Bimagrumab vs Optimized Standard of Care for Treatment of Sarcopenia in Community-Dwelling Older Adults: A Randomized Clinical Trial

Abstract

Importance: The potential benefit of novel skeletal muscle anabolic agents to improve physical function in people with sarcopenia and other muscle wasting diseases is unknown.

Objective: To confirm the safety and efficacy of bimagrumab plus the new standard of care on skeletal muscle mass, strength, and physical function compared with standard of care alone in community-dwelling older adults with sarcopenia.

Design, setting, and participants: This double-blind, placebo-controlled, randomized clinical trial was conducted at 38 sites in 13 countries among community-dwelling men and women aged 70 years and older meeting gait speed and skeletal muscle criteria for sarcopenia. The study was conducted from December 2014 to June 2018, and analyses were conducted from August to November 2018.

Interventions: Bimagrumab 700 mg or placebo monthly for 6 months with adequate diet and home-based exercise.

Main outcomes and measures: The primary outcome was the change in Short Physical Performance Battery (SPPB) score after 24 weeks of treatment. Secondary outcomes included 6-minute walk distance, usual gait speed, handgrip strength, lean body mass, fat body mass, and standard safety parameters.

Results: A total of 180 participants were recruited, with 113 randomized to bimagrumab and 67 randomized to placebo. Among these, 159 participants (88.3%; mean [SD] age, 79.1 [5.3] years; 109 [60.6%] women) completed the study. The mean SPPB score increased by a mean of 1.34 (95% CI, 0.90 to 1.77) with bimagrumab vs 1.03 (95% CI, 0.53 to 1.52) with placebo (P = .13); 6-minute walk distance increased by a mean of 24.60 (95% CI, 7.65 to 41.56) m with bimagrumab vs 14.30 (95% CI, -4.64 to 33.23) m with placebo (P = .16); and gait speed increased by a mean of 0.14 (95% CI, 0.09 to 0.18) m/s with bimagrumab vs 0.11 (95% CI, 0.05 to 0.16) m/s with placebo (P = .16). Bimagrumab was safe and well-tolerated and increased lean body mass by 7% (95% CI, 6% to 8%) vs 1% (95% CI, 0% to 2%) with placebo, resulting in difference of 6% (95% CI, 4% to 7%) (P < .001).

Conclusions and relevance: This randomized clinical trial found no significant difference between participants treated with bimagrumab vs placebo among older adults with sarcopenia who had 6 months of adequate nutrition and light exercise, with physical function improving in both groups. Bimagrumab treatment was safe, well-tolerated, increased lean body mass, and decreased fat body mass. The effects of sarcopenia, an increasing cause of disability in older adults, can be reduced with proper diet and exercise.

Trial registration: ClinicalTrials.gov Identifier: NCT02333331; EudraCT number: 2014-003482-25.

Conflict of interest statement

Conflict of Interest Disclosures: Drs Rooks, Swan, Filosa, Mr Bunte, Drs Panchaud, Coleman, Miller, Garcia Garayoa, Praestgaard, Laurent, and Petricoul, Ms Hemsley, Drs Lach-Trifilieff, Papanicolaou, and Roubenoff are employees of Novartis and may be eligible for Novartis stock and stock options. Dr Rooks reported having a patent for use of bimagrumab in sarcopenia pending. Dr Coleman had a patent for PAT058683 pending. Dr Fogarty reported receiving grants from Novartis during the conduct of the study. Dr Lach-Trifilieff reported having a patent for WO2010/125003 pending, a patent for US13/485399 issued, a patent for US14/806997 pending, a patent for US15/906703 pending, and a patent for US12/767509 issued. Dr Roubenoff reported having a patent for bimagrumab issued for Novartis. No other disclosures were reported.

Figures

Figure 1.. Study Flow Diagram of Participant Screening and Enrollment

AE indicates adverse events; PD, pharmacodynamics; and PK, pharmacokinetics.

Figure 2.. Effect of Bimagrumab Compared With Placebo on Physical Performance Assessed

A repeated measure mixed model with a covariate for treatment (placebo or bimagrumab), visit, baseline, visit × baseline, visit × treatment, and region (Asian and non-Asian) was used. No adjustment for multiplicity was made. The baseline value considered for the calculation of the change from baseline is the last value before Day 1.