Activin Type II Receptor Blockade for Treatment of Muscle Depletion in Chronic Obstructive Pulmonary Disease. A Randomized Trial

• Published in: American journal of respiratory and critical care medicine Vol. 199; no. 3; pp. 313 - 320
• Main Authors: Polkey, Michael I, Praestgaard, Jens, Berwick, Amy, Franssen, Frits M E, Singh, Dave, Steiner, Michael C, Casaburi, Richard, Tillmann, Hanns-Christian, Lach-Trifilieff, Estelle, Roubenoff, Ronenn, Rooks, Daniel S
• Format: Journal Article
• Language: English
• Published: United States American Thoracic Society 01-02-2019
• Subjects: Activin Receptors - antagonists & inhibitors; Adult; Aged; Aged, 80 and over; Antibodies, Blocking - therapeutic use; Antibodies, Monoclonal - therapeutic use; Antibodies, Monoclonal, Humanized; Biomarkers; Body Composition - drug effects; Body mass index; Chronic obstructive pulmonary disease; Clinical trials; Double-Blind Method; Evidence-based medicine; Female; Humans; Male; Middle Aged; Mortality; Muscle function; Muscle, Skeletal - drug effects; Muscular Atrophy - etiology; Muscular Atrophy - prevention & control; Musculoskeletal system; Original; Pulmonary Disease, Chronic Obstructive - complications; Rehabilitation; Thigh; lean body mass; thigh muscle volume; bimagrumab; 6-minute-walk distance
• ISSN: 1073-449X; 1535-4970; 1535-4970
• DOI: 10.1164/rccm.201802-0286OC

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.
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.
Sixty-seven patients with COPD (mean FEV
, 1.05 L [41.6% predicted]; aged 40-80 yr; body mass index < 20 kg/m
or appendicular skeletal muscle mass index ≤ 7.25 [men] and ≤ 5.67 [women] kg/m
), received two doses of either bimagrumab 30 mg/kg intravenously (n = 33) or placebo (n = 34) (Weeks 0 and 8) over 24 weeks.
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.
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).