Hanna MG, Badrising UA, Benveniste O, Lloyd TE, Needham M, Chinoy H, Aoki M, Machado PM, Liang C, Reardon KA, de Visser M, Ascherman DP, Barohn RJ, Dimachkie MM, Miller JAL, Kissel JT, Joyce NC, Van den Bergh P, Baets J, De Bleecker JL, Karam C, David WS, Mirabella M, Nations SP, Jung HH, Pegoraro E, Maggi L, Rodolico C, Filosto M, Shaibani AL, Sivakumar K, Goyal NA, Mori-Yoshimura M, Yamashita S, Suzuki N, Katsuno M, Murata K, Nodera H, Nishino I, Romano C, Williams VSL, Vissing J, Zhang Auberson L, Wu M, de Vera A, Papanicolaou DA, Amato AA, RESILIENT Study Group. Safety and efficacy of intravenous bimagrumab in inclusion body myositis: a phase 2b, randomised, double-blind, placebo-controlled study (RESILIENT). Lancet Neurol. 2019 Apr 12.

BACKGROUND: To assess the efficacy, safety, and tolerability of bimagrumab (fully human monoclonal antibody) in participants with inclusion body myositis (IBM).

METHODS: This multicentre, double-blind, placebo-controlled study (RESILIENT; ClinicalTrials.gov, number NCT01925209) was conducted between September 26, 2013 and January 06, 2016 at academic clinical sites in Europe, the USA, Australia, and Japan. Eligible participants (aged 36–85 years [inclusive]; modified 2010 MRC criteria) were randomly assigned (1:1:1:1) using blocked randomisation schedule (block size=4) to receive intravenous infusions of bimagrumab 10, 3, 1 mg/kg, or placebo every 4 weeks for at least 48 weeks. All study participants, sponsor, investigators, site personnel, and those performing assessments were masked to treatment assignment. 6-minute walking distance (6MWD; primary outcome measure) was assessed at Week 52 in the primary analysis population. A multivariate normal repeated measures model was used to analyse data on 6MWD. Safety was assessed by recording adverse events (AEs), electrocardiography, echocardiography, hematology, urinalysis, and blood chemistry.

FINDINGS: At Week 52, there were no statistically significant differences in 6MWD change from baseline for any of the bimagrumab groups (10, 3, 1 mg/kg) versus placebo (least squares mean treatment difference (SE;99%CI): 17·6 m (14·3;19·6,54·8) p=0·2210, 18·6 m (14·2;18·2,55·4) p=0·1909, and 1·3 m (14·1;38·0,35·4) p=0·9263, respectively). There were 63(100%) participants in each bimagrumab group and 61(98.4%) in the placebo group who experienced at least one AE. Proportion of participates reporting at least serious AE was 21(33·3%), 11(17·5%), 20(31·7%), and 20(32·3%) in the respective groups. No significant adverse cardiac effects were observed on electrocardiography or echocardiography testing.

Bimagrumab demonstrated a good safety profile in the IBM population but did not improve 6MWD. Strengths of the study are that it is the largest RCT conducted in IBM and provides important natural history data over 12 months.

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