RATIONALE: Bimagrumab is a fully human monoclonal antibody that blocks the 
activin type II receptors, preventing the activity of myostatin and other 
negative skeletal muscle regulators.
OBJECTIVES: To assess the effects of bimagrumab on skeletal muscle mass and 
function in patients with chronic obstructive pulmonary disease (COPD) and 
reduced skeletal muscle mass.
METHODS: Sixty-seven patients with COPD (mean FEV1, 1.05 L [41.6% predicted]; 
aged 40-80 yr; body mass index < 20 kg/m2 or appendicular skeletal muscle mass 
index ≤ 7.25 [men] and ≤ 5.67 [women] kg/m2), received two doses of either 
bimagrumab 30 mg/kg intravenously (n = 33) or placebo (n = 34) (Weeks 0 and 8) 
over 24 weeks.
MEASUREMENTS AND MAIN RESULTS: We assessed changes in thigh muscle volume (cubic 
centimeters) as the primary endpoint along with 6-minute-walk distance (meters), 
safety, and tolerability. Fifty-five (82.1%) patients completed the study. Thigh 
muscle volume increased by Week 4 and remained increased at Week 24 in 
bimagrumab-treated patients, whereas no changes were observed with placebo (Week 
4: +5.9% [SD, 3.4%] vs. 0.0% [3.3%], P < 0.001; Week 8: +7.0% [3.7%] vs. -0.7% 
[2.8%], P < 0.001; Week 16: +7.8% [5.1%] vs. -0.9% [4.5%], P < 0.001; Week 24: 
+5.0% [4.9%] vs. -1.3% [4.3%], P < 0.001). Over 24 weeks, 6-minute-walk distance 
did not increase significantly in either group. Adverse events in the bimagrumab 
group included muscle-related symptoms, diarrhea, and acne, most of which were 
mild in severity.
CONCLUSIONS: Blocking the action of negative muscle regulators through the 
activin type II receptors with bimagrumab treatment safely increased skeletal 
muscle mass but did not improve functional capacity in patients with COPD and 
low muscle mass. Clinical trial registered with www.clinicaltrials.gov 
(NCT01669174).