GENETIC-AF Phase 2B Trial Results Published in the Journal of American College of Cardiology: Heart Failure
May 01 2019 - 8:30AM
ARCA biopharma, Inc. (Nasdaq: ABIO), a biopharmaceutical company
applying a precision medicine approach to developing
genetically-targeted therapies for cardiovascular diseases, today
announced that the paper “GENETIC-AF: Bucindolol for the
Maintenance of Sinus Rhythm in a Genotype-Defined Heart Failure
Population” was published in JACC: Heart Failure, a journal of the
American College of Cardiology.
The lead author on the paper is Jonathan P.
Piccini, MD, MHS, FACC, Director, Duke Center for Atrial
Fibrillation, Duke University Medical Center and Duke Clinical
Research Institute and the senior author is Stuart J. Connolly, MD,
Professor Emeritus, Division of Cardiology at McMaster University
in Hamilton, Ontario.
“Atrial fibrillation (AF) is a common and
serious medical problem associated with significant morbidity and
mortality, especially in patients with heart failure (HF),” said
Dr. Michael R. Bristow, President and Chief Executive Officer of
ARCA and a co-author on the paper. “Development of AF is
associated with increased risk of adverse cardiovascular outcomes,
and when AF occurs in patients with HF these adverse effects are
accentuated. AF and HF often co-exist and have common risk
factors, as well as overlapping pathophysiologies.”
Bucindolol is a beta-blocker whose unique
pharmacologic properties provide greater benefit in HF patients who
have the beta-one adrenergic receptor (ADRB1) Arg389Arg
genotype. GENETIC-AF compared the effectiveness of bucindolol
and metoprolol succinate for the maintenance of sinus rhythm in a
genetically-defined HF population with AF. The trial enrolled
267 HF patients with a left ventricular ejection fraction (LVEF)
< 0.50, symptomatic AF, and the ADRB1 Arg389Arg genotype. The
primary endpoint of AF/atrial flutter (AFL) or all-cause mortality
(ACM) was evaluated by electrocardiogram (ECG) during a 24-week
period.
The hazard ratio (HR) for the primary endpoint
was neutral (1.01 (95% CI: 0.71, 1.42)) but trends for bucindolol
benefit were observed in several subpopulations. Precision
therapeutic phenotyping revealed that a differential response to
bucindolol was associated with: 1) the interval of time from the
initial diagnosis of HF and AF to randomization, and: 2) the onset
of AF relative to initial HF diagnosis. In a cohort whose first HF
and AF diagnoses were less than 12 years prior to randomization, in
which AF onset did not precede HF by more than 2 years (N=196), the
HR was 0.54 (95% CI: 0.33, 0.87; p = 0.011). Moreover, in the HF
with mid-range LVEF subpopulation, which comprised approximately
50% of randomized patients, the HR was 0.42 (0.21, 0.86); p =
0.017.
As expected based on its unique pharmacology,
bucindolol reduced plasma venous norepinephrine levels (by 124
pg/ml at 4 weeks, p <0.001) while metoprolol did not (p =0.30).
Plasma NT-proBNP, a biomarker of both AF and HF, was reduced in the
bucindolol group at 4 weeks (p= 0.003), 12 weeks (p = 0.002) and 24
weeks (p = 0.005) while in the metoprolol group a reduction was
observed only at 24 weeks (p = 0.014).
“In this exploratory Phase 2 trial,
pharmacogenetic-guided bucindolol therapy did not reduce the
recurrence of AF/AFL/ACM compared to metoprolol in a broad
population of HF patients at risk of AF,” concluded Dr. Piccini,
“however, the majority of patients in this trial demonstrated a
more favorable response to genetically-targeted bucindolol compared
to standard beta-blocker therapy. These data are very encouraging
and merit further investigation in future Phase 3 trials.”
“The precision therapeutic phenotyping
methodology used in these analyses identified broad relationships
that consistently manifested across the entire dataset.” commented
Christopher Dufton, PhD, Vice President of Clinical Development at
ARCA and a co-author, “As such, we believe this approach increases
the likelihood of reproducibility of these results in future Phase
3 trials.”
About ARCA biopharma
ARCA biopharma is dedicated to developing
genetically-targeted therapies for cardiovascular diseases through
a precision medicine approach to drug development. ARCA’s lead
product candidate, GencaroTM (bucindolol hydrochloride), is an
investigational, pharmacologically unique beta-blocker and mild
vasodilator being developed for the potential treatment of atrial
fibrillation in heart failure patients with mid-range ejection
fraction. 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 AF prevention
treatment. The Gencaro development program has been granted
Fast Track designation by FDA. ARCA is also developing AB171, a
thiol-substituted isosorbide mononitrate, as a potential
genetically-targeted treatment for heart failure and peripheral
arterial disease (PAD). For more information, please visit
www.arcabio.com.
Safe Harbor Statement
This press release contains "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, potential future development plans for
Gencaro, the expected features and characteristics of Gencaro,
including the potential for genetic variations to predict
individual patient response to Gencaro, Gencaro’s potential to
treat atrial fibrillation (AF), future treatment options for
patients with AF, and the potential for Gencaro to be the first
genetically-targeted AF 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: ARCA’s financial resources
and whether they will be sufficient to meet its business objectives
and operational requirements; ARCA may not be able to raise
sufficient capital on acceptable terms, or at all, to continue
development of Gencaro or to otherwise continue operations in the
future; results of earlier clinical trials may not be confirmed in
future trials; the protection and market exclusivity provided by
ARCA’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 Securities and Exchange Commission, including without
limitation ARCA’s annual report on Form 10-K for the year ended
December 31, 2018, and subsequent filings. ARCA disclaims any
intent or obligation to update these forward-looking
statements.
Investor & Media
Contact:Derek Cole720.940.2163derek.cole@arcabio.com
A photo accompanying this announcement is available at
http://www.globenewswire.com/NewsRoom/AttachmentNg/af496e97-20da-420a-bf93-e51b3a3ed740
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