Long-Term Efficacy and Safety of Bimagrumab in Inclusion Body Myositis: 2 Years Results (S38.003)

Objective: RESILIENT study extension (N=211) (ClinicalTrials.gov Identifier: NCT02573467) further assessed long-term efficacy and safety of bimagrumab in participants with inclusion body myositis (IBM) beyond 12-month treatment