ARCA biopharma, Inc. (NASDAQ:ABIO), a biopharmaceutical company applying a precision medicine approach to developing genetically targeted therapies for cardiovascular diseases, today announced that clinical data evaluating Gencaro™ (bucindolol hydrochloride) as a potential treatment for atrial fibrillation (AF) in patients with heart failure (HF) was presented at the 2020 Heart Rhythm Scientific Sessions, the annual scientific conference of the Heart Rhythm Society (HRS). While the in-person meeting was cancelled due to the continued global escalation of COVID-19, HRS has provided author presentations virtually through its online learning platform Heart Rhythm 365 and all abstracts will be published in a supplement to the May edition of the Heart Rhythm Journal.
The data come from a Phase 2 clinical trial, GENETIC-AF, that enrolled 267 HF patients with a current or recent history of paroxysmal or persistent AF and the ADRB1 Arg389Arg genotype. Patients were randomized to bucindolol or the active comparator, metoprolol succinate, and were followed for approximately 24 weeks.
“Pharmacogenomic Guided Beta-Blocker Therapy with Bucindolol Reduces Atrial Fibrillation Burden Compared to Metoprolol Succinate: The GENETIC-AF Trial,” authored by Jonathon P. Piccini et al, presented data from the device substudy of the GENETIC-AF trial. A total of 69 HF patients underwent continuous heart rhythm monitoring via implanted cardiac devices to evaluate the total time spent in AF during 24 weeks of follow-up, also known as cumulative AF burden. The paper’s authors concluded that:
- Bucindolol decreased cumulative AF burden by 26% (p < 0.001) compared to active control.
- Treatment effect estimates for cumulative AF burden were consistent with time to first AF event analyses.
- Cumulative AF burden evaluates more information than time to first event methods, providing greater power to detect clinically meaningful differences between groups with limited sample size.
“Impact of Pharmacogenetic-guided Bucindolol versus Metoprolol Succinate on the Overall Burden of Clinical Events in Patients with AF and Heart Failure: The GENETIC-AF Trial,” authored by Jeff S. Healey et al, presented data on the frequency of AF rhythm interventions (i.e., electrical cardioversions, ablations, and Class 3 antiarrhythmic drug use) and cardiovascular (CV) adverse events in the GENETIC-AF trial. The paper’s authors found that:
- Bucindolol decreased a composite endpoint of AF interventions and CV adverse events
by 30% (p = 0.008) compared to active control.
- Bucindolol decreased AF interventions by 33% (p = 0.009) compared to active control.
- Significant and numerically greater results were observed (46% and 51%, respectively)
in a subgroup previously identified by precision therapeutic phenotyping (PTP cohort).
- Similar significant results were observed (55% and 58%, respectively) for a subgroup of the PTP cohort with baseline LVEF values of 40% to 55%.
“Bucindolol is Associated with a Lower Incidence of Dose Limiting Bradycardia in Heart Failure Patients with Atrial Fibrillation: The GENETIC-AF Trial,” authored by William T. Abraham et al, reviewed drug dosing and safety data for the GENETIC-AF trial. The paper’s authors found that:
- Bucindolol was associated with a 55% (p < 0.001) lower incidence of bradycardia compared to active control.
- Bradycardia was associated with a 4-fold increase in study drug dose reductions.
- Differences in study drug dosing were primarily observed in patients with heart rates less than 60 beats per minute, which was much more common in the metoprolol group (p < 0.0001).
- Fewer bradycardia adverse events in the bucindolol vs. metoprolol groups (5 vs. 20 events, p = 0.003).
- Bradycardia may limit dosing of conventional beta-blockers in HF patients with AF, which would be expected to compromise effectiveness for reducing HF clinical events.