Washington Editor

The FDA approved BiDil, NitroMed Inc.'s heart failure treatment for black patients, though curiously the company was tight-lipped on news of its first approval and trading in the stock was held Friday.

"It's leaving many of us on Wall Street scratching our heads," said David Moskowitz, an analyst at Friedman, Billings, Ramsey & Co., adding that "situations like this cause investors to speculate."

NitroMed executives declined to comment to BioWorld Today and other media outlets, and earlier that morning they canceled a television interview with the CNBC cable outlet. Moskowitz told BioWorld Today that speculation arising from the company's silence has fueled takeover rumors and talk of a marketing deal, as the Lexington, Mass.-based company owns all rights to BiDil.

"But at this point, no one really knows," Moskowitz added. "We just have to wait and see."

Despite the lack of direct remarks, a prepared statement released by Anne Taylor, a professor of medicine at the University of Minnesota Medical School and the pivotal trial's lead investigator, noted that the approval would positively impact patients disproportionately affected by heart failure, which also is called end-stage cardiovascular disease. African-Americans between 45 and 64 years old are 2.5 times more likely to die prematurely from heart failure than comparably aged non-blacks, according to the Centers for Disease Control and Prevention.

"Final approval is clearly welcome news for the company," Moskowitz said. "But, more importantly, the product label appears to be very favorable, in our view."

The FDA broadly labeled the drug, a combination of isosorbide dinitrate and hydralazine hydrochloride, to improve survival, prolong time to hospitalization for heart failure and improve patient-reported functional status, as an adjunct to current standard heart failure therapy in self-identified black patients. Importantly, that indication does not limit the drug's use to particular groups of heart failure patients, as characterized by New York Heart Association guidelines.

Such an unrestrictive label was lauded by Deutsche Bank analyst Jennifer Chao, who wrote in a research note that "no mention is made to specifically exclude Class II or IV patients, which we believe was done intentionally to allow clinicians to decide which patients would be good candidates for treatment." Instead, the label simply indicates little experience in Class IV patients, those with the most severe disease.

Moskowitz, whose Arlington, Va., firm makes a market in NitroMed's stock, called the approval "as good as it gets." In addition to a lack of NYHA restrictions, he also noted that the company has a use patent that extends to 2020 for BiDil therapy in African-Americans. "It seems like really the best news that the company could have hoped for," he added.

The FDA's clearance followed the recommendation of its Cardiovascular and Renal Drugs Advisory Committee, which less than two weeks ago voted 9-0 in favor of approving BiDil. (See BioWorld Today, June 17, 2005.)

Data from the efficacy trial underlying the company's new drug application, labeled the African American Heart Failure Trial (A-HeFT), showed that self-identified black patients taking BiDil plus current standard heart failure therapies experienced a 43 percent decrease in the risk of mortality compared to placebo (p=0.012), a 39 percent reduction in the risk of first hospitalization for heart failure (p<0.001), and a statistically significant improvement at most time points in response to a quality-of-life measure, the Minnesota Living with Heart Failure Questionnaire.

Moskowitz noted that a label describing BiDil's "43 percent reduction in mortality, as well as excellent quality-of-life data, should allow the company to position the product very favorably in the market place." Along the same lines, Chao, whose New York firm makes a market in NitroMed's stock, predicted a "relatively rapid market penetration" of 4 percent into Class II patients, 18 percent into Class III and 30 percent into Class IV, leading to sales of $73 million this year.

A year ago, the study was halted early because of the significant survival benefit seen with the drug. That caused a 73 percent surge in NitroMed's stock, and those preliminary data were confirmed and reported at a scientific meeting last fall. (See BioWorld Today, July 20, 2004, and Nov. 9, 2004.)

Co-sponsored by NitroMed and the Association of Black Cardiologists, the randomized, double-blind study was the first conducted in a heart failure population in which all of the participants identified themselves as black. Its protocol was based on a hypothesis generated by a retrospective look at previous studies of the isosorbide dinitrate/hydralazine hydrochloride combination that suggested a trend for improved survival in black patients with mild to moderate heart failure.

Most of the 1,050 A-HeFT patients received a variety of other drugs in addition to BiDil or placebo, including a loop diuretic, an angiotensin converting enzyme inhibitor or an angiotensin receptor blocker, and a beta blocker. Many also received a cardiac glycoside or an aldosterone antagonist.

About 750,000 African-Americans have heart failure, which more broadly affects about 5 million Americans. BiDil, an orally administered tablet, is initially dosed three times per day, a schedule that can be maximized to two tablets three times a day based on patient tolerance. Side effects include headaches and dizziness.

The company said BiDil's exact mechanism of action remains unknown, but noted that nitrates have dilator properties that lead to the relaxation of vascular smooth muscle. Isosorbide dinitrate is a vasodilator with effects on both arteries and veins, while hydralazine is an arterial dilator.

Late last year, NitroMed publicly raised almost $80 million to build a sales team in anticipation of eventually launching the drug. Moskowitz predicted a near-term launch, with shipments beginning early next quarter. (See BioWorld Today, Dec. 9, 2004.)

Beyond its BiDil efforts, NitroMed's research is focused on developing new pharmaceuticals and improved versions of existing drugs for diseases characterized by a nitric oxide deficiency, such as cardiovascular and inflammatory conditions. Also, the company has an agreement with Boston Scientific Corp., of Natick, Mass., to develop nitric oxide-enhanced cardiovascular stents.

On Friday, NitroMed's shares (NASDAQ:NTMD) remained at $18.97 because of the hold.

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