ARCA biopharma has received a complete response letter from the FDA, rejecting its new drug application (NDA) that was seeking approval for Gencaro (bucindolol hydrochloride) for the treatment of patients with chronic heart failure.
In its letter, the agency said 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.
However, the agency acknowledges that several substantial amendments to the NDA submitted by ARCA in May were not reviewed or considered by the FDA in issuing the letter, and that these amendments may be referenced in ARCA's response to the letter. The unreviewed submissions deal with comparative effectiveness, clinical pharmacology, some aspects of pharmacogenetic data and toxicology/metabolism, according to the Broomfield, Colo.-based ARCA.
Among other things, the FDA said that the company must undertake the following actions to obtain approval:
- Conduct an additional clinical efficacy trial of Gencaro in heart failure patients;
- 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 letter, the FDA asserted that the BEST clinical study, which served 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 also raised concerns regarding the integrity of the BEST data based on the FDA's 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 letter raised 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.