Unmet Medical Need in Treatment of Heart Failure Patients with Atrial
Fibrillation Highlighted in Articles in Inaugural Issue of JACC: Heart
New Meta-Analysis Suggests Currently Approved Beta-Blockers Have Little or No
Beneficial Effects in Heart Failure Patients with Atrial Fibrillation
Editorial Cites Unmet Medical Therapy Need, Calls for Development of New
BROOMFIELD, Colo. -- February 6, 2013
ARCA biopharma, Inc. (Nasdaq: ABIO), a biopharmaceutical company developing
genetically-targeted therapies for atrial fibrillation, heart failure and
other cardiovascular diseases, today announced that the editorial “Treatment
of the Heart Failure Patient with Atrial Fibrillation: A Major Unmet Need” was
published in the first edition of JACC: Heart Failure, a new journal of the
American College of Cardiology
The editorial, authored by ARCA’s President and Chief Executive Officer, Dr.
Michael Bristow, and Dr. Ryan Aleong of the University of Colorado, discusses
the authors’ views that the treatment of atrial fibrillation (“AF”) in heart
failure (“HF”) patients with reduced left ventricular ejection fractions
(“HFREF”) is a major unmet need in cardiovascular therapies and should be
approached differently from current treatments for HFREF patients with sinus
The article is an accompanying editorial to “Beta-Blockers and Outcome in
Heart Failure and Atrial Fibrillation: A Meta-Analysis,” by Michiel Rienstra,
MD, et al.
(http://heartfailure.onlinejacc.org/article.aspx?articleid=1568318), in the
same edition of JACC: Heart Failure, which examined the results of four major
Phase 3 HFREF trials of the four beta-blockers (carvedilol, metoprolol,
bisoprolol and nebivolol) that are currently approved for the treatment of HF.
The authors of the meta-analysis report conclude that the evidence indicates
that the evaluated beta-blockers provided little or no benefit to HFREF
patients with AF in these trials.
The Rienstra report did not include data from the published Phase 3 clinical
study of Gencaro (bucindolol hydrochloride) known as the Beta Blocker
Evaluation of Survival Trial (“BEST”)
(http://www.ncbi.nlm.nih.gov/pubmed/23223178). The Bristow/Aleong editorial
comments that the data from BEST appear to be different from the data for the
drugs evaluated in the Rienstra study, because retrospective analyses of the
data from BEST appear to show evidence of efficacy for Gencaro in HFREF
patients with AF, and enhanced efficacy for those HFREF patients with AF who
possess a common genetic variant in the cardiac beta-1 adrenergic receptor
(AR), the primary drug target of beta-blockers for cardiovascular indications.
The editorial authors discuss several reasons why the data for Gencaro in
HFREF patients with AF appear to be different from that for the beta-blockers
analyzed in the Rienstra paper, including Gencaro’s unique mechanisms of
action. The editorial also notes that the use of anti-arrhythmic drugs to
treat AF in HFREF patients is problematic due to the high frequency of
pro-arrhythmia and adverse effects on left ventricular function associated
with these drugs. The authors highlight the potential significance of the
medical need represented by HFREF patients with AF, noting that the two
diseases commonly occur together (19% of the HFREF patients in the trials
analyzed by Rienstra had AF and other reports have estimated up to 40% of
HFREF patients have AF), and the evidence that AF worsens mortality in HFREF
patients. The editorial concludes by stating: "At a minimum, . . . AF-HFREF
treatment should be approached differently from that for SR-HFREF, via
therapies uniquely suited to dealing with this important subpopulation."
As previously reported, ARCA believes that Gencaro has potential as a
treatment for AF. A retrospective analysis of data from the BEST Trial shows
that HFREF patients with the genetic variation in the beta-1 AR that ARCA
believes enhances response to Gencaro had a 74% reduction in the risk of AF
compared to placebo (p = 0.0003). These same patients experienced a 38%
reduction in the risk of all cause mortality (p < 0.05) and statistically
significant improvements on other major clinical efficacy endpoints.
Based on these data ARCA recently announced its plans to conduct a Phase 3
clinical trial of approximately 620 patients comparing Gencaro to metoprolol
CR/XL for the prevention of AF in HFREF patients, known as GENETIC-AF. The
trial is planned to be genetically enriched by enrolling only those patients
who possess the cardiac beta-1 AR genotype 389 arginine homozygous, which in
the BEST Trial was associated with an enhanced response to Gencaro in
preventing atrial fibrillation. The Company estimates that this genotype is
present in about 50% of the U.S. population. The primary endpoint of
GENETIC-AF is planned to be the combination endpoint of recurrent symptomatic
AF and all-cause mortality. The clinical endpoints planned for GENETIC-AF also
include secondary endpoints to assess rate control and HF morbidity and
mortality in patients who develop permanent AF.
ARCA has created an adaptive design for GENETIC-AF, under which the Company
plans to initiate a Phase 2B study in approximately 200 HFREF patients.
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.
A secondary endpoint of the proposed Phase 2B portion of the trial will be AF
burden, defined as a patient’s actual time in AF, regardless of symptoms.
Under the Company’s proposed design, all 200 patients in the Phase 2B portion
of the trial will have AF burden measured by continuous monitoring, either by
previously implanted cardiac resynchronization or defibrillation devices, or
newly or previously inserted implantable loop recorders. At the end of
enrollment of the first 200 patients, the primary endpoint of recurrent
symptomatic AF and all-cause mortality, and the secondary endpoint of AF
burden will be evaluated by the trial’s Data and Safety Monitoring Board for
evidence of an efficacy signal. If a sufficient efficacy signal is detected
and acceptable safety is observed, the trial would then proceed to the Phase 3
portion and full enrollment. Commencement of GENETIC-AF is conditional on
receipt of the necessary funding, which ARCA intends to secure through equity
financing or a strategic partnership.
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, 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.
ARCA biopharma, Inc.
Christopher D. Ozeroff, 720-940-2100
Senior Vice President and General Counsel
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