Neuregulins are a class of naturally occurring protein growth factors that have multiple effects on the nervous and cardiovascular systems. Acorda is developing its lead recombinant neuregulin candidate, cimaglermin alfa, in a number of nervous system and cardiac indications, including heart failure, stroke and peripheral nerve injury. The most advanced of these is a clinical-stage program in heart failure.
Acorda completed a Phase 1 clinical trial of cimaglermin in heart failure patients in late 2012. The trial was designed to study safety and tolerability in a single ascending dose of cimaglermin in people with heart failure who were already on optimized regimens of currently available cardiovascular therapies. Several exploratory measures of efficacy were also included in the trial protocol. Data from the trial were presented at the American College of Cardiology 62nd Annual Scientific Session in March 2013. Further analyses from this same trial were presented at the American College of Cardiology 64th Annual Scientific Session in March 2015.
In October 2013, Acorda initiated a second Phase 1b clinical trial of cimaglermin in heart failure. In June, we announced that we had stopped enrollment in the trial based on the occurrence of a case of hepatotoxicity (liver injury) meeting Hy’s Law criteria, based on blood test results. Acorda also received a notification of clinical hold from the FDA following the submission of this information. There was one Hy’s Law case reported in the previous Phase 1 study. In both cases the abnormal blood tests resolved within several days. The 22 patients who were dosed in the trial will complete the pre-planned one year of follow up. We expect to complete an analysis of data from the three-month follow up by the end of the year. Acorda has ongoing analyses and non-clinical studies to investigate the biological basis for liver interactions of cimaglermin, and plans to review these and other data from the cimaglermin studies with the FDA.
Heart failure is a chronic, progressive condition in which the heart muscle is unable to pump enough blood to meet the body’s need for oxygen. Heart failure is most commonly the result of damage to the heart, caused by coronary artery disease or from added stress to the heart from other health conditions, such as diabetes or high blood pressure. Approximately 5.1 million people in the U.S. have heart failure. The Center for Disease Control and Prevention (CDC) reports that about half of people who develop heart failure will die within 5 years of their diagnosis.
Existing medications aim to compensate for the heart’s diminished blood pumping ability, but do not directly restore heart muscle function. Cimaglermin acts at the level of the muscle cells, or cardiomyocytes, and may be able to restore cardiomyocyte functions that are impaired in heart failure, which might improve the heart’s ability to contract. Preclinical studies have found that cimaglermin improved contractile function and possibly protected the heart structure from acute and chronic stressors.
Stroke/Peripheral Nerve Damage
Neuregulins have also demonstrated a range of effects in neuroprotection and repair in preclinical models of disease and injury to both the central and peripheral nervous systems.
In preclinical studies, cimaglermin has been found to partially protect the brain from the consequences of stroke and enhance recovery of sensorimotor function with a wide treatment time window of several days. Preclinical studies have also found improvements in function following damage to peripheral nerves. In a preclinical model that simulates nerve damage that occurs with surgical prostatectomy, cimaglermin was found to protect nerves and restore erectile function.