Gencaro™ Potential Efficacy in Preventing Atrial Fibrillation Paper Published in JACC: Heart Failure

  Gencaro™ Potential Efficacy in Preventing Atrial Fibrillation Paper
  Published in JACC: Heart Failure

    Pharmacogenetic Enhancement of Effectiveness for Prevention of Atrial
   Fibrillation in Patients with Heart Failure and Reduced Left Ventricular
                              Ejection Fraction

Business Wire

BROOMFIELD, Colo. -- June 6, 2013

ARCA biopharma, Inc. (Nasdaq: ABIO), a biopharmaceutical company developing
genetically-targeted therapies for cardiovascular diseases, today announced
that the paper “Prevention of Atrial Fibrillation by Bucindolol is Dependent
on the Beta-1 389 Arg/Gly Adrenergic Receptor Polymorphism” was published in
the journal JACC: Heart Failure
[http://heartfailure.onlinejacc.org/article.aspx?articleid=1691088], a
publication of the American College of Cardiology. The lead author on the
paper is cardiologist-electrophysiologist Ryan G. Aleong of the University of
Colorado, Anschutz Medical Campus and the senior author on the paper is Dr.
Michael Bristow, the Company’s Chief Executive Officer.

The authors investigated the potential efficacy of the developmental drug
Gencaro™ (bucindolol hydrochloride) in reducing the incidence of new onset
atrial fibrillation (“AF”) in patients with advanced heart failure with
reduced left ventricular ejection fraction (“HFREF”), and the potential impact
of certain cardiac adrenergic receptor (“AR”) genotypes on this efficacy. The
study was based on a post-hoc analysis of the Phase 3 clinical trial of 2,708
HFREF patients known as the Beta-Blocker Evaluation of Survival Trial (the
“BEST Trial”), including a DNA substudy of 1,040 patients in the Trial. The
study analyzed Gencaro’s potential efficacy in reducing the risk of developing
new onset AF in the 2,392 patients who entered the Trial not in AF, including
the 925 patients in the DNA substudy who entered the Trial not in AF.

The study found that in the overall study population, patients who had
received Gencaro had a 41% lower risk of new onset AF (p = 0.0004) compared to
patients who received a placebo (this compared with a 43% lower risk of new
onset AF (p = 0.014) from Gencaro treatment compared to placebo in all
genotypes in the DNA substudy). However, the risk of new onset AF was reduced
by 74% (p = 0.0003) compared to placebo in those patients in the DNA substudy
who received Gencaro and who possessed the beta-1 AR position 389 arginine
homozygous (“beta-1 389 arginine homozygous”) genotype.

The Company estimates that the beta-1 389 arginine homozygous genotype is
present in about 50% of the general U.S. population, and was present in about
47% of the patients in the BEST DNA substudy. The BEST Trial was sponsored by
the National Heart, Lung and Blood Institute of the National Institutes of
Health, and the Cooperative Studies Program of the Department of Veterans
Affairs.

The authors propose that the greater reduction in AF seen by patients with the
beta-1 389 arginine homozygous genotype who received Gencaro may be due to the
interaction of Gencaro’s pharmacology with the pathophysiology of AF, where,
according to other research, both acute and chronic beta-1 AR stimulation may
be important contributors. The paper notes that the currently approved
anti-arrhythmic drugs are subject to multiple adverse effects in HFREF
patients, and have not been associated with improved cardiovascular outcomes
in those patients. The paper also notes that approved beta-blockers exhibit
only modest efficacy for reducing new onset AF in HFREF patients, and none are
currently approved for this indication.

Jonathan Piccini, MD, Director of the Cardiac Electrophysiology Clinical
Trials Program at Duke University Medical Center, said, “AF is a common
arrhythmia that is best avoided, particularly in left ventricular (“LV”)
dysfunction-heart failure patients where it can worsen the clinical syndrome
and/or appear to reduce the efficacy of some of the most effective heart
failure treatments, such as conventional beta-blockers. Although catheter
ablation may be effective for treating/preventing AF episodes, medical therapy
still needs to be tried first and is used on AF recurrence. The current
problem with drug therapy for preventing AF in an LV dysfunction-heart failure
patient is that the FDA-approved anti-arrhythmic agents have adverse safety
profiles, due to pro-arrhythmia and/or myocardial depression. Based on the
data of Aleong et al, Gencaro may potentially not have these adverse effects.
In addition, compared to standard anti-arrhythmic agents or conventional
beta-blockers, Gencaro has the potential for higher efficacy in preventing AF
in patients with the beta-1 389 arginine homozygous genotype.”

Stuart Connolly, MD, Director of the Division of Cardiology at McMaster
University in Hamilton, Ontario, commented, “The paper by Aleong et al
suggests that pharmacogenetically targeted Gencaro may have a major effect
(>70% reduction in event rate) on prevention of AF in an advanced
LV-dysfunction heart failure population with the beta-1 389 arginine
homozygous genotype. In addition, in this same population and genotype from
the BEST Trial, the authors have previously published results indicating
potentially substantial beneficial effects on heart failure endpoints and
potential prevention of ventricular tachycardia or ventricular fibrillation,
suggesting that Gencaro may not be accompanied by the same sort of safety
issues that plague ion channel blocking anti-arrhythmic agents. Therefore, in
the estimated approximately 50% of LV dysfunction-heart failure patients who
have the beta-1 389 arginine homozygous genotype, Gencaro has the potential to
be a promising treatment for preventing AF in at-risk patients.”

Michael Bristow, MD, PhD, cardiologist/clinical pharmacologist, also
commented, “We believe the 74% reduction in risk of new onset AF in the beta-1
389 arginine homozygous genotype suggests that Gencaro warrants further study
in HFREF patients at risk for AF. Previous studies of the BEST Trial data have
suggested that Gencaro may provide multiple benefits for such patients,
including AF prevention, rate control for patients with persistent AF, and
improved outcomes for both those patients that are able to maintain sinus
rhythm and those that do not. We plan to assess Gencaro’s potential efficacy
in the Phase 2b/3 GENETIC-AF clinical trial, which we plan to conduct in
beta-1 389 arginine homozygous HFREF patients, post electrical cardioversion
for persistent AF.”

ARCA plans to evaluate Gencaro’s efficacy in preventing AF in patients with
the beta-1 389 arginine genotype in a 620 patient, Phase 2b/3 clinical trial,
known as GENETIC-AF, in which Gencaro will be compared to the beta-blocker
metoprolol CR/XL. ARCA has created an adaptive design for GENETIC-AF, in which
the trial is planned to be initiated as a Phase 2b study in approximately 200
HFREF patients with the beta-1 389 arginine genotype. Depending on the results
of the Phase 2B portion, the trial could then be expanded to a Phase 3 study
by enrolling an estimated additional 420 patients. ARCA and Medtronic, Inc., a
leader in medical technologies to improve the treatment of chronic diseases
including cardiac rhythm disorders, have agreed to collaborate on the Phase 2b
portion of GENETIC-AF trial that will include continuous monitoring of the
cardiac rhythms in all 200 patients enrolled in this Phase.

AF is considered an epidemic cardiovascular disease with an estimated
prevalence of at least 2.7 million Americans in 2010. The approved therapies
for the treatment or prevention of AF have certain disadvantages in HFREF
patients, such as toxic or cardiovascular adverse effects, and most of the
approved drugs for AF are contra indicated or have warnings in their
prescribing information for such patients. ARCA believes 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 HFREF patients.

About ARCA biopharma

ARCA biopharma is dedicated to developing genetically-targeted therapies for
cardiovascular diseases. The Company's lead product candidate, Gencaro™
(bucindolol hydrochloride), is an investigational, pharmacologically unique
beta-blocker and mild vasodilator being developed for atrial fibrillation.
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 atrial fibrillation prevention treatment. For more
information please visit www.arcabiopharma.com.

Safe Harbor Statement

This press release and the associated presentation may contain
"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 ability of genetic variations
to predict individual patient response to Gencaro, Gencaro’s potential to
treat atrial fibrillation, Gencaro’s potential to treat ventricular
tachycardia or ventricular fibrillation, and the potential for Gencaro to be
the first genetically-targeted atrial fibrillation 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:
the Company's financial resources and whether they will be sufficient to meet
the Company's business objectives and operational requirements; results of
earlier clinical trials may not be confirmed in future trials, the protection
and market exclusivity provided by the Company’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
SEC, including without limitation the Company’s annual report on Form 10-K for
the year ended December 31, 2012, the Company’s Registration Statement on Form
S-1 (Registration No. 333-187508), and subsequent filings. The Company
disclaims any intent or obligation to update these forward-looking statements.

Contact:

ARCA biopharma, Inc.
Christopher D. Ozeroff, 720-940-2100
Senior Vice President and General Counsel
 
Press spacebar to pause and continue. Press esc to stop.