Treatment of Sarcopenia with Bimagrumab: Results from a Phase II, Randomized, Controlled, Proof-of-Concept Study

Abstract

Objectives: To assess the effects of bimagrumab on skeletal muscle mass and function in older adults with sarcopenia and mobility limitations.

Design: A 24-week, randomized, double-blind, placebo-controlled, parallel-arm, proof-of-concept study.

Setting: Five centers in the United States.

Participants: Community-dwelling adults (N = 40) aged 65 and older with gait speed between 0.4 and 1.0 m/s over 4 m and an appendicular skeletal muscle index of 7.25 kg/m² or less for men and 5.67 kg/m² or less for women.

Intervention: Intravenous bimagrumab 30 mg/kg (n = 19) or placebo (n = 21).

Measurements: Change from baseline in thigh muscle volume (TMV), subcutaneous and intermuscular fat, appendicular and total lean body mass, grip strength, gait speed, and 6-minute walk distance (6MWD).

Results: Thirty-two (80%) participants completed the study. TMV increased by Week 2, was sustained throughout the treatment period, and remained above baseline at the end of study in bimagrumab-treated participants, whereas there was no change with placebo treatment (Week 2: 5.15 ± 2.19% vs -0.34 ± 2.59%, P < .001; Week 4: 6.12 ± 2.56% vs 0.16 ± 3.42%, P < .001; Week 8: 8.01 ± 3.70% vs 0.35 ± 3.32%, P < .001; Week 16: 7.72 ± 5.31% vs 0.42 ± 5.14%, P < .001; Week 24: 4.80 ± 5.81% vs -1.01 ± 4.43%, P = .002). Participants with slower walking speed at baseline receiving bimagrumab had clinically meaningful and statistically significantly greater improvements in gait speed (mean 0.15 m/s, P = .009) and 6MWD (mean 82 m, P = .022) than those receiving placebo at Week 16. Adverse events in the bimagrumab group included muscle-related symptoms, acne, and diarrhea, most of which were mild in severity and resolved by the end of study.

Conclusion: Treatment with bimagrumab over 16 weeks increased muscle mass and strength in older adults with sarcopenia and improved mobility in those with slow walking speed.

Keywords: 6-minute walk test; bimagrumab; gait speed; lean body mass; muscle; randomized controlled trial; sarcopenia.