Nitromed’s BiDil Combination Therapy for Congestive Heart Failure

On November 8, 2004 Nitromed reported that the data from its Phase 3 A-HeFT trial would be published in the New England Journal of Medicine and presented at the American Heart Association’s Late Breaking Scientific Sessions. This randomized, placebo-controlled, double blind clinical trial enlisted 1050 African American patients with New York Heart Association class III or class IV congestive heart failure. Participants were treated with standard CHF regimens and BiDil, or standard CHF regimens and placebo. Due to statistically significant increased mortality in the placebo group compared to the BiDil treated group, the study was terminated early. The company reported a 43% reduction in all cause death, a 33% relative reduction in the rate of first hospitalization, and a significant improvement in the quality of life measure. NitroMed indicated that they have submitted these clinical data to the FDA and will proceed to file an amended new drug application for BiDil by the end of 2004. BioHorizon has assigned BiDil an efficacy score of 80.

BiDil is a fixed dose, combination therapy consisting of 37.5 mg of hydralazine hydrochloride and 20 mg of isosorbide dinitrate per tab taken three times daily. Although hydralazine and isosorbide dinitrate are both approved for use in several cardiovascular indications, their use together in a fixed dose format for the treatment of CHF is unique and merits an innovation score of 65. Nitric oxide is important in myocardial remodeling. BiDil may exert its therapeutic effect as both a source and preserver of nitric oxide in the heart.

Estimates of the prevalence of congestive heart failure range from 3 to 5 million Americans. We use an incidence of 400, 000 new diagnoses per annum; this translates into a burden of illness variable value of 35. Congestive heart failure results from an impairment in pump function in which the heart fails to maintain the circulation of blood adequately. In the New York Heart Association’s functional classification of CHF, class III is characterized by a marked limitation in normal physical activity. Class IV is defined by symptoms at rest or with any physical activity.

If approved, we expect significant demand/diffusion of this emerging technology. The integration of BiDil into the CHF therapeutic armamentarium will create an increase in the pharmacologic treatment cost per patient per year. BiDil will be added to existing patient specific therapeutic regimens. We have assigned the demand/diffusion variable a value of 30 and an overall BioHorizon Emerging Health Technology Impact Score of 53. If FDA approval occurs, we intend to recommend early assessment activities.

Technology Details
Target Disease / Indication: Congestive Heart Failure
Technology Classification: Drug
Body System: Cardiovascular System
Program Area: Medicine/Cardiology
Regulatory Status: Phase 3
BioHorizon Impact Score: 53/100 – Moderate