ARCA biopharma, Inc. (Nasdaq:ABIO), a biopharmaceutical company
applying a precision medicine approach to developing
genetically-targeted therapies for cardiovascular diseases, today
announced that data from the GENETIC-AF clinical trial was
presented in a “Late Breaking Clinical Trials” oral presentation at
the European Society of Cardiology Heart Failure 2018 World
Congress on Sunday May 27, 2018. William T. Abraham, M.D.,
Professor of Medicine, Physiology and Cell Biology and Director,
Division of Cardiovascular Medicine at the Ohio State University
presented the data. The presentation is available at
http://arcabio.com/investors/investor-presentations/.
In the overall study population of heart failure
patients who were at high risk for recurrent atrial fibrillation
(AF), pharmacogenetic guided GencaroTM did not reduce AF/AFL/ACM
recurrence compared to the active comparator TOPROL-XL. However, in
U.S. patients (48% of the entire cohort), a trend for potential
benefit in favor of Gencaro (approximately 30% risk reduction over
TOPROL-XL), was observed for the primary endpoint of all-cause
mortality (ACM) or time to recurrence of AF or atrial flutter
(AFL). A trend for potential benefit in favor of Gencaro was
also observed in a subset of patients from the U.S., Canada and
Europe who underwent continuous heart rhythm monitoring with
Medtronic implanted devices (approximately 25% risk reduction over
TOPROL-XL). Safety data indicated that Gencaro was well-tolerated
in the AF-HFrEF population investigated with a safety profile
similar to TOPROL-XL.
“With additional analysis of the trial data, and
taking into consideration recent studies in animal models of AF, it
is likely that AF-HFrEF phenotypic differences are responsible for
the heterogeneity in treatment response observed. These Phase 2B
data support and provide guidance for potential additional
development of Gencaro as a treatment for atrial fibrillation in
patients with heart failure, an indication for which there are
currently no FDA approved therapeutics,” commented Dr. Abraham.
GENETIC-AF was a Phase 2B, double-blind,
superiority clinical trial evaluating Gencaro (bucindolol
hydrochloride) as a genetically-targeted treatment for AF in
patients with HF and reduced left ventricular ejection fraction
(HFrEF). The trial enrolled 267 patients from the United States,
Canada and Europe.
The primary analysis was conducted to evaluate
the evidence of safety and efficacy of Gencaro versus an active
comparator with demonstrated effectiveness and safety in this
patient population TOPROL-XL. The primary endpoint of the trial was
time to recurrent AF, atrial flutter (AFL) or all-cause mortality
(ACM). The trial was not powered to conventional significance for
this endpoint and utilized Bayesian statistical modeling of
predictive probability of success (PPoS) of the primary endpoint to
estimate outcome if the trial had enrolled 620 patients with 330
primary events.
Gencaro was generally safe and well-tolerated,
with 84% of patients attaining their target dose compared to 72% of
patients receiving TOPROL-XL. The most frequently reported adverse
events were similar in both groups and consistent with the known
safety profile of the beta-blocker class of drugs. Adverse events
assessed as related to study drug by the investigator occurred in
23.8% of patients in the Gencaro group and in 30.1% of patients in
the TOPROL-XL group. Of note, adverse events of bradycardia were
less frequently reported in the Gencaro group (3.7%) compared to
patients receiving TOPROL-XL (12.0%). During the 24-week efficacy
follow-up period there were three deaths (ACM) in the TOPROL-XL
group and none in the Gencaro group. Three patients died in the
long-term treatment extension period after receiving Gencaro for
more than a year.
In the overall study population, pharmacogenetic
guided Gencaro did not reduce AF/AFL/ACM recurrence compared to the
active comparator TOPROL-XL (143 total events, hazard ratio of 1.01
(95% confidence interval: 0.71, 1.42), which was associated with a
PPoS of 14%. In the U.S. patient cohort of 127 patients
(approximately 50% of all patients and events), a trend for
potential superior benefit in favor of Gencaro over TOPROL-XL was
observed (73 events, hazard ratio 0.70, [95% confidence interval:
0.41, 1.19]), with a PPoS of 61%, which was greater than the
prespecified criteria set by the company to proceed to Phase 3
development.
The Company believes the difference in treatment
response between the overall and U.S. patient cohorts was primarily
due to the inclusion of a higher number of patients with
long-standing AF who had asymptomatic/mild heart failure in two
countries exhibiting hazard ratios >1.0 for the primary
endpoint. In a subgroup analysis that excluded these patients
(77% of the overall study population), a trend for potential
benefit in favor of Gencaro was observed (17% risk reduction over
TOPROL-XL). The Company believes this type of population, in which
AF is being driven by underlying HF pathophysiology, would be the
focus of any future clinical trials of Gencaro.
An End-of-Phase 2 meeting is scheduled with the
U.S. Food and Drug Administration (FDA) for the last week of
June to review the GENETIC-AF data and potential future Gencaro
development plans. Within 30 days following the meeting, the
FDA will provide written minutes of the meeting to confirm the
discussions. ARCA plans to provide an update on Gencaro
potential future development plans subsequent to receiving the FDA
meeting minutes.
About GENETIC-AF
A Genotype-Directed Comparative
Effectiveness Trial of Bucindolol
and TOPROL-XL for Prevention of Symptomatic Atrial
Fibrillation/Atrial Flutter in Patients with Heart
Failure
GENETIC-AF was a Phase 2B multi-center,
randomized, double-blind, clinical superiority trial comparing the
safety and efficacy of Gencaro™ against an active comparator, the
beta-blocker TOPROL-XL (metoprolol succinate) for the treatment and
prevention of recurrent atrial fibrillation or flutter (AF/AFL) in
heart failure patients with reduced left ventricular ejection
fraction (HFrEF). Eligible patients had HFrEF, a history of
paroxysmal AF (episodes lasting 7 days or less) or persistent AF
(episodes lasting more than 7 days and less than 1 year) in the
past 6 months, and the beta-1 389 arginine homozygous genotype that
we believe responds most favorably to Gencaro™. A subset of
patients in the trial also underwent continuous heart rhythm
monitoring to assess AF burden, which is defined as the amount of
time per day that a patient experiences AF. Topline results of
GENETIC-AF were reported on February 26, 2018.
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 patients
with atrial fibrillation (AF) and chronic heart failure with
reduced left ventricular ejection fraction (HFrEF) which recently
completed a Phase 2B clinical trial. 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. ARCA has a
collaboration with Medtronic, Inc. for support of the GENETIC-AF
trial. The Gencaro development program has been granted Fast Track
designation by FDA. ARCA also plans to develop AB171, a
thiol-substituted isosorbide mononitrate, as a potential
genetically-targeted treatment for peripheral arterial disease
(PAD) and for heart failure (HF). 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, statements regarding the ability of ARCA’s
financial resources to support its operations through the end of
2018, potential future development plans for Gencaro, the expected
features and characteristics of Gencaro or AB171, including the
potential for genetic variations to predict individual patient
response to Gencaro, Gencaro’s potential to treat AF, AB171’s
potential to treat HF, 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, 2017, 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
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