-------------------------------------------------------------------------------------------------- Gencaro
Demonstrates Comparable Efficacy to Active Control
and Trend for Potential Gencaro Superiority
in US Patient
Cohort-------------------------------------------------------------------------------------------------- ARCA
Anticipates Meeting with the U.S. FDA in the Second Quarter of
2018 to Review Phase 2 Data and Phase 3
Development
Plan-------------------------------------------------------------------------------------------------- Management
to Host Conference Call & Webcast Today at 9:00 am
ET
ARCA biopharma, Inc. (Nasdaq:ABIO), a clinical-stage
biopharmaceutical company applying a precision medicine approach to
developing genetically-targeted therapies for cardiovascular
diseases, today announced clinical results from GENETIC-AF, a Phase
2B, double-blind, superiority clinical trial evaluating GencaroTM
(bucindolol hydrochloride) as a genetically-targeted treatment for
atrial fibrillation (AF) in patients with heart failure and reduced
left ventricular ejection fraction (HFrEF). In all patients,
Gencaro demonstrated a similar treatment benefit compared to the
active control, metoprolol succinate (TOPROL-XL). In U.S. patients
(127 of 267 total patients), a trend for potential superior benefit
in favor of Gencaro (approximately 30% risk reduction over
TOPROL-XL), was observed for the primary endpoint of time to
recurrence of AF. Additionally, in U.S. patients, Gencaro
demonstrated a trend for potential superior benefit in favor of
Gencaro (approximately 51% risk reduction over TOPROL-XL) in a
subset of patients who underwent continuous heart rhythm monitoring
with Medtronic implanted devices. Safety data indicated that
Gencaro was generally safe and well-tolerated in the AF/heart
failure (HF) population investigated with a safety profile similar
to TOPROL-XL.
GENETIC-AF enrolled 267 patients from the United
States, Canada and Europe. The primary analysis was conducted to
evaluate the evidence of safety and superior efficacy of Gencaro
versus an active control 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.
In all patients, Gencaro demonstrated a similar
treatment benefit compared to the active control, 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 effects between the overall and U.S. patient cohorts
was primarily due to results in two non-U.S. countries exhibiting
hazard ratios >1.0. The differences between patients enrolled at
these sites versus the U.S. and other country cohorts are being
investigated.
“The U.S. data support our pre-trial assumptions
and provide contemporary information to potentially design Phase 3
development of Gencaro,” commented Dr. Debra Marshall, Senior
Vice-President of Medical Affairs. “I would like to thank our
clinical investigators, as well as the patients and their families,
for their participation in this study.”
A subgroup of patients underwent continuous
(24/7) heart rhythm monitoring via Medtronic implanted loop
recorders or other Medtronic implanted therapeutic devices (e.g.,
ICDs, CRTs) to evaluate daily AF burden. AF burden is defined as
the amount of time per day a patient experiences AF. A prespecified
time-to-first event analysis was conducted using a total AF burden
of at least 6 hours per day to define an event of AF recurrence. In
this analysis, hazard ratios of 0.75 (0.43, 1.32) and 0.49 (0.24,
1.04) were observed in the overall (n=69) and U.S. patient (n=42)
cohorts, respectively.
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.
“We are pleased to share these results from our
GENETIC-AF clinical trial. It should be emphasized that the control
drug in the study, TOPROL-XL, although not FDA approved for this
indication, has demonstrated efficacy in preventing AF in HFrEF.
While we did observe some regional heterogeneity in effectiveness
of Gencaro, we believe the treatment response observed in the U.S.
population, which represents approximately half of the overall
study population, support continued development of Gencaro as a
genetically-targeted treatment for atrial fibrillation,” commented
Dr. Michael Bristow, ARCA’s President and CEO. “As in all Phase 2
trials, which in part are conducted to elicit information relevant
to the design for Phase 3, elucidation of the reason(s) for
regional heterogeneity could prove valuable for Phase 3 trial
design.”
ARCA anticipates meeting with the U.S. Food and
Drug Administration (FDA) in the second quarter of 2018 to review
Gencaro Phase 2 data and potential Phase 3 development plan.
ARCA ended 2017 with cash, cash equivalents and
marketable securities totaling $11.8 million (unaudited) and
believes that these funds, with additional net proceeds of
approximately $3.4 million (unaudited) raised in January 2018
through its existing “At-the-Market” offering facility, will be
sufficient to fund its operations, at its projected cost structure,
through the end of 2018.
GENETIC-AF Clinical Trial
GENETIC-AF is a Phase 2B, multi-center,
randomized, double-blind, superiority clinical trial comparing the
safety and efficacy of Gencaro to Toprol-XL (metoprolol succinate)
for the treatment and prevention of recurrent atrial fibrillation
or atrial 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 ARCA believes responds most favorably to Gencaro.
Conference Call and Webcast
ARCA will hold a conference call and live audio
webcast today, Monday, February 26, 2018 at 9:00 am Eastern (7:00am
Mountain) to discuss results from the GENETIC-AF clinical
trial.
Participant Toll-Free Dial-In Number:
1-877-270-2148
Participant International Dial-In Number:
1-412-902-6510
Ask to be joined into the ARCA biopharma
call.
Presentation slides to accompany the conference
call have been posted to the Presentations page in the investor
section of the ARCA website, www.arcabio.com.
Interested parties may access a live audio
webcast of the conference call at:
https://services.choruscall.com/links/abio180226.html. Please
connect to the ARCA website several minutes prior to the start of
the broadcast to ensure adequate time for any software download
that may be necessary. The webcast will be archived for 90
days.
About GencaroTM (bucindolol
hydrochloride)
Gencaro (bucindolol hydrochloride) is an
investigational, pharmacologically unique beta-blocker and mild
vasodilator being developed for the treatment of AF. Gencaro is
considered part of the beta-blocker class of compounds because of
its property of blocking both beta-1 and beta-2 receptors in the
heart. The blocking of these receptors prevents them from binding
with other molecules, primarily the neurotransmitter
norepinephrine, which activate these receptors. ARCA believes that
Gencaro is well-tolerated in cardiovascular patients because of its
mild vasodilator effects. Originally developed by Bristol-Myers
Squibb, the active pharmaceutical ingredient in Gencaro, bucindolol
hydrochloride, has been tested clinically in approximately 4,500
patients, including over 3,250 patients in eight clinical trials in
HFrEF patients. Gencaro was the subject of a Phase 3 HF mortality
trial in 2,708 patients, mostly in the United States (the “BEST
trial”). The BEST trial included a DNA bank of over 1,000 patients,
which was used to evaluate the effect of genetic variation on
patients’ response to Gencaro.
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 AF and 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 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 potential Phase 3
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 AF, future treatment options for
patients with AF, the potential for Gencaro to be the first
genetically-targeted AF prevention treatment and the ability of
ARCA’s financial resources to support its operations through the
end of 2018. 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, 2016, and
subsequent filings. ARCA disclaims any intent or obligation to
update these forward-looking statements.
A photo accompanying this announcement is available at
http://www.globenewswire.com/NewsRoom/AttachmentNg/af496e97-20da-420a-bf93-e51b3a3ed740
Investor & Media
Contact:Derek Cole720.940.2163derek.cole@arcabio.com
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