- Clinically important bradycardia is common in heart failure (HF) patients with persistent or paroxysmal atrial fibrillation (AF)
- In a Phase 2B clinical trial, the prevalence of clinically important bradycardia was statistically significantly lower for GencaroTM compared to metoprolol
The 267-patient GENETIC-AF clinical trial tested the hypothesis that pharmacogenetic inhibitory targeting of the higher function, 389 arginine (ADRB1 Arg389) variant of the beta1-adrenergic receptor (beta1-AR) by Gencaro would be more effective in preventing AF than inhibition by metoprolol succinate, a beta blocker without differentiated effects for the ADRB1 Arg389Gly polymorphism. In order to assess the prevalence and importance of bradyarrhythmias in AF-prone HF patients treated with beta blockers and to investigate potential differences between agents with different pharmacologic properties, the paper’s authors compared HRs, prevalence of bradycardia, bradycardia association with AEs, target dose attainment, and dose reductions between the second-generation beta blocker metoprolol and the fourth-generation compound Gencaro in the GENETIC-AF trial. Patients randomized to metoprolol (n = 125) or Gencaro (n = 131) entering 24-week efficacy follow-up and receiving study medication were evaluated. Bradycardia was defined as an electrocardiogram (ECG) HR <60 beats per minute (bpm) and severe bradycardia <50 bpm.
Additional analyses determined that mean HR in sinus rhythm (SR) was 62.6 ± 12.5 bpm for metoprolol and 68.3 ± 11.1 bpm for Gencaro (P < .0001), but in AF HRs were not different (87.5 bpm vs 89.7 bpm, respectively). Bradycardia episodes (HR <60 bpm) per patient for Gencaro vs metoprolol were 0.82 vs 2.08 (P < .001) with 98.9% of the episodes occurring in SR. Patients experiencing bradycardia had a 4.15-fold higher prevalence of study medication dose reduction (P <.0001) compared to patients without bradycardia. On multivariate analysis of 21 candidate bradycardia predictors including presence of a device with pacing capability, Gencaro treatment was associated with the greatest degree of prevention (Z odds ratio -4.24, P < .0001).
Dr.
About ARCA biopharma
ARCA biopharma is dedicated to developing genetically targeted therapies for cardiovascular diseases through a precision medicine approach to drug development. ARCA is developing rNAPc2 as a potential treatment for diseases caused by RNA viruses, initially focusing on COVID-19. The
Safe Harbor Statement
This press release contains "forward-looking statements" for purposes of the safe harbor provided by the Private Securities Litigation Reform Act of 1995. These statements include, but are not limited to, statements regarding the potential future development plans for Gencaro and rNAPc2, the expected features and characteristics of Gencaro and rNAPc2, including the potential for genetic variations to predict individual patient response to Gencaro, Gencaro’s potential to treat atrial fibrillation, rNAPc2’s potential to treat COVID-19, future treatment options for patients with COVID-19 or AF, and the potential for Gencaro to be the first genetically targeted AF prevention treatment. Such statements are based on management's current expectations and involve risks and uncertainties. Actual results and performance could differ materially from those projected in the forward-looking statements as a result of many factors, including, without limitation, the risks and uncertainties associated with: ARCA’s financial resources and whether they will be sufficient to meet its business objectives and operational requirements; ARCA may not be able to raise sufficient capital on acceptable terms, or at all, to continue development of rNAPc2 or Gencaro or to otherwise continue operations in the future; results of earlier clinical trials may not be confirmed in future trials; the protection and market exclusivity provided by ARCA’s intellectual property; risks related to the drug discovery and the regulatory approval process; and, the impact of competitive products and technological changes. These and other factors are identified and described in more detail in ARCA’s filings with the
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Dr. Bristow
Dr. Michael Bristow , President and CEO, ARCA biopharma, Inc.
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