BACKGROUND: Patients experiencing disuse atrophy report acute loss of skeletal 
muscle mass which subsequently leads to loss of strength and physical capacity. 
In such patients, especially the elderly, complete recovery remains a challenge 
even with improved nutrition and resistance exercise. This study aimed to 
explore the clinical potential of bimagrumab, a human monoclonal antibody 
targeting the activin type II receptor, for the recovery of skeletal muscle 
volume from disuse atrophy using an experimental model of lower extremity 
immobilization.
METHODS: In this double-blind, placebo-controlled trial, healthy young men 
(n = 24; mean age, 24.1 years) were placed in a full-length cast of one of the 
lower extremities for 2 weeks to induce disuse atrophy. After cast removal, 
subjects were randomized to receive a single intravenous (i.v.) dose of either 
bimagrumab 30 mg/kg (n = 15) or placebo (n = 9) and were followed for 12 weeks. 
Changes in thigh muscle volume (TMV) and inter-muscular adipose tissue (IMAT) 
and subcutaneous adipose tissue (SCAT) of the thigh, maximum voluntary knee 
extension strength, and safety were assessed throughout the 12 week study.
RESULTS: Casting resulted in an average TMV loss of -4.8% and comparable 
increases in IMAT and SCAT volumes. Bimagrumab 30 mg/kg i.v. resulted in a rapid 
increase in TMV at 2 weeks following cast removal and a +5.1% increase above 
pre-cast levels at 12 weeks. In comparison, TMV returned to pre-cast level at 
12 weeks (-0.1%) in the placebo group. The increased adiposity of the casted leg 
was sustained in the placebo group and decreased substantially in the bimagrumab 
group at Week 12 (IMAT: -6.6%, SCAT: -3.5%). Knee extension strength decreased 
by ~25% in the casted leg for all subjects and returned to pre-cast levels 
within 6 weeks after cast removal in both treatment arms. Bimagrumab was well 
tolerated with no serious or severe adverse events reported during the study.
CONCLUSIONS: A single dose of bimagrumab 30 mg/kg i.v. safely accelerated the 
recovery of TMV and reversal of accumulated IMAT following 2 weeks in a 
joint-immobilizing cast.