ARCA biopharma, Inc. (Nasdaq: ABIO), a biopharmaceutical company developing genetically-targeted therapies for atrial fibrillation and other cardiovascular diseases, today announced that the paper "Adrenergic Receptor Polymorphisms and Prevention of Ventricular Arrhythmias with Bucindolol in Patients with Chronic Heart Failure” was published in the journal Circulation: Arrhythmia and Electrophysiology [ http://circep.ahajournals.org/content/early/recent], a publication of the American Heart Association. The lead author on the paper is cardiologist-electrophysiologist Ryan G. Aleong of the University of Colorado Anschutz Medical Campus.
The paper analyzes the overall and pharmacogenetic effects of Gencaro (bucindolol) in reducing the incidence of serious ventricular arrhythmias. The authors based their conclusions on post-hoc analyses of clinical data from a 1040 patient DNA substudy of the Phase 3 clinical trial Beta-Blocker Evaluation of Survival Trial (BEST). The BEST Trial was sponsored by the National Heart, Lung and Blood Institute of the National Institutes of Health, and the Cooperative Studies Program of the Department of Veterans Affairs.
The paper shows that patients in the BEST Trial who received Gencaro experienced a 58% reduction in the incidence of ventricular tachycardia or fibrillation (“VT/VF”) (p = 0.00006), adjusted for the competing risk of mortality. In addition, the authors determined that Gencaro reduced the incidence of VT/VF by 74% (p = 0.00005) in patients with the beta-1 389 arginine homozygous genotype, believed to be present in about 50% of the U.S. population.
The study also analyzed the effect of two other genotypes on Gencaro’s effect on VT/VF. Based on a statistically significant test for interaction (p = 0.03), the three genotypes provide a potential method for identifying VT/VF patients for therapy. The first group is the approximately 50% of patients with the beta-1 389 arginine homozygous genotype, who had an enhanced response (event rate reduction by 74%); the next group is the approximately 40% of patients with a second genotype (beta-1 389 glycine carriers + alpha-2C 322-325 wild type homozygous) who had an intermediate response (event rate reduction by 49%) to Gencaro; and the remaining group is the approximately 10% of patients with a third genotype (beta-1 389 glycine carriers + alpha-2C 322-325 Deletion carriers), that had no response. This pharmacogenetic approach therefore defines a target population for Gencaro that has a potentially enhanced response, as well as a small subpopulation that may not benefit from therapy; the genetic identification of such "outliers" in drug response is a major goal of pharmacogenetics.