Tuesday February 26, 2019 0 comments
WESTMINSTER -- ARCA biopharma, Inc. (Nasdaq: ABIO), a biopharmaceutical company applying a precision medicine approach to developing genetically-targeted therapies for cardiovascular diseases, announced it has reached agreement with the U.S. Food and Drug Administration (FDA) regarding a Special Protocol Assessment (SPA) on the design of a pivotal Phase 3 clinical trial, PRECISION-AF, to assess the safety and efficacy of Gencaro (bucindolol hydrochloride) as a genetically-targeted treatment for atrial fibrillation (AF) in patients with a specific type of heart failure (HF).
The target population for the planned Phase 3 clinical trial, partially identified by precision therapeutic phenotyping, currently has no FDA approved drug therapies. This SPA provides agreement that the Phase 3 protocol design, clinical endpoints, trial population and statistical analyses adequately address objectives that, if met, would support a regulatory submission seeking approval of Gencaro for the prevention of AF recurrence in a genotype-defined HF population.
If PRECISION-AF is successful and Gencaro gains regulatory approval, ARCA said it has the potential to be unique in several aspects, including:
- The first genetically-targeted cardiovascular therapy;
- The only drug therapy indicated in HF patients with mid-range ejection fraction (HFmrEF); and,
- The only drug therapy for AF approved against an active comparator.
The SPA process is designed to facilitate review and approval of drugs by allowing FDA to evaluate the proposed design and size of specific clinical trials that are intended to form the primary demonstration of a drug product’s efficacy and safety.
FDA ultimately assesses whether the protocol design and planned analysis of the trial are acceptable to support regulatory approval of the product candidate for the indication studied.
An SPA agreement can potentially reduce the regulatory risk of bringing a drug to market.
"Consistent with our mission to develop precision therapies on a pharmacogenetic platform, this SPA agreement with the FDA provides a clearly defined regulatory pathway for the Phase 3 development of Gencaro in a genotype-specific heart failure population that currently has no FDA approved drug therapy," said Michael R. Bristow, ARCA CEO.
"If the previous foundational therapeutic observations in the GENETIC-AF and BEST trials are confirmed in PRECISION-AF, we believe Gencaro could potentially provide a new standard of treatment for AF prevention for the estimated 2.5 million HFmrEF patients in the major markets in U.S., Europe and Japan."
In accordance with the company’s SPA agreement with FDA, PRECISION-AF is designed as a single, adequate and well-controlled Phase 3 clinical trial that may be sufficient to support a New Drug Application (NDA) submission for an AF indication if the objectives of the trial are achieved consistent with the requirements of the SPA.
The trial is designed as a double-blind, active-controlled, multicenter, international study comparing Gencaro with Toprol-XL (metoprolol succinate) for the prevention of AF recurrence or all-cause mortality (ACM) in HFmrEF patients.
HFmrEF is defined as HF with a left ventricular ejection fraction (LVEF) ≥ 40% and < 50%, which constituted approximately half of the enrolled population in the Phase 2 GENETIC-AF trial.
PRECISION-AF is designed to enroll approximately 400 patients who have: HFmrEF, a recent AF event, and the genotype that responds most favorably to Gencaro. The primary endpoint of the trial will be time to first event of atrial fibrillation/atrial flutter (AF/AFL) or ACM during the 26-week Follow-Up Period.
In the recently completed GENETIC-AF trial, Gencaro showed a 58% treatment benefit compared to Toprol-XL in reducing AF recurrence in the HFmrEF population targeted for Phase 3 (hazard ratio = 0.42; 95% CI: 0.21, 0.86; p = 0.017). With 400 patients (200 per arm) the trial will have 90% power at a p-value of 0.01 to detect a 45% treatment benefit for Gencaro compared to Toprol-XL.
Subject to securing additional financing, ARCA anticipates initiating PRECISION-AF in the fourth quarter of 2019.