Washington Editor

GAITHERSBURG, Md. - The FDA's Cardiovascular and Renal Drugs Advisory Committee voted unanimously to recommend approval of NitroMed Inc.'s BiDil, though questions on labeling for the cardiovascular drug persisted throughout the daylong gathering as a result of a typically touchy topic - race.

That's because the Lexington, Mass.-based company is seeking clearance to market the product, a fixed combination of the generic drugs isosorbide dinitrate and hydralazine hydrochloride, for African-Americans. The application primarily was based on data from a single study developed by a hypothesis that arose from two previous trials - that BiDil confers a significant cardiovascular benefit among that population subgroup. The pivotal study, called A-HeFT (the African-American Heart Failure Trial), found that BiDil, indeed, improved 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 among African-Americans. Specifically, BiDil patients had a 43 percent lower risk of death compared to those on placebo, a 39 percent lower risk of hospitalization for heart failure and a better quality of life.

"I have to approve a drug when I think there's evidence you can reduce mortality by 43 percent," said Steven Nissen, the medical director of the Cleveland Clinic's cardiovascular coordinating center 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 percent. Those same results were confirmed and reported at a scientific meeting last fall. (See BioWorld Today, July 20, 2004, and Nov. 9, 2004.)

"BiDil represents a new heart failure treatment for African-Americans," said Clyde Yancy, a professor at the University of Texas Southwestern Medical School. 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 Rep. Donna Christensen (D-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 proved 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 first was submitted for approval for the general population by Medco Research, a company later acquired by King Pharmaceuticals Inc., of Bristol, Tenn., but the FDA rejected it.

The agency in 2001 encouraged NitroMed to pursue the race-specific study, A-HeFT. Going forward at this point, it is expected that the FDA will approve the drug, as it typically follows the advice of its advisory panels. The agency did not present its review of the data during the committee meeting.

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 percent 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 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. (See BioWorld Today, Dec. 9, 2004.)

On Thursday, its shares (NASDAQ:NTMD) were not traded as the meeting proceeded. In early after-hours trading, the stock gained 10 cents to advance to $19.51.