June 3, 2010

VHVI to begin trial of novel heart failure therapy

VHVI to begin trial of novel heart failure therapy

Vanderbilt Heart & Vascular Institute is beginning a Phase 1 clinical trial of a novel therapy for heart failure.

In collaboration with Acorda Therapeutics Inc., and with the support of a National Institutes of Health grant, Vanderbilt researchers will study the safety of Glial Growth Factor 2 (GGF2) in patients with systolic heart failure. GGF2 has been shown to protect heart muscle and restore cardiac function in preclinical models of heart failure, myocardial infarction and cardiotoxicity.

"GGF2 may represent a new approach to treating heart failure, and also has potential applications in neurology, which we may investigate in subsequent clinical studies," said Ron Cohen, M.D., President and CEO of Acorda Therapeutics.

GGF2 is part of a family of proteins known as neuregulins that is being developed by Acorda. It acts directly on heart muscle cells, or cardiomyocytes. It is believed to improve the heart's ability to contract by promoting the repair of tissue damage resulting from heart disease or injury. Existing medications for heart failure primarily aim to modify the workload of the heart, rather than promote ventricular repair.

“Vanderbilt will be the first medical center that will give GGF2 to patients in the context of a Phase I-A trial, which is being sponsored by Acorda,” said Doug Sawyer, M.D., Ph.D., Lisa M. Jacobson Professor of Medicine, who has been studying the effect of GGF2 on the heart since 1995.

Doug Sawyer, M.D., Ph.D.

Doug Sawyer, M.D., Ph.D.

“This is an appropriate and successful collaboration with Acorda. If the trial is successful, we will be collaborating in an NIH-approved and funded study where we are getting the best out of both worlds.”

Acorda brings almost a decade of experience with GGF2 in cardiac and neurology research as well as drug development expertise.

Heart failure is a chronic, progressive condition in which the heart muscle is unable to pump enough blood through the heart to meet the body's needs for blood and oxygen. Medication is given to try to prevent the heart muscle from getting weaker. In addition, patients may need a ventricular assist device and eventually a heart transplant.

“In pre-clinical studies, GGF2 appeared to make the endogenous muscle stronger. If you can make the heart muscle stronger, you might prevent some people from getting worse or needing a heart transplant,” Sawyer said.

In the Phase I-A study, led by Daniel Lenihan, M.D., professor of Clinical Medicine, a single dose of GGF2 will be given to heart failure patients and increased over time. It is a safety study so researchers will not be looking at efficacy.

The Phase I-B trial, supported by the NIH and Acorda, will give multiple doses of the drugs over time. Nancy Brown, M.D., professor of Medicine and chief of Clinical Pharmacology, is a co-principal investigator on this study.

Sawyer and Anthony Caggiano, M.D, Ph.D., vice president of preclinical development at Acorda, are co-principal investigators on the NIH grant.

“GGF2 has gotten through a lot of hurdles experimentally, and in animals it's pretty convincing that it improves heart function and promotes survival in the setting of heart failure,” Sawyer said. “It's great to see the work come to clinical trial.”