Data on Gencaro Impact on Prevention of Bradycardia Published in Heart Rhythm O2
05 January 2022 - 12:30AM
ARCA biopharma, Inc. (Nasdaq: ABIO), a biopharmaceutical company
applying a precision medicine approach to developing genetically
targeted therapies for cardiovascular diseases, today announced
that the paper entitled “Dose Limiting, Adverse Event Associated
Bradycardia with β-blocker Treatment of Atrial Fibrillation in the
GENETIC-AF Trial” (William Abraham, et al) has been published in
Heart Rhythm O2, a publication of the Hearth Rhythm Society. The
paper details an analysis that examined the prevalence of
bradycardia and its association with adverse events (AEs) and
failure to achieve target dose in the GENETIC-AF Phase 2b clinical
trial. In the genetically defined population of GENETIC-AF (all
ADRB1 Arg389Arg genotype), the prevalence of clinically important
bradycardia was lower for Gencaro compared to metoprolol, with an
incidence of heart rate (HR) <50 beats/min of 0.24
episodes/patient per 6 months compared to 0.57 episodes/patient per
6 months for metoprolol succinate (P < .0001). This
translated to less dose reduction or limitation in the Gencaro
group, with 75% of Gencaro subjects achieving target dose compared
to 62% for metoprolol (P <0.0001) and 13 bradycardia adverse
events in the metoprolol group compared to one for Gencaro (P =
0.001).
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).
William T. Abraham, MD, FACP, FACC, College of
Medicine Distinguished Professor, Division of Cardiovascular
Medicine at The Ohio State University Wexner Medical Center and
first author of the paper stated, "Heart failure patients with
atrial fibrillation often have conduction system disorders, which
may be worsened by beta-blocker therapy. Bradycardia and its
necessary management by dose reduction or limitation may compromise
efficacy for treating both AF and HF. In this analysis of the
on-treatment cohort of GENETIC-AF, patients receiving metoprolol
succinate compared to Gencaro experienced more bradycardia, more
bradycardia-associated AEs, and more associated dose reductions
resulting in an overall lower achievement of target dose. As
clinical investigators, we are eager to take what we've learned in
GENETIC-AF and apply it to the planned Phase 3 PRECISION-AF
trial."
Dr. Michael Bristow, ARCA’s President and Chief
Executive Officer, commented, “Atrial fibrillation is common in
patients with heart failure. This intersection is clinically
important, as the presence of each disorder worsens the prognosis
of the other, complicates disease management, and is associated
with worse outcomes, including greater rates of heart failure
hospitalization, stroke and death. The observations from this
recent analysis reinforce the rationale for the development of
atrial fibrillation therapeutic approaches that maintain sinus
rhythm in heart failure patients, and also reverse or prevent the
progression of heart failure, which is what we plan to evaluate in
the upcoming Phase 3 PRECISION-AF trial.”
About ARCA biopharmaARCA
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 U.S. FDA has granted Fast Track designation to the
rNAPc2 development program, currently in Phase 2 clinical testing.
ARCA is also developing GencaroTM (bucindolol hydrochloride), an
investigational, pharmacologically unique beta-blocker and mild
vasodilator, as a potential treatment for atrial fibrillation in
heart failure patients. ARCA has identified common genetic
variations that it believes predict individual patient response to
Gencaro, giving it the potential to be the first genetically
targeted AF prevention treatment. The U.S. FDA has granted the
Gencaro development program Fast Track designation and a Special
Protocol Assessment (SPA) agreement. For more information, please
visit www.arcabio.com or follow the Company on LinkedIn.
Safe Harbor StatementThis 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 Securities and Exchange Commission, including
without limitation ARCA’s annual report on Form 10-K for the year
ended December 31, 2020, and subsequent filings. ARCA
disclaims any intent or obligation to update these forward-looking
statements.
Investor & Media
Contact:Derek Cole720.940.2163derek.cole@arcabio.com
A photo accompanying this announcement is available at
https://www.globenewswire.com/NewsRoom/AttachmentNg/af496e97-20da-420a-bf93-e51b3a3ed740.
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