Medical Device Daily and Managing Editor

GAITHERSBURG, Md. – The FDA’s Cardiovascular and Renal Drugs Advisory Committee last week voted 9-0 to recommend approval of BiDil, a cardiovascular drug that will be targeted for commercialization to African-Americans.

While FDA panels are primarily tasked with focusing on the clinical benefits of therapeutics and therapeutic devices, the question of labeling – and thus marketing to a specific ethnic group – persisted throughout the day-long panel gathering to consider the recommendation for the drug made byNitroMed(Lexington, Massachusetts). The application for BiDil, a fixed combination of the generic drugs isosorbide dinitrate and hydralazine hydrochloride, was based primarily on data from a single study developed by a hypothesis that arose from two previous trials, those earlier trials failing to convince the FDA of BiDil’s value for use in the general population. However, the pilot African-American Heart Failure Trial (HeFT) demonstrated that BiDil confers a significant cardiovascular benefit among that subgroup population, improving all components of a composite primary endpoint.“Race was the strongest predictor of survival,” said Michael Sabolinski, NitroMed’s senior vice president of clinical development and regulatory affairs. And a consensus of panel members recommended that the drug’s label indicate its efficacy for African-Americans. Specifically, BiDil patients had a 43% lower risk of death, compared to those on placebo, a 39% lower risk of hospitalization for heart failure and a better quality of life. Publicity concerning the targeting of the drug to a specific racial group has raised the issue to the level of controversy in the general media, but there was not much arguing concerning the HeFT trial results.“I have to approve a drug when I think there’s evidence you can reduce mortality by 43%,” said Steven Nissen, the medical director of the cardiovascular coordinating center of theCleveland Clinic(Cleveland, Ohio) and the committee’s chairman. “As a clinician, I find the evidence more than adequate to vote for approval.” The A-HeFT data initially were reviewed last summer by a data monitoring board that recommended the company halt the trial early. When that happened, NitroMed’s stock shot upward by 73%. Those same results were confirmed and reported at a scientific meeting last fall.“BiDil represents a new heart failure treatment for African Americans,” said Clyde Yancy, a professor at theUniversity of Texas Southwestern Medical School(Dallas). Noting the disease’s disproportionate effect on that subgroup, he added that when BiDil improves outcomes for African-Americans, “this opportunity should not be missed.” The drug is thought to enhance nitric oxide, which among African-Americans has reduced bioactivity. That led Donna Christensen (Del.-Virgin Islands), a member of the Congressional Black Caucus who spoke during the committee hearing, to label the approval process “an unprecedented opportunity to significantly reduce” a leading health problem for that subpopulation. But critics also stood up during the meeting’s open public session and expressed their opposition to race-specific labeling. Some on the panel were concerned that a lack of genomic evidence was available to define race, as A-HeFT patients identified themselves as African-American without any measurable underpinning for such a classification. As a result, other critics of race-specific labeling advocated approval for the entire populace. Still, Nissen noted that “we know there are differences” between races, and he and a number of colleagues thought the drug’s efficacy was sufficiently proven when using “self-identified race as a surrogate” for genomic identifiers. NitroMed indicated that it was looking to expand the product’s target population through further studies of genetic markers and other physiological factors. The drug’s history predates NitroMed’s ownership of its rights; the company acquired its new drug application and related intellectual property in 1999. BiDil was first submitted for approval for the general population by Medco Research, a company later acquired byKing Pharmaceuticals (Bristol, Tennessee), but the FDA rejected it. The agency in 2001 encouraged NitroMed to pursue the race-specific approach used in A-HeFT. The agency did not present its review of the data during the committee meeting. Going forward, it is expected that the FDA will approve the drug, as it typically follows the advice of its advisory panels. Nevertheless, various approval scenarios all represent upside for NitroMed. With “total U.S. African-Americans with heart failure [numbering about] 745,000, we assume relatively rapid market penetration of 18% into [New York Heart Association] Class III” during BiDil’s first year of commercial launch, said Jennifer Chao, a senior analyst for biotechnology at Deutsche Bank, in a research note preceding the panel meeting. The panel recommended that BiDil’s label be indicated for Class III heart patients who already are being treated with other therapies such as ACE inhibitors and beta blockers, as was the case in most A-HeFT patients. Late last year, NitroMed raised almost $80 million in a public offering in anticipation of eventually launching the drug. To that end, the company has directed part of that funding toward building a sales team. In early after-hours trading following the Thursday meeting, the company’s stock gained 10 cents to advance to $19.51.