ARCA biopharma presents data from phase 3 BEST trial of Gencaro

ARCA biopharma, Inc. has announced that data from the pivotal Phase 3 BEST trial of Gencaro (bucindolol hydrochloride) in patients with advanced chronic heart failure (CHF) was presented at the American College of Cardiology 58 th Annual Scientific Session being held March 29-31, 2009 in Orlando, Florida.

The trial results demonstrated that, in a demographically-diverse group of primarily U.S. patients with New York Heart Association (NYHA) class III and IV heart failure, Gencaro treatment resulted in a near significant overall survival benefit and statistically significant benefits in slowing progression of heart failure. These results were observed despite the premature termination of the trial, with only 92 percent of the projected primary endpoint events available and average follow-up shortened by 12 months.

Analyzed in accordance with the U.S. Food and Drug Administration (FDA)-reviewed, pre-specified statistical analysis plan, the primary endpoint of mortality was reduced in all BEST trial patients on Gencaro by 13 percent (hazard ratio (HR) 0.87; p=0.053). All eight secondary endpoints of the trial were positive and statistically significant. As pre-specified with the FDA, the composite endpoint of heart failure progression was the most important secondary endpoint, with Gencaro shown to be superior to placebo for slowing progression of heart failure (HR 0.80, p=0.00003), and for the endpoint's components of heart failure-related mortality (HR 0.85, p=0.042), heart failure-related hospital admission (HR 0.77, p=0.00002), and heart failure-related emergency room visits (HR 0.74, p=0.024).

¡°The results of the BEST trial, analyzed according to the pre-specified regulatory statistical analysis plan, are the foundation of our New Drug Application currently under review by the FDA with a PDUFA date of May 31, 2009,¡± commented Dr. Michael R. Bristow, ARCA's founder and chief science and medical officer. ¡°We believe there is a substantial need for new heart failure therapies for which response can be better predicted pharmacogenetically prior to the onset of therapy, and that Gencaro may help to address these needs.¡±

About BEST

The Beta Blocker Evaluation of Survival Trial (BEST) was a randomized, placebo-controlled trial in patients with moderate to severe heart failure (NYHA Class III or IV), testing the hypothesis that beta-blockers reduce mortality and morbidities in patients with heart failure. BEST was jointly funded by the Veteran's Administration Cooperative Clinical Studies Program (VA CCSP) and the National Heart, Lung and Blood Institute (NHLBI). As a result of the quality of data from existing studies in patients with heart failure and its tolerability, Gencaro was chosen as the beta-blocker for evaluation in this trial.

In this double-blind trial, conducted between 1995 and 1999, a total of 2,708 patients with heart failure designated as NYHA functional class III (92 percent) or IV (8 percent) and a left ventricular ejection fraction ¡Ü 35 percent were randomly assigned to treatment with either Gencaro (1,354 patients) or placebo (1,354 patients) and followed for the primary endpoint of death from any cause (all-cause mortality), and the highest ranking secondary endpoint of heart failure progression (composed of heart failure-related mortality or cardiac transplantation or heart failure-related hospitalization or heart failure-related emergency room visit). Additional secondary endpoints included: cardiovascular mortality (HR 0.84); mortality or cardiac transplantation (HR 0.86); heart failure hospitalization (HR 0.77); myocardial infarction (HR 0.53); change in need for co-therapy; quality of life (QOL); left ventricular ejection fraction (LVEF). Efficacy analyses were based on Intention to Treat (ITT).

Preliminary results from the BEST trial were reported in 2001, following early termination of the study due to loss of investigator equipoise. Pharmacogenetic results of a large (n=1040) DNA substudy indicating enhancement of therapeutic index by the use of adrenergic receptor polymorphisms have been extensively reported. However, the overall trial results analyzed according to the FDA-negotiated pre-specified statistical analysis plan (SAP) have never been reported.

The poster presented at the ACC conference is available on ARCA's website at www.arcabiopharma.com.