ACE-031 was well tolerated at all dose levels and demonstrated a linear pharmacokinetic profile with an average half-life ranging from 10-15 days Single doses of ACE-031 at 1 mg/kg and 3 mg/kg produced dose-dependent increases in lean body mass measured by dual energy X-ray absorptiometry (DXA) as early as day 15 that were sustained through day 57 Subjects given single doses of placebo had a 0.2% decrease in lean body mass at day 57 compared to a 2.4% increase in subjects receiving 1 mg/kg ACE-031 and a 2.6% increase in subjects receiving 3 mg/kg ACE-031 Subjects given single doses of placebo had a 0.2% decrease in muscle volume assessed by MRI at day 29 compared to a 3.5% increase in subjects receiving 1 mg/kg ACE-031 and 5% increase in subjects receiving 3 mg/kg ACE-031 ACE-031 favorably affected biomarkers of fat mass (increased adiponectin and decreased leptin) and bone formation and resorption (increased bone-specific alkaline phosphatase (BSAP) and decreased C-terminal type 1 collagen telopeptide (CTX)) at doses of 1 and 3 mg/kg
ACE-031 holds great potential as a treatment for patients suffering from neuromuscular diseases such as muscular dystrophy and amyotrophic lateral sclerosis (ALS), said John Knopf, Ph.D., Chief Executive Officer of Acceleron. We are moving forward with great confidence and excitement with the ACE-031 program as well as our overall muscle franchise.
Muscle is increasingly recognized as central to many biological processes and plays a major role in human health. The loss of muscle mass and strength is ultimately directly related to the cause of death in neuromuscular diseases such as muscular dystrophy and amyotrophic lateral sclerosis. Severe muscle loss in cancer leads to serious complications and a poor prognosis. Muscle loss is a natural consequence of aging, similar to bone loss, resulting in decreased muscle strength (frailty), reduced mobility and an increased risk of a fall and broken bones. In metabolic diseases, an imbalance of diet, energy utilization and skeletal muscle leads to poor metabolic function. By increasing muscle mass there is a corresponding decrease in fat mass and improvements in metabolic function.
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