RESILIENT: A Randomized, Double-Blind, Placebo-Controlled Study of Bimagrumab in Patients With Sporadic Inclusion Body Myositis (P1.111)

Objective: To examine efficacy and safety of bimagrumab (BYM338)in patients with sporadic inclusion body myositis (sIBM) measured by physical function, muscle strength, and muscle mass. Background: Bimagrumab is a novel fully human monoclonal antibody that binds competitively to activin type II receptors with greater affinity than natural ligands which limit muscle mass growth, including activin and myostatin. Design/Methods: RESILIENT was a multicenter, randomized, double-blind, placebo-controlled, dose-finding study (ClinicalTrials.govidentifier: NCT01925209). Eligible participants were randomized (1:1:1:1) to receive i.v. infusions of bimagrumab 10, 3, 1 mg/kg or placebo every 4 weeks for at least 48 weeks (for 52 weeks of exposure). Efficacy was assessed at Week52 by the 6-Minute Walking Distance (6MWD) test, a patient-reported outcome using the Sporadic Inclusion Body Myositis Functional Assessment (sIFA), and by other muscle strength measurements. Results: 251 patients were randomized and treated. There were no statistically significant differences between placebo and any of the three bimagrumab dose groups in the change from baseline of the 6MWD test at Week 52 ( p >0.1). However, bimagrumab 10 mg/kg demonstrated a statistically significant difference versus placebo ( p =0.03) in change from baseline of the sIFA total score, whereas the two lower doses showed a positive numerical trend compared with placebo at Week 52. The most frequently reported AEs in the bimagrumab groups were muscle spasm and diarrhea. However, no findings suggestive of cardiac effects on cardiac heart muscle or its contractility on electrocardiogram were reported. Conclusions: Bimagrumab was generally safe and well-tolerated in the sIBM patient population. The results from this phase IIb/III study showed that at Week 52 self-reported physical functioning (measured by sIFA)was significantly better preserved compared to baseline in patients treated with bimagrumab 10 mg/kg versus placebo. The study did not, however, reach the primary endpoint of improving the 6MWD or show an improvement in muscle strength. Study Supported by: Study Supported by Novartis Pharma AG. Disclosure: Dr. Amato has received person compensation from Novartis and Idera as an advisory board member. Dr. Badrising9s institution (The LUMC) received compensation for consultancy and clinical trial fees from Novartis and consultancy compensation from Argen X for work done by U.B. Dr. Benveniste has received personal compensation for activities with Shire, LFB, Novartis, CSL Behring, and Neovacs, Dr. Benveniste has received research support from Novartis and Neovacs. Dr. Needham has received personal compensation for activities with Novartis, Biogen, and Bayer. Dr. Chinoy has received personal compensation for activities with Novartis – and UCB as a speaker and/or advisory board member. Dr. Wu has received personal compensation for activities with Novartis. Dr. Koumaras has received personal compensation for activities with Novartis. Dr. Koumaras has received personal compensation in an editorial capacity for Novartis. Dr. de Vera has received personal compensation for activities with Novartis Pharma AG as an employee. Dr. Papanicolaou has received personal compensation for activities with Novartis Pharmaceuticals as an employee. Dr. Hanna has received personal compensation for activities with Novartis as a consultant. Dr. Hanna has received research support from MRC Centre.