New Drug BiDil Approved for Heart Failure in Black Patients Only
Issue 218 It

The results of study are expected to lead to approval of the first drug specifically for a single ethnic group. The results validate the gamble by the company, NitroMed, to take a drug that had failed to win approval for general use and test it only on African-Americans, an approach that ignited controversy on the relevance of race to medicine.

Michael D. Loberg, the president and chief executive, said the company had been expecting the drug to be approved in early 2006 but would now be ready to introduce the drug in early 2005, if the Food and Drug Administration approves it that soon for use by blacks.

NitroMed has argued that blacks have a higher rate of heart failure than the American population as a whole and that they tend not to respond to some existing heart failure drugs as well as other groups. For NitroMed executives, those factors, and some earlier evidence that blacks respond better to the drug, which is called BiDil, justified a test of the drug just in that ethnic group.

NitroMed said that an independent committee of medical researchers overseeing patient safety in the trial decided it would be unethical to continue giving some patients a placebo because those getting the drug were living significantly longer. The trial, which began in 2001 and had enrolled about 1,050 of the 1,100 patients eventually intended to take part, was halted immediately and all the participating patients will be offered BiDil.

"It is a spectacular result," said Anne L. Taylor, a professor of medicine at the University of Minnesota and the chairwoman of the study. "It offers an additional treatment for a group of patients who traditionally, with standard medications, have not done as well."
The stock of NitroMed, a still unprofitable start-up company based in Lexington, Mass., rose 73 percent, or $4.31, to $10.21 yesterday. Early in the day it had climbed above $16. The company, incorporated in 1992, went public only last November, when its shares were first offered at $11.

Dr. Loberg said there were about 750,000 blacks with heart failure, a debilitating condition in which the heart does not pump enough blood. In all, there are about five million Americans with heart failure.

Heart disease in blacks tends to be linked more to hypertension than to arterial blockages that are a major cause in white heart patients. NitroMed says that blacks are also more likely to have a deficiency of nitric oxide. But some of the higher rate of heart failure in blacks could be explained by socio-economic factors or a lack of access to medical care.

Labels for some drugs already make note of racial differences. The label for Cozaar, a hypertension drug, notes that the drug’s effect in reducing blood pressure is "somewhat less" in blacks and that there was no evidence that the drug’s benefit of reducing heart attack, strokes and death in the overall population applied to blacks.
To help win over critics, NitroMed got the Association of Black Cardiologists to be a co-sponsor of the trial.
BiDil works by enhancing the level of nitric oxide, a chemical that is produced by the cells lining the blood vessels and that plays a role in dilating blood vessels and controlling blood pressure.

BiDil is a combination of two old generic drugs, neither of them approved for heart failure. Jay N. Cohn, a professor at the University of Minnesota School of Medicine, first thought of combining them to treat heart failure in the 1970’s, and a trial was conducted in the early 1980’s. BiDil is a combination of two drugs, isosorbide dinitrate and hydralazine. Isosorbide dinitrate is a nitric oxide donor. Hydralazine is an antioxidant and vasodilator agent, which means it dilates blood vessels and protects the nitric oxide formed by isosorbide dinitrate from deactivating.

Reviewing the data from the old trial, Dr. Cohn and NitroMed found that the drug had been remarkably effective in the subset of patients who were black. By contrast, the results in the white patients were not statistically significant. Based on the old data, NitroMed applied in 2000 for approval to use the drug for blacks. The F.D.A. said it would consider approval if NitroMed conducted another trial to confirm the results, according to the company. That was the trial that has just been halted. Data from the trial will be released in the fourth quarter.