Journal
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
Volume 199, Issue 3, Pages 313-320Publisher
AMER THORACIC SOC
DOI: 10.1164/rccm.201802-0286OC
Keywords
bimagrumab; thigh muscle volume; 6-minute-walk distance; lean body mass
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Funding
- Novartis Institutes for BioMedical Research
- National Institute for Health Research Respiratory Biomedical Research Unit at the Royal Brompton and Harefield National Health Service Foundation Trust and Imperial College, London, UK
- MRC [G1001362, G0501985] Funding Source: UKRI
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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/m(2) or appendicular skeletal muscle mass index <= 7.25 [men] and <= 5.67 [women] kg/m(2)), 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.
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