Panel Urges Heart Drug for African Americans
A Food and Drug Administration advisory panel unanimously recommended Thursday that the agency approve a prescription drug to treat congestive heart failure in African Americans -- the first time that a medication has been specifically intended for a racial group.
FDA officials, who generally follow the recommendations of the advisory panels, said the data presented on the drug, BiDil, pointed to a benefit for African Americans taking it, but no real advantages for whites.
“It is very unusual; it is precedent-setting,” said Dr. Steven E. Nissen, the panel’s chairman. “But it is the case that we are moving forward to genome-based medicine. It’s going to happen.”
But critics say that approving a drug for one race may falsely suggest a biological validity for cultural prejudice. And some have questioned the thoroughness of the data presented in support of the application.
“I’m not sure that skin tone is a great proxy for a biological trait,” said panel member Vivian Ota Wang, a geneticist at the National Human Genome Research Institute.
BiDil’s manufacturer, NitroMed Inc., based its request for approval on the results of a study that included only African American patients. But if the FDA approves the drug, doctors would be able to prescribe it for patients of any racial or ethnic background, even though it was recommended only for blacks. Latinos, many of whom have African ancestry, might be one of the first populations to try it.
The FDA’s decision on BiDil is expected soon.
The advisory panel’s 9-0 vote capped hours of lively discussion in which members debated whether race is fundamentally a social designation or is, in certain cases, an imperfect indicator of biological differences. During a portion of the meeting reserved for public testimony, many witnesses said the drug should be approved for all ethnic groups, not just blacks.
“There are competing thoughts here,” said Dr. Robert Temple, director of the FDA’s Office of Drug Evaluation.
“Some people are offended by the whole idea” of racially targeted drugs, he said. “Others say, ‘Why aren’t you doing more?’ ”
A combination of two generic medications -- isosorbide dinitrate and hydralazine hydrochloride -- BiDil dilates, or opens, blood vessels. Hydralazine works on arteries, while the other medication affects veins. BiDil is shorthand for bidilator, or two drugs that work together to relax blood vessels.
Congestive heart failure is a progressive weakening of the heart that affects its ability to pump blood and leads to a buildup of fluid in the lungs. Patients struggle with fatigue and shortness of breath, and often wake up in the middle of the night feeling as if they are suffocating.
“Not being able to breathe is one of the scariest things human beings can go through,” said panel chairman Nissen, a cardiologist at the Cleveland Clinic.
About 5 million Americans, 725,000 of whom are black, suffer from congestive heart failure. Odds of long-term survival are 50-50 at best. FDA officials indicated that the drug probably would be approved to treat the severe form of the disease, in which any form of exercise induces symptoms.
Approval of the drug could be a bonanza for NitroMed, a small pharmaceutical firm in Lexington, Mass. The company’s stock, which was up 10 cents Thursday and closed at $19.51, has been rising this week in anticipation of the positive recommendation, which came after trading ended. Although the company’s patent on BiDil for general use runs out in two years, it has a separate patent for the drug’s targeted use by African Americans that does not expire until 2020.
The drug was developed for the general population, but clinical trials failed to find benefits significant enough for FDA approval. Its developer, Dr. Jay Cohn of the University of Minnesota, told the panel Thursday that he looked again at the data and found that African Americans seemed to show much better results with the drug.
NitroMed returned to the FDA and proposed another trial, solely with African Americans as subjects. In that study of 1,050 patients, half were given BiDil in addition to standard therapies and half a placebo plus standard therapies. The BiDil group showed a 43% reduction in deaths and a 39% decline in first-time heart failure hospitalizations. When the results became apparent, the study was deemed a success and halted early.
The major safety concern with BiDil centered on lupus-like symptoms that emerged in a few patients taking the drug in the initial series of clinical trials -- the ones that led to the initial FDA rejection. In the subsequent tests with African Americans, patients were not generally tested for signs of lupus.
NitroMed scientists have not been able to conclusively prove why their medication seems to be especially effective with African Americans.
The leading hypothesis is that it counteracts a deficiency in nitric oxide, a substance that is naturally present in the body. Studies indicate that a deficiency in nitric oxide, which helps to keep blood vessels supple and maintain healthy levels of blood pressure, may be more prevalent among African Americans. Isosorbide dinitrate promotes the release of nitric oxide, the company says, while hydralazine hydrochloride helps to preserve the substance from being broken down in the body.
Although it is well known that drugs can have differing effects in people of various ethnic groups, several members of the FDA panel were skeptical of NitroMed’s claims about BiDil’s special effectiveness among blacks.
The drug was tested on people who identified themselves as African American, with no further attempt to pinpoint any common underlying genetic traits. Extensive research has established that variations in skin color and physical characteristics do not translate into major genetic differences.
“Depending on how far we go back,” panel member Wang noted, “we all probably originate on the continent of Africa.”
Wang, who is Asian American, asked NitroMed researchers if she would have been included in the study had she told them she was black. Yes, they said. Wang voted to approve the drug, but said it should be available to all patients.
“What I do not agree with is having [prescribing instructions] targeted to a specific group,” she said. “I do not find the evidence persuasive.”
Speaking on behalf of the Congressional Black Caucus during the public hearing, U.S. Virgin Islands Delegate Donna M. Christensen said she agreed wholeheartedly that race was not an indicator of significant genetic differences.
She urged approval nonetheless, saying, “BiDil can save thousands of lives and reduce untold suffering for African American heart failure patients and their families.”
About 25% to 30% of congestive heart failure patients are black, a proportion that is about double the African American share of the population. High blood pressure, which is more common among blacks than other racial groups, is a risk factor for developing the disease. Medical evidence indicates that blacks do not respond as well as whites to ACE inhibitors and other standard therapies for the chronic disease.
Some members of the advisory panel said they were not entirely convinced that NitroMed had proven the effectiveness of BiDil, and others were troubled by a lack of data on long-term safety.
Biostatistician Thomas Fleming of the University of Washington said NitroMed’s decision to end its clinical trial early diminished the quality of the company’s data. Shutting the trial down so that all patients could get BiDil may well have been the right thing to do ethically, but the resulting data made the issue a statistically “close call,” he said.
