Unmet Medical Need in Treatment of Heart Failure Patients with Atrial Fibrillation Highlighted in Articles in Inaugural Issue of JACC: Heart Failure
Editorial Cites Unmet Medical Therapy Need, Calls for Development
of New Therapies
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
(http://heartfailure.onlinejacc.org/article.aspx?articleid=1568319).
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 rhythm.
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,
GencaroTM (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.