New Adaptive Phase 3 Trial Planned for GencaroTMin Atrial Fibrillation
BROOMFIELD, Colo. -- January 29, 2013
ARCA biopharma, Inc. (Nasdaq: ABIO), a biopharmaceutical company developing
genetically-targeted therapies for atrial fibrillation, heart failure and
other cardiovascular diseases, today provided an update on a proposed,
genetically-targeted clinical trial in atrial fibrillation (“AF”) of the
Company’s lead developmental drug, Gencaro (bucindolol hydrochloride). The
Company also announced that Medtronic, Inc., a leader in medical technologies
to improve the treatment of chronic diseases, including cardiac rhythm
disorders, has signed a non-binding Letter of Intent to collaborate on the
initial, Phase 2B portion of the proposed trial.
The Proposed GENETIC-AF Phase 3 Adaptive Design Clinical Trial
The trial, known as GENETIC-AF, is projected to be a 620-patient, Phase 3
study comparing Gencaro to metoprolol CR/XL for prevention of AF in patients
with heart failure and left ventricular dysfunction ("HFREF"). The Trial is
planned to be genetically enriched by enrolling only those patients who
possess the cardiac beta-1 adrenergic receptor genotype 389 arginine
homozygous, which in the Beta Blocker Evaluation of Survival Trial ("BEST")
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,
over 24 weeks post electrical cardioversion for persistent AF. Commencement of
the GENETIC-AF is conditional on receipt of the necessary funding, which ARCA
intends to secure through equity financing or a strategic partnership.
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.
ARCA believes that Gencaro has potential as a treatment for AF, based on
placebo-controlled data from the Phase 3 heart failure BEST study. A
retrospective analysis of data from the BEST Trial shows that patients with
the genotype that ARCA plans to enroll in GENETIC-AF 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
AF is considered an epidemic cardiovascular disease with an estimated
prevalence of at least 2.7 million Americans in 2010. In HFREF patients, the
approved therapies for the treatment or prevention of AF have disadvantages,
such as toxic or cardiovascular adverse effects, and most of the approved
drugs are contra-indicated or have warnings in their prescribing information.
ARCA believes there is an unmet medical need for new AF treatments that are
safe and more effective in the HFREF population at risk for AF.
ARCA has received guidance from the Food and Drug administration (“FDA”)
regarding a Phase 3 clinical study comparing Gencaro to metoprolol for the
prevention of AF in approximately 600 HFREF patients, with a design similar to
GENETIC-AF, but without an adaptive feature. Based on this FDA guidance, the
Company believes that a successful Phase 3 clinical study similar to
GENETIC-AF, with a p-value of less than 0.01, could be sufficient evidence of
efficacy upon which to base a New Drug Application (“NDA”) for the approval of
Gencaro for an AF indication in HFREF patients. ARCA plans to obtain further
guidance from the FDA, which may affect the trial’s design.
The proposed collaboration with Medtronic involves a substudy of the Phase 2B
portion of GENETIC-AF that will measure the AF burden data by means of the
continuous monitoring devices. Under the proposed collaboration, Medtronic
would provide support associated with the AF burden substudy and with
collection and analysis of the substudy data.
Dr. Michael Bristow, MD, PhD., President and Chief Executive Officer of ARCA,
said, “We at ARCA are excited about the new adaptive design for GENETIC-AF and
the potential to use AF burden measured by previously implanted devices as
well as by newly inserted implantable loop recorders, which we believe
represent the next generation of diagnosis and treatment options for patients
at risk for AF. AF is a serious disorder that increases the risk of stroke and
mortality, and in HFREF patients often heralds the worsening of heart failure.
There is a need for new treatment options, particularly for patients with
HFREF. The GENETIC-AF trial has the potential to result in an approvable new
therapy that is safe and effective for HFREF patients at high risk for AF. We
believe that the use of continuous monitoring devices including implantable
loop recorders to monitor AF burden in the Phase 2B substudy will result in
many more clinically-relevant events, which will potentially increase the
power and usefulness of the data. We believe that AF burden used in
conjunction with drug therapy will become an increasingly important tool in
the diagnosis and treatment of AF.”
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 likelihood of
completing a definitive agreement with Medtronic for support of the planned
trial, genetic variations to predict individual patient response to Gencaro,
Gencaro’s potential to treat atrial fibrillation, future treatment options for
patients with atrial fibrillation, the number of events recorded by
implantable loop recorders, the role of AF burden in diagnosis and treatment
of 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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