Data from First Clinical Trial of GGF2 in Heart Failure Presented at the American College of Cardiology 62nd Annual Scientific Session
Acorda Therapeutics, Inc. (Nasdaq: ACOR)
and collaborator Vanderbilt University Medical Center today announced
data from a Phase 1 clinical trial of Glial Growth Factor 2 (GGF2)
designed to study safety, tolerability and exploratory measures of
efficacy in people with heart failure who were already on optimized
regimens of currently available therapies. The study evaluated the
effects of a range of doses, with each participant receiving a single
dose. Data from this trial, which enrolled patients at Vanderbilt and
St. Joseph’s Hospital in Atlanta, GA, are being presented on Sunday,
March 10 at the American College of Cardiology 62nd Annual
Scientific Session in San Francisco, CA.
“We have completed the first in human trial with GGF2 in patients with
heart failure, and especially want to thank our patients who volunteered
for this important study. We are very encouraged by the results,” said
Daniel Lenihan, M.D., Professor of Medicine and Director, Clinical
Research at the Vanderbilt University Medical Center, Division of
Cardiovascular Medicine. “It is notable that trends of long-lasting and
dose-related improvement in cardiac function were seen following a
single dose in patients who were already optimized on standard
therapies. GGF2 warrants further investigation as a treatment for heart
failure.”
“Preclinical studies have suggested that GGF2 may improve heart function
through direct repair of cardiac muscle, a novel mechanism of action.
This first clinical trial in patients with heart failure identified a
maximally tolerated GGF2 dose and key safety parameters to be monitored
in future studies. This information supports continued development of
the compound as a potential treatment for heart failure,” said Anthony
Caggiano, M.D., Ph.D., Vice President of Research and Development at
Acorda.
This was a double-blind, placebo controlled, escalating single dose
clinical trial that included 40 patients with advanced heart failure.
Safety and exploratory efficacy were monitored for 90 days in patients
randomized to receive various doses of GGF2 or placebo.
Safety Findings
In this study, a single dose of GGF2 in patients with heart failure was
generally well tolerated up to 0.75 mg/kg. Among participants receiving
GGF2, the most commonly observed adverse events were headache, site
injection reaction and gastrointestinal symptoms. There were no notable
effects of treatment on hematology or electrocardiogram, and no adverse
events led to withdrawal from the study.
A dose-limiting adverse event of hepatotoxicity (liver injury) meeting
Hy’s Law criteria (elevated ALT, AST and bilirubin) occurred in the
highest-dose cohort. The patient’s liver function tests and bilirubin
had returned to normal by two weeks after dosing. There was also one
reported case of uroepithelial carcinoma, a form of cancer in the cells
that line the bladder, which was diagnosed three months after dosing in
the highest-dose cohort. The patient’s baseline urinalysis showed the
presence of red blood cells, indicating that the tumor was likely
present prior to dosing.
Ejection Fraction Findings
A left ventricle ejection fraction of 55% or higher is considered
normal; all participants in the Phase 1 GGF2 trial had left ventricle
ejection fraction of less than 40%. Trial participants receiving GGF2
showed a consistent and dose-responsive trend towards improving left
ventricular ejection fraction over 28 and 90 days compared to placebo.
Mean ejection fractions at screening in the treatment and placebo groups
were 27% and 29%, respectively. For the cohort receiving the maximally
tolerated dose (0.75 mg/kg) of GGF2, the mean ejection fraction at
screening was 28% and the absolute mean changes in ejection fraction at
day 8, day 14, day 28, and day 90 were 5%, 12%, 12.0% and 9.0%, compared
to absolute mean changes of -1%, -1%, 0% and 2% for the placebo group;
thus, the mean ejection fraction for this GGF2 group at day 28 was 40%,
versus 29% for placebo.
Acorda has discussed the findings from this initial study with the U.S.
Food and Drug Administration (FDA) and has reached agreement on the next
clinical study of GGF2 in heart failure. This study will primarily
investigate further the safety profile of GGF2 across a range of doses,
and will continue to explore efficacy outcomes.
The FDA has granted Fast Track designation for GGF2 for the treatment of
heart failure.
