NitroMed Inc has halted the phase III clinical trial of BiDil, its lead drug in development for the treatment of African Americans with heart failure. The trial was stopped because of the significant survival benefit seen with the drug. The action followed the unanimous recommendations of both the Data Safety and Monitoring Board (DSMB) and the Steering Committee for the trial, a company release said.
The African American Heart Failure Trial, or A-HeFT, was designed to evaluate the efficacy of BiDil, when taken daily in addition to the best current therapy. BiDil is an orally administered nitric oxide enhancing medicine, which combines isosorbide dinitrate and hydralazine. Over 1,000 patients in 170 sites across the United States were enrolled in the double blind placebo controlled trial. The Association of Black Cardiologists is a joint sponsor of the study.
Two days before the Company notified the study investigators at the 170 active clinical sites throughout the country that the trial is to be halted immediately. All patients in the A-HeFT trial will now have the opportunity to be treated with BiDil.
"The reported benefit of BiDil and the recommendation of the DSMB were so compelling that the A-HeFT Steering Committee unanimously recommended that the trial be stopped," said Dr. Anne Taylor, chairman of the A-HeFT Steering Committee and Professor of Medicine, University of Minnesota School of Medicine. The DSMB is an independent committee of experts who oversees the trial to ensure patient safety. Based on the size and consistency of the survival benefit, the committee believed it would be unethical for physicians to continue to withhold BiDil from patients taking a placebo in the study.
Although the data reviewed were preliminary and will require more robust analysis, the statistically significant survival benefit was consistent with and confirmed by the A-HeFT primary composite endpoint of mortality, first hospitalization for heart failure and quality of life. The preliminary data also indicated that serious adverse events and cardiovascular events in particular, were less frequently observed in the BiDil arm of the trial. BiDil is not yet approved for marketing by the FDA. NitroMed expects that the data from the trial will be available in the fourth quarter of 2004, the release says.
Dr. Manuel Worcel, NitroMed's chief medical officer, observed, "The survival benefit with BiDil in African American heart failure patients is consistent with the survival benefit observed in an earlier clinical study, V-HeFT I, where patients were given BiDil on top of then current therapies digoxin and diuretics. In the A-HeFT trial, patients were given BiDil in addition to the full spectrum of modern therapies which may include beta blockers, angiotensin antagonists and aldosterone inhibitors-as well as digoxin and diuretics."
"A-HeFT is the largest database ever in African-Americans with heart failure and highlights the importance of African American participation in clinical trials. The Association of Black Cardiologists is proud to be the co-sponsor of the trial," said Malcolm Taylor, chair of the Association of Black Cardiologist Heart Failure Steering Committee and member of the A-HeFT Steering Committee.
Michael D Loberg, president and CEO, NitroMed, commented, "This news indeed accelerates our timetable and, I believe, lowers our development risk to commercialization. Although the data need further analysis, NitroMed will work closely with the FDA to conclude the necessary A-HeFT data analysis and to ensure a complete and prompt filing of the data as an amendment to our previously submitted new drug application (NDA). At the same time, we intend to have the necessary commercial resources in place to support a product launch by early 2005."
A-HeFT is the first and only heart failure trial conducted in an all African American patient population, testing the effects of BiDil, when administered in addition to current heart failure therapy. The trial was expected to be completed in early 2005.