroMed aims to design a clinical trial that uses the biomarkers, rather than ethnicity, to select participants. Other researchers are meanwhile analyzing genetic data from a subset of participants in the original trial.

The FDA's prescription guidelines for BiDil are relatively broad, specifying the drug can be used for individuals with heart failure who identify themselves as black. But others are already asking their doctors about the drug—and some doctors are complying. “I would prescribe to non-African Americans who are already on standard therapy and not doing well,” says Flora Sam, a cardiologist who led a segment of the BiDil trial at the Boston Medical Center. She says she has no financial arrangements with the company.

The drug's label allows for the broadest possible patient base, notes Sackner-Bernstein. “I don't think the product insert gives NitroMed major incentives to do further studies,” he says. NitroMed set BiDil's price at $1.80 per pill, adding up to almost $10 per day, nearly double the cost of other heart-failure treatments.

BiDil is made up of two generic drugs, isosorbide dinitrate and hydralazine, an older blood pressure medication that has been associated with lupus, an autoimmune disorder three times more common among black women than white. Researchers conducting the BiDil trial did not routinely test for lupus, but report one case of the disorder among 518 trial participants. NitroMed officials say BiDil's hydralazine component is too small to be of concern, but more lupus cases may arise as the drug is used more frequently and for longer durations, says Sackner-Bernstein.