A tiny biotechnology company today will seek a crucial advisory panel endorsement for BiDil, a heart pill that could become the first drug approved for a single race.
The Food and Drug Administration panel will consider evidence from NitroMed Inc. that its pill -- a combination of two old generic drugs -- improves the life expectancy of African Americans, the only racial group included in the company’s study.
NitroMed tested the cardiac drug in blacks after the FDA rejected BiDil for general use. The Lexington, Mass., firm said the study was warranted because early evidence suggested that African Americans might benefit from the pill.
But some scientists say it’s doubtful that only African Americans will respond to BiDil.
“It is not like one group has all the bad genes,” said Neil Risch, a UC San Francisco geneticist. “They are pretty well distributed.”
The drug has stirred concern outside the world of medicine as well.
By approving a drug for one race, “you are giving biological reality to ... a cultural prejudice, and that can be dangerous,” said Gregory Dorr, an expert in the history of medicine at the University of Alabama. “The last time something was labeled for blacks, it was water coolers and restrooms.”
NitroMed said the company’s clinical trial was rooted in science. The firm’s chief executive said its drug filled an important medical need because African Americans did not respond well to existing heart treatments.
“I don’t think of BiDil as a race-based drug,” CEO Michael D. Loberg said. “We went where the data took us.”
The company has won support from such influential groups as the Assn. of Black Cardiologists, whose members were among the doctors who conducted the trial, and leaders of the Congressional Black Caucus. Donna Christensen, a Democrat from the Virgin Islands, said she would appear before the panel on behalf of NitroMed because “African Americans are dying.”
“I commend NitroMed for stepping out on a limb, knowing alarms would go off,” she said.
NitroMed’s study, published in the New England Journal of Medicine last fall, demonstrated a 43% increase in survival of African Americans who took BiDil in combination with an existing drug compared with blacks in a control group who received only that existing medicine. In addition, the study of 1,050 patients showed that those who received BiDil had fewer hospitalizations.
Among those patients was Danny Matthews, a 52-year-old former forklift operator from Plano, Texas. Before starting on BiDil two years ago, Matthews became winded going up stairs or walking from his house to his car. Now he has the energy to throw a baseball with his 10-year-old son and is looking forward to becoming well enough to return to work one day.
“I used to think I wouldn’t make it to [age] 60,” he said.
On Wednesday, the FDA staff released its analysis of BiDil in advance of the panel meeting. The staff report said BiDil could be approved as a treatment for African Americans, but raised concerns about statistical analysis of NitroMed’s data.
Much is riding on the panel vote for NitroMed, an unprofitable company with no approved products. A recommendation could clear the way to market BiDil to the 750,000 African Americans who are treated for congestive heart failure each year, a market valued at hundreds of millions of dollars. The FDA is not required to follow the advice of its panels but often does. The agency is expected to reach a decision by June 23.
Critics say BiDil is a case study in how the forces of commerce drive medicine. Jonathan Kahn, a medical ethicist at the University of Minnesota, said NitroMed proposed its study at a time when the FDA was eager to involve more African Americans in clinical trials.
NitroMed’s patent on BiDil as a treatment for African Americans expires in 2020, so the company could enjoy a long monopoly if the drug is approved only for blacks, Kahn observed. NitroMed’s patent on BiDil for general use runs out in 2007. Kahn published his analysis of the development of BiDil last year in the Yale Journal of Health Law, Policy and Ethics.
“The primary forces driving the reinvention of BiDil as an ethnic drug,” Kahn wrote, “were legal and commercial.”
Some on Wall Street speculate that NitroMed’s drug development plan may backfire. The FDA could approve BiDil for general use -- which would leave NitroMed vulnerable to competition after its first patent expired.
Even approval of the drug by the FDA for blacks only is no guarantee of success. SG Cowan & Co., an investment firm, predicted that insurers would require a high co-payment, perhaps $35 or more, for BiDil. That could drive half of all eligible patients to go to the trouble of taking the two generic drugs that make up BiDil. Co-pays on each generic would be $5 to $10, the investment firm said.
NitroMed contends that other studies have shown that race has a role in how patients respond to drugs. NitroMed says the package insert for another heart drug, Vasotec, states that drugs in its class are less effective in blacks. And NitroMed says the insert for hypertension drug Cozaar reports there is “no evidence” that the drug benefits black patients with high blood pressure.
Race is said to have a role in other drug categories. The label for Crestor, a cholesterol-lowering drug, warns that Asians could experience a side effect -- severe muscle damage -- at twice the rate of whites.
Loberg, NitroMed’s CEO, says his company does not plan to test BiDil in nonblacks. But it will look for underlying genetic traits in patients already studied, in an effort to identify patients of any race who may benefit.
UC San Francisco geneticist Risch questioned that approach, saying that race is a socially and genetically complex question and that all sorts of external factors -- such as life experience and socioeconomic status -- influence disease pathology.
“Saying the drug works in people who self-identify as African American doesn’t prove the reason is genetic,” he said.
Clinical trials testing BiDil in other racial groups are needed, Risch added. “I don’t think there is any substitute for studying different groups.”
The research that led to BiDil began in the 1970s, when Jay N. Cohn, a cardiologist with the Veterans Administration, began experimenting with two generic drugs, isosobide dinitrate and hydralazine.
Isosobide increases levels of nitric oxide, a chemical that relaxes blood vessels. Hydralazine prevents nitric oxide from breaking down. Cohn had a hunch the combination might benefit cardiac patients, though neither drug was approved for heart failure.
Cohn organized two clinical trials that tested the drug combination in Veterans Administration patients, obtained a patent on the treatment regimen and licensed it to what is now King Pharmaceuticals Inc. King used the patent to make BiDil, a single pill containing the two generic drugs.
In 1987, the FDA refused to approve BiDil for general use. Although one clinical trial indicated that BiDil had a favorable effect, the second trial demonstrated that the drug combination was inferior to so-called ACE inhibitors, another kind of drug used to treat heart failure. In addition, an FDA panel found statistical problems with the studies. King returned the license to Cohn.
Cohn, now with the University of Minnesota, said a close look at the data showed that African Americans strongly benefited from BiDil. Cohn said no large drug company was interested in BiDil, but NitroMed was.
Cohn, who will receive a royalty on sales of BiDil, says he believes it probably will be effective in patients who aren’t black. In fact, he says, he prescribes the generic drugs that make up BiDil for the 25% of his white patients who don’t do well on other drugs.
“I actually think everybody should be using it,” Cohn said.