ARDSLEY, N.Y. & NASHVILLE, Tenn.–Mar. 7, 2013– 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.

GGF2 is the leading development candidate from Acorda’s neuregulin program.

“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.