"There was anxiety, I think, that probably made us wait a while until we were absolutely sure from our data that this was a real phenomenon, and not just a play of chance," said Dr. Jay Cohn, a University of Minnesota cardiologist involved in the study that was published in 1999.
But the study was clear: blacks responded better that whites to the drug that Cohn and his colleagues began investigating decades ago. That led to a 2001 clinical trial involving only black patients and ultimately to last month's approval to market BiDil to blacks, the first medication approved by the Food and Drug Administration for a specific racial group.
The development has raised ethics concerns about gearing medicines to a certain race but could help usher in so-called "personalized" medical treatments tailored to an individual's genetics.
The researchers and the company marketing BiDil, Lexington-based NitroMed Inc., caution against assigning too great a role to race and ethnicity in medicine. But they also say doctors shouldn't overlook those factors and they are studying BiDil further, looking to expand its use to other races. That would give NitroMed a much larger slice of the profitable U.S. market for cardiovascular drugs, which the pharmaceutical data firm IMS Health estimates at about $21 billion, including heart failure and blood pressure treatments.
NitroMed is scheduled to disclose more of its marketing plans for BiDil at an analysts' conference today.
BiDil's approval "has not only vindicated my faith in the drug, but my long-standing belief that we should do trials in targeted populations," said Cohn, a member of NitroMed's scientific advisory board who designed the blacks-only study the FDA required.
According to the U.S. Centers for Disease Control, an estimated 750,000 American blacks suffer from heart failure, which occurs when the heart is too weak to pump effectively. Half the patients die within five years of diagnosis, and middle-aged blacks are more than twice as likely than whites of the same age range to die from the condition.
BiDil is the first commercial product for NitroMed, a 22-year-old biotechnology firm specializing in research on nitric oxide, a substance key to heart health that the company is researching for other uses, including arthritis treatment.
Without any history promoting drugs, NitroMed has relied on research collaborations with other firms for much of its revenue. After NitroMed's initial public offering in November 2003, the stock initially languished below $10 a share before climbing as high as $27.99 in February of this year on expectations of BiDil's approval. The stock has recently traded around $22 to $23.
Industry analyst Jennifer Chao of Deutsche Bank North America projects BiDil will reach $192 million in sales in 2007 not bad for a company that posted a $29.7 million loss on $16.5 million in revenue last year. NitroMed has about 100 employees, plus has hired about 195 outside contractors to market BiDil.
BiDil grew out of Cohn's work in the 1970s to treat heart disease by combining medications to treat heart pain and high blood pressure. Together, the two increase nitric oxide, which is deficient in patients with failing hearts.
Dr. Manuel Worcel, NitroMed's chief medical officer, said data suggest black heart-failure patients suffer greater nitric oxide deficiency than whites. That's the apparent reason why BiDil is more effective in blacks when used in combination with other standard heart disease therapies.
The drug was first tested in a pair of 1980s clinical trials that indicated BiDil yielded benefits in combination with other drugs. Little came of the finding until researchers learned more about nitric oxide's role in heart disease. Cohn's research team began reviewing the 1980s data in 1995 to examine BiDil's effect on blacks, leading to the group's cautious publication of findings showing differing benefits depending on race.
Medco Research Inc., a now-defunct company that bought rights to BiDil from Cohn, applied to market the drug to patients regardless of race, but was rejected before Cohn published his results.
NitroMed bought rights to BiDil in 1999 and sought approval for use only in blacks. The FDA required a new trial examining the drug's effect only on black patients, which was halted ahead of schedule last fall when it found a 43 percent reduction in deaths among patients who took BiDil.
The race-specific clinical trial for BiDil generated anxiety among some members of the Association of Black Cardiologists. But ultimately, the association recruited participating doctors and urged BiDil's approval, in part because of the high incidence of heart failure among blacks.
The issue has medical ethicists questioning whether doctors might inappropriately consider race in treating patients.
Dr. Paul Root Wolpe of the University of Pennsylvania Center for Bioethics said he worries that prescribing the drug specifically for black patients may ignore the genetic variation among blacks, which can be greater than for other groups. Studies into the origins of humans have shown wider diversity among humans with roots in Africa than from other continents.
"When we say, African American' and black,' we're using a social category to try to determine genetic tendencies, and it just doesn't work very well," Wolpe said.
Critics also worry how developers of drugs like BiDil will decide which genetic traits to target.
"There certainly will be a tendency to look for the big genetic markers rather than the smaller variations, simply because it is more profitable," Wolpe said.
NitroMed suspects race is not the only factor behind BiDil's effectiveness, and is examining genetic commonalities among blacks in the study who benefited from BiDil. If that review reveals a nonracial characteristic linked to BiDil's effectiveness, further clinical studies could lead to the drug's approval for use in all races.
"It's more complicated than just genetics," Worcel said.
On the Net:
Food and Drug Administration: http://www.fda.gov
NitroMed Inc: http://www.nitromed.com