NitroMed┬« is an emerging pharmaceutical company that was founded to explore and leverage the therapeutic benefits of nitric oxide, which is thought to play a role in a variety of biological processes. Its first commercialized medicine is BiDil┬« (isosorbide dinitrate/hydralazine hydrochloride), a fixed-dosed combination tablet available in the US for the adjunct treatment of heart failure (HF) in self-identified black patients.
The companyÔÇÖs leading drug, BiDil, was approved by the US Food and Drug Administration (FDA) on June 23, 2005. BiDil is indicated for the treatment of HF as an adjunct to current standard therapy, in self-identified black patients, to improve survival, prolong time to hospitalization for HF, and improve patient-reported functional status. There is little experience in patients with NewYork Heart Association (NYHA) class IV HF (see full indication below). NitroMed is directly marketing BiDil to HF specialists and hospitals through a team of cardiovascular business managers.
The FDA approval of BiDil was based, primarily, on the efficacy data from the companyÔÇÖs landmark African-American Heart Failure Trial (A-HeFT). A-HeFT, co-sponsored by NitroMed and the Association of Black Cardiologists, Inc., was the first study conducted in a HF population in which all of the participants identified themselves as black. This phase III trial commenced in May 2001, and evaluated the effects of BiDil in self-identified black patients, when taken in addition to current standard HF therapies. After a unanimous recommendation from the independent Data and Safety Monitoring Board and Steering Committee in July 2004, A-HeFT was halted early, due to a significant survival benefit seen with BiDil, compared with current standard therapy alone.
In A-HeFT, most patients received (in addition to BiDil or placebo) a loop diuretic, an angiotensin converting enzyme (ACE) inhibitor, or an angiotensin-2 receptor blocker (ARB), and a beta-blocker, and many also received a cardiac glycoside, or an aldosterone antagonist. Patients taking BiDil in addition to current standard HF therapies experienced a significant 43% decrease in the risk of mortality (p=0.012; absolute mortality rate: BiDil 6.2% versus placebo 10.2%), a 39% reduction in the risk of first hospitalization for HF (p<0.001; absolute first hospitalization rate: BiDil 16.4% versus placebo 24.4%) and a statistically significant improvement in patient reported functional status versus patients taking placebo. The results from A-HeFT were presented at the American Heart Association (AHA) 2004 Scientific Sessions and were published in the November 11, 2004 issue of the New England Journal of Medicine.