Pharmacologic Inhibition of Myostatin and Changes in Lean Body Mass and Lower Extremity Muscle Size in Patients Receiving Androgen Deprivation Therapy for Prostate Cancer.

Publication Type:

Journal Article

Source:

The Journal of clinical endocrinology and metabolism, p.jc20141271 (2014)

Keywords:

2014, Clinical Research Division, July 2014

Abstract:

Context: Myostatin is a negative regulator of muscle growth. Androgen deprivation (ADT) is associated with muscle loss and increased body fat and currently available therapies have limited efficacy to treat this complication. The anti-myostatin peptibody (AMG 745/Mu-S) markedly attenuated muscle loss and decreased fat accumulation in orchiectomized mice. Objective: The objective was to evaluate safety, pharmacokinetics (PK) and muscle efficacy of AMG 745 in men undergoing ADT for non-metastatic prostate cancer. Methods: This was a randomized, blinded, placebo-controlled multiple dose phase 1 study of AMG 745 given for 28 days. The endpoint of percent change from baseline in lean body mass (LBM) as assessed by dual x-ray absorptiometry (DXA) was pre-specified. Results: Rates of adverse events (AMG 745 versus placebo) were: diarrhea (13% versus 9%), fatigue (13% versus 4%), contusion (10% versus 0%), and injection site bruising (6% versus 4%). Exposure increased linearly from 0.3 mg/kg to 3 mg/kg. AMG 745 significantly increased LBM in the 3 mg/kg versus placebo groups on Day 29 by 2.2% (± 0.8% standard error [SE]), p = 0.008; in exploratory fat mass analysis, a decrease - 2.5% (± 1.0% SE), p = 0.021 was observed. Pharmacodynamic changes in muscle and fat were maintained at follow-up, 1 month after Day 29. Conclusion: Four weekly SC doses of AMG 745 were well tolerated and were associated with increased LBM and decreased fat in the men receiving ADT for non-metastatic prostate cancer. Results support further investigation of AMG 745 in clinical settings with muscle loss and atrophy.