ARCA biopharma has announced plans to investigate Gencaro (bucindolol hydrochloride) as a genetically-targeted therapy in a pivotal Phase III clinical trial for atrial fibrillation (AF) in patients with a certain type of heart failure (HF).
Gencaro is an investigational, beta-blocker and mild vasodilator. The company identified common genetic variations that could potentially predict patients’ individual response to the therapeutic, allowing its use as a genetically-targeted AF prevention treatment.
The double-blind, active-controlled, multi-centre Phase III trial, called PRECISION-AF, will compare Gencaro’s ability to prevent AF recurrence or all-cause mortality (ACM) with that of Toprol-XL (metoprolol succinate).
The international trial’s target population is HF patients with mid-range ejection fraction (HFmrEF), which is said to currently lack approved therapies in the US.
It will enrol approximately 400 subjects with HFmrEF, a recent AF event and the genotype which responds most favourably to Gencaro.
The trial’s primary endpoint will be the time to the first event of atrial fibrillation / atrial flutter (AF/AFL) or ACM during the 26-week follow-up period.
ARCA reached a Special Protocol Assessment (SPA) agreement with the US Food and Drug Administration (FDA) on the design of the trial.
This agreement says that the protocol design, clinical endpoints, trial population and statistical analyses of the Phase III trial adequately address objectives.
If met, these objectives would support a regulatory filing seeking Gencaro approval for the prevention of AF recurrence in a genotype-defined HF population.
ARCA biopharma CEO Michael Bristow said: “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 III development of Gencaro in a genotype-specific heart failure population that currently has no FDA approved drug therapy.”
In a previous Phase II GENETIC-AF trial, the drug demonstrated a 58% treatment benefit in minimising AF recurrence in the HFmrEF population compared to Toprol-XL.
The Phase III PRECISION-AF trial is expected to be initiated in the fourth quarter of this year.