About GGF2
GGF2 is the leading development candidate from Acorda’s neuregulin
program. Neuregulins are a class of naturally occurring protein growth
factors that have multiple effects on the nervous and cardiovascular
systems.
Preclinical studies demonstrate that GGF2 acts directly to repair
cardiac muscle and improve its contractile function. No currently
available therapies do this, and GGF2 may therefore offer an important
new treatment option for people with heart failure.
In addition to its clinical program in heart failure, the Company also
has preclinical development programs for GGF2 in a number of
neurological indications, including peripheral nerve injury and stroke.
About Acorda
Therapeutics
Acorda Therapeutics is a biotechnology company focused on developing
therapies that restore function and improve the lives of people with MS,
spinal cord injury and other neurological conditions.
Acorda markets AMPYRA®
(dalfampridine) Extended Release Tablets, 10 mg, in the United
States as a treatment to improve walking in patients with multiple
sclerosis (MS). This was demonstrated by an improvement in walking
speed. AMPYRA is marketed outside the United States as FAMPYRA®
(prolonged-release fampridine tablets) by Biogen Idec under a licensing
agreement from Acorda. AMPYRA and FAMPYRA are manufactured under license
from Alkermes Pharma Ireland Limited.
The Company also markets ZANAFLEX
CAPSULES® (tizanidine hydrochloride) and Zanaflex
tablets, a short-acting drug for the management of spasticity. Acorda
also receives sales royalties on tizanidine hydrochloride capsules, an
authorized generic version of ZANAFLEX CAPSULES, distributed by Actavis,
Inc. under its agreement with Acorda.
Acorda has an industry-leading pipeline of novel neurological therapies.
The Company is developing Diazepam Nasal Spray for treatment of certain
epileptic seizures. It is also studying AMPYRA to improve a range of
functional impairments caused by MS, as well as its potential for use in
other neurological conditions, including cerebral palsy and post-stroke
deficits. In addition, Acorda is developing clinical stage compounds
AC105 for acute treatment of spinal cord injury, GGF2 for treatment of
heart failure and rHIgM22, a remyelinating monoclonal antibody, for the
treatment of MS. GGF2 is also being investigated in preclinical studies
as a treatment for neurological conditions such as stroke and spinal
cord injury. Chondroitinase, an enzyme that encourages nerve plasticity
in spinal cord injury, is in preclinical development.
Acorda Forward-Looking Statements
This press release includes forward-looking statements within the
meaning of the Private Securities Litigation Reform Act of 1995. All
statements, other than statements of historical facts, regarding
management's expectations, beliefs, goals, plans or prospects should be
considered forward-looking. These statements are subject to risks and
uncertainties that could cause actual results to differ materially,
including our ability to successfully market and sell Ampyra in the
U.S.; third party payers (including governmental agencies) may not
reimburse for the use of Ampyra or our other products at acceptable
rates or at all and may impose restrictive prior authorization
requirements that limit or block prescriptions; the risk of unfavorable
results from future studies of Ampyra or from our other research and
development programs, including Diazepam Nasal Spray or any other
acquired or in-licensed programs; we may not be able to complete
development of, obtain regulatory approval for, or successfully market
Diazepam Nasal Spray or other products under development; the occurrence
of adverse safety events with our products; delays in obtaining or
failure to obtain regulatory approval of or to successfully market
Fampyra outside of the U.S. and our dependence on our collaboration
partner Biogen Idec in connection therewith; competition, including the
impact of generic competition on Zanaflex Capsules revenues; failure to
protect our intellectual property, to defend against the intellectual
property claims of others or to obtain third party intellectual property
licenses needed for the commercialization of our products; failure to
comply with regulatory requirements could result in adverse action by
regulatory agencies; and the ability to obtain additional financing to
support our operations. These and other risks are described in greater
detail in Acorda Therapeutics' filings with the Securities & Exchange
Commission. Acorda may not actually achieve the goals or plans described
in its forward-looking statements, and investors should not place undue
reliance on these statements. Forward-looking statements made in this
release are made only as of the date hereof, and Acorda disclaims any
intent or obligation to update any forward-looking statements as a
result of developments occurring after the date of this release.
