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Drug Approved For Heart Failure In Black Patients
By Andrew Pollack, Market Place
July 20, 2004
Photo Courtesy of BBC News
Correction Appended
A drug aimed at treating heart failure specifically in black patients has proved so effective that the clinical trial in which it was being tested has been halted early, the company sponsoring the trial said yesterday.
The results are expected to lead to approval of the first drug specifically for a single ethnic group. They seem to 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. The company's stock soared on yesterday's announcement.
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.
Yesterday, 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. If all of them used the drug, sales could reach $1 billion a year, he said, although he declined to project what sales would actually be. In all, there are about five million Americans with heart failure.
Nitro Med's trial had become a focus of the debate over what role race should play in determining medical treatments. Some scientists say that race has little meaning and that specific genetic factor that cross racial lines determine who will get a disease or who will benefit from treatments.
But some doctors say that until those specific genetic factors are known, race can be a convenient classification because people of the same race tend to share certain genetic characteristics. And 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.
Clyde Yancy, a member of the association and part of the steering committee for the trial, said the study needed to be conducted because blacks had been under-represented in previous trials and there were questions about whether they should be given the existing drugs.
"We had an unmet medical need to further understand the issue and the question of heart failure in African-Americans," said Dr. Yancy, head of the heart failure and heart transplant programs at the University of Texas Southwestern Medical Center in Dallas.
Still, he said, he saw drawbacks. "There are many who believe that this is a dangerous slope to begin to define treatment decisions according to race," Dr. Yancy said. "I don't disagree with that."
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. NitroMed specializes in drugs related to nitric oxide. Besides the work on BiDil, it has a collaboration with Merck to develop nitric-oxide-based COX-2 inhibitors, a category of painkiller that also includes Vioxx from Merck. Enhancing such painkillers with nitric oxide could be a way to reduce gastrointestinal side effects.
It also has agreement with Boston Scientific to develop nitric-oxide-coated cardiovascular stents - meshlike devices that doctors use to prop open coronary arteries in hopes of preventing heart attacks.
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.
That trial showed the drug to have some effect, but the Food and Drug Administration rejected the drug, arguing the data were not strong enough. After Medco Research, a company that had licensed the drug, dropped it, the rights reverted to Dr. Cohn. NitroMed, which was interested because the drug fitted its focus on nitric oxide, licensed it in 1999.
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.
"This has been 30 years," Dr. Cohn said. "I have to feel that I am finally vindicated."
Questions still remain about the size of the potential market. Dr. Loberg said he thought sales of the drug would grow quickly because the trial tested BiDil for use in addition to other heart failure drugs. So BiDil would not be competing directly with those other drugs.
Some analysts on a conference call convened by NitroMed yesterday questioned whether the company would be able to protect BiDil from generic competition, since doctors could write two separate prescriptions for the generic components that make up BiDil. Dr. Loberg said that would be difficult because the generic drugs are not sold in the same doses as are used in BiDil.
Dr. Loberg said that when scientists analyze the trial results they will look for genetic characteristics that can predict which patients are most likely to benefit from the drug. If such markers are found, it would be possible to test people in other ethnic groups for those markers, perhaps extending use of the drug.
Correction: July 21, 2004, Wednesday
The headline of the Market Place column on the front page of Business Day yesterday, about a clinical trial for BiDil, a drug aimed at heart failure specifically in black patients, misstated the outcome. The trial was halted because the drug was so effective; the drug did not receive approval.
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