ARCA biopharma, Inc. (Nasdaq:ABIO) announced that it received a Complete Response letter from the U.S. Food and Drug Administration (FDA, or the Agency) for its New Drug Application (NDA) seeking approval for GencaroTM (bucindolol hydrochloride) for the treatment of patients with chronic heart failure.

In its Complete Response letter, the FDA states that it cannot approve the NDA in its current form and specifies additional actions and information required by the Agency for approval of the Gencaro NDA. The Agency acknowledges that several substantial amendments to the NDA submitted by the Company in May 2009 were not reviewed or considered by the FDA in issuing the Complete Response letter, and that these amendments may be referenced in the Company's response to the Complete Response letter. These unreviewed submissions deal with comparative effectiveness, clinical pharmacology, some aspects of pharmacogenetic data, and toxicology/metabolism.

Among other things, the Complete Response letter states that the Company must undertake the following actions to obtain approval:

- Conduct an additional clinical efficacy trial of Gencaro in patients with heart failure;
- Conduct additional clinical pharmacology studies to address drug-drug interaction and pharmacokinetic issues; and,
- Conduct additional non-clinical studies to further characterize Gencaro metabolites.

In its Complete Response letter, FDA asserts that the BEST clinical study, which serves as the pivotal Phase III trial for the application, does not adequately demonstrate efficacy of Gencaro in reducing all-cause mortality in patients with heart failure. The letter raises concerns regarding the integrity of the BEST data based on its audit of certain clinical sites involved in the BEST trial, which may require an independent audit of additional clinical sites and other actions to verify the integrity of the data. In addition, the Complete Response letter raises concerns as to the statistical significance of some of the pharmacogenetic data relied upon by the Company to assert that individual patient response to Gencaro may be predicted by genotype.

The Company believes that data and information submitted to FDA in May 2009, which the Agency acknowledges were not reviewed before sending the Complete Response letter, may address several of the deficiencies raised by FDA and may limit the need for some of the actions specified in the letter. In particular, ARCA believes a submitted comparative effectiveness analysis demonstrates that Gencaro is as effective in reducing all-cause mortality as other β-blocker therapies, when comparable patient populations are analyzed. In addition, the May 2009 submissions to FDA included two of the requested clinical pharmacology studies, plus non-clinical data and designs of ongoing preclinical studies that were specified by FDA in the Complete Response letter. ARCA also submitted a response to some of the pharmacogenetic issues in the May amendments and plans to conduct additional analyses in response to the Agency's letter.

"The Company is reviewing the Complete Response letter and plans to discuss it with FDA as soon as possible," said Michael R. Bristow, Founder and Chief Science and Medical Officer ARCA. "We appreciate FDA's review of the NDA and will continue to work with FDA to resolve the issues raised in the Complete Response letter."

Source
ARCA Biopharma