ARCA biopharma, Inc. (Nasdaq: ABIO) today announced that it has reached agreement with the U.S. Food and Drug Administration (FDA) regarding a Special Protocol Assessment (SPA) on the design of a clinical trial to assess the safety and efficacy of bucindolol in approximately 3,200 patients with chronic heart failure who have the genotype that appears to respond most favorably to bucindolol. Bucindolol is the Company’s investigational, pharmacologically unique, beta-blocker and mild vasodilator. An SPA is an agreement with the FDA that the proposed trial protocol design, clinical endpoints and statistical analyses are acceptable to support regulatory approval. In November 2009, the Company announced that the FDA has designated as a Fast Track development program the investigation of bucindolol for the reduction of cardiovascular mortality and cardiovascular hospitalizations in a genotype-defined heart failure population. In March 2010, ARCA was awarded a patent from the U.S. Patent and Trademark Office (USPTO) on methods of treating heart failure patients with bucindolol based on genetic testing.
“This SPA agreement with the FDA, the latest in a series of important milestones for ARCA, provides us with a clearly defined development and regulatory pathway for bucindolol in the treatment of genotype-specific heart failure patients,” said Michael R. Bristow, President and Chief Executive Officer of ARCA. “We appreciate the FDA’s approach to identifying a means by which additional bucindolol effectiveness data can be generated in a genotype-defined heart failure population. If the planned study confirms previous observations made in the BEST trial, bucindolol has the potential to become the first genetically targeted heart failure treatment for what we estimate to be the approximately 1.5 million heart failure patients with systolic dysfunction and the genotype that appears to respond most favorably to bucindolol.”
In accordance with the Company’s SPA agreement with the FDA, the bucindolol clinical trial is designed to be an international, multi-center, randomized, double-blind clinical trial with a planned enrollment of approximately 3,200 patients with chronic heart failure who have the genotype that appears to respond most favorably to bucindolol. This genotype is defined as the homozygous state for arginine (Arg/Arg) at amino acid position 389 of the beta-1 adrenergic receptor. In this genotype, all of these beta-1 receptors in the heart have high function and high affinity for norepinephrine, with a relatively large fraction of the receptors having constitutive activity, all of which are properties that the Company believes predispose the patient with this genotype to an enhanced clinical response to bucindolol. Bucindolol is unique among beta-blockers in having been shown to lower systemic norepinephrine levels and facilitate conversion of constitutively active beta-1 Arg receptors to an inactive state, pharmacologic properties that may explain bucindolol’s more favorable response in the beta-1 389 Arg/Arg genotype versus the response in another common genotype of the beta-1 receptor known as 389 Gly.