GencaroTM Effect on Reducing Ventricular Arrhythmias Paper Published in Circulation: Arrhythmia and Electrophysiology

  GencaroTM Effect on Reducing Ventricular Arrhythmias Paper Published in
  Circulation: Arrhythmia and Electrophysiology

Business Wire

BROOMFIELD, Colo. -- January 3, 2013

ARCA biopharma, Inc. (Nasdaq: ABIO), a biopharmaceutical company developing
genetically-targeted therapies for atrial fibrillation and other
cardiovascular diseases, today announced that the paper "Adrenergic Receptor
Polymorphisms and Prevention of Ventricular Arrhythmias with Bucindolol in
Patients with Chronic Heart Failure” was published in the journal Circulation:
Arrhythmia and Electrophysiology
[http://circep.ahajournals.org/content/early/recent], a publication of the
American Heart Association. The lead author on the paper is
cardiologist-electrophysiologist Ryan G. Aleong of the University of Colorado
Anschutz Medical Campus.

The paper analyzes the overall and pharmacogenetic effects of Gencaro
(bucindolol) in reducing the incidence of serious ventricular arrhythmias. The
authors based their conclusions on post-hoc analyses of clinical data from a
1040 patient DNA substudy of the Phase 3 clinical trial Beta-Blocker
Evaluation of Survival Trial (BEST). 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 paper shows that patients in the BEST Trial who received Gencaro
experienced a 58% reduction in the incidence of ventricular tachycardia or
fibrillation (“VT/VF”) (p = 0.00006), adjusted for the competing risk of
mortality. In addition, the authors determined that Gencaro reduced the
incidence of VT/VF by 74% (p = 0.00005) in patients with the beta-1 389
arginine homozygous genotype, believed to be present in about 50% of the U.S.
population.

The study also analyzed the effect of two other genotypes on Gencaro’s effect
on VT/VF. Based on a statistically significant test for interaction (p =
0.03), the three genotypes provide a potential method for identifying VT/VF
patients for therapy. The first group is the approximately 50% of patients
with the beta-1 389 arginine homozygous genotype, who had an enhanced response
(event rate reduction by 74%); the next group is the approximately 40% of
patients with a second genotype (beta-1 389 glycine carriers + alpha-2C
322-325 wild type homozygous) who had an intermediate response (event rate
reduction by 49%) to Gencaro; and the remaining group is the approximately 10%
of patients with a third genotype (beta-1 389 glycine carriers + alpha-2C
322-325 Deletion carriers), that had no response. This pharmacogenetic
approach therefore defines a target population for Gencaro that has a
potentially enhanced response, as well as a small subpopulation that may not
benefit from therapy; the genetic identification of such "outliers" in drug
response is a major goal of pharmacogenetics.

Stuart Connolly, M.D., of McMaster University, an
electrophysiologist-cardiologist, commented: "I believe that beta-blockers
have only modest effects on prevention of serious ventricular arrhythmias, but
in the Aleong et al study, patients with the higher activity beta-1 receptor
genetic variant (389 arginine homozygous) had a significant (by 74%, p =
0.00005) and genotype specific reduction in the risk of ventricular
tachycardia or fibrillation. This suggests that bucindolol may have clinically
important anti-ventricular arrhythmic effects in the roughly 50% of patients
who have the beta-1 389 arginine homozygous genotype, and I believe that
further study of bucindolol in additional clinical trials is warranted."

Will Sauer, M.D., from the University of Colorado Anschutz Medical Campus, an
electrophysiologist-cardiologist and a co-author on the paper, said: "While
the use of beta-blockers as a class of drugs for prevention of ventricular
arrhythmias is not well studied, it is commonly thought that any beta-blocker
is potentially helpful for any at-risk patient. However, the research
presented in our Circulation AEP paper shows that patients with the beta-1 389
arginine homozygous adrenergic receptor polymorphism experienced a 74%
reduction in VT/VF events with the beta-blocker/sympatholytic agent
bucindolol. I believe that these findings have important implications for the
personalized treatment of patients at risk for arrhythmias. In the future,
physicians may look at a patient’s genotype prior to the initiation of a
particular beta-blocker or other anti-arrhythmic. I believe that this is
particularly important in the prevention of lethal arrhythmias like VT or VF,
where the current practice of assuming that any beta-blocker may work could be
harmful; for example, if the prescribed beta blocker is not efficacious or if
a more efficacious beta-blocker for that patient is available."

Michael Bristow, M.D., Ph.D., Cardiologist/clinical pharmacologist and senior
author on the paper, CEO of ARCA, also commented: "This 74% reduction in VT-VF
in the beta-1 389 Arg/Arg subpopulation suggests that Gencaro warrants further
study, such as in heart failure/reduced left ventricular ejection fraction
patients at risk for ventricular arrhythmias, who have implanted
cardioverter-defibrillators that are having appropriate firing. This could
constitute another indication for Gencaro beyond those of atrial fibrillation
prevention and heart failure."

Ventricular tachycardia and ventricular fibrillation are serious, potentially
life-threatening arrhythmias, and the most common cause of sudden cardiac
arrest.

ARCA has been granted patents in the U.S., Europe, and other jurisdictions for
methods of identifying and treating patients with the beta-1 389 arginine
homozygous genotype. The Company plans to conduct a Phase 3 clinical trial to
evaluate Gencaro as a potential treatment for the prevention of AF in patients
with this genotype, including measuring VT/VF data as a secondary endpoint,
subject to receiving the necessary funding.

About ARCA biopharma

ARCA biopharma is dedicated to developing genetically-targeted therapies for
cardiovascular diseases. The Company's lead product candidate, Gencaro^TM
(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. ARCA has
a collaboration with the Laboratory Corporation of America (LabCorp), under
which LabCorp has developed a companion genetic test for Gencaro. 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, 2011 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