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$ABIO Clinical Trials



SUMMARY OF TRIAL
GENETIC-AF
A Genotype-Directed Comparative Effectiveness Trial of Bucindolol and Toprol-XL for Prevention of Symptomatic Atrial Fibrillation/Atrial Flutter in Patients With Heart Failure

GENETIC-AF was a Phase 2B multi-center, randomized, double-blind, clinical superiority trial comparing the safety and efficacy of Gencaro™ against an active comparator, the beta-blocker Toprol XL (metoprolol succinate) for the treatment and prevention of recurrent atrial fibrillation or flutter (AF/AFL) in heart failure patients with reduced left ventricular ejection fraction (HFrEF). Eligible patients had HFrEF, a history of paroxysmal AF (episodes lasting 7 days or less) or persistent AF (episodes lasting more than 7 days and less than 1 year) in the past 6 months, and the beta-1 389 arginine homozygous genotype that we believe responds most favorably to Gencaro™. A subset of patients in the trial also underwent continuous heart rhythm monitoring to assess AF burden, which is defined as the amount of time per day that a patient experiences AF. These data were collected via newly or previously implanted Medtronic devices capable of assessing AF burden (for example, implantable loop recorders, pacemakers, cardioverter-defibrillators, or cardiac resynchronization therapy devices). Topline results of GENETIC-AF were reported on February 26, 2018.

GENCARO™

AN UNMET NEED
Our lead product candidate, Gencaro™ (bucindolol hydrochloride), is a pharmacologically unique beta-blocker and mild vasodilator that we are evaluating in a clinical trial for the treatment and prevention of recurrent atrial fibrillation, or AF, in patients with heart failure with reduced left ventricular ejection fraction, or HFREF.

Beta-blockers, a well characterized class of drugs, target cardiac myocytes to reduce adverse beta1- adrenergic signaling that causes cardiac chamber remodeling. We believe Gencaro’s mechanism of action (MOA) is unique among beta-blockers due to its sympatholytic (norepinephrine lowering) and inverse agonism (inactivation of constitutively active receptors) properties.

We have identified common genetic variations in receptors in the cardiovascular system that we believe interact with Gencaro’s pharmacology and may predict patient response to the drug. The genotype which responds most favorably to Gencaro, beta-1 389 arginine homozygous, is present in approximately 50% of the U.S. population.

The approved therapies for the treatment or prevention AF have certain disadvantages in heart failure patients, such as toxic or cardiovascular adverse effects, and most of the approved drugs for AF are contraindicated or have warnings in their prescribing information for such patients. We believe there is an unmet medical need for new AF treatments that have fewer side effects than currently available therapies and are more effective, particularly in heart failure patients.

GENCARO™ HEART FAILURE DEVELOPMENT PROGRAM SUMMARY
The active pharmaceutical ingredient in Gencaro™, bucindolol hydrochloride, has been tested clinically in approximately 4,500 patients, including over 3,250 patients in eight clinical trials in HFREF patients. Gencaro™ was most recently evaluated in the GENETIC-AF clinical trial as a potential treatment for atrial fibrillation in HFREF patients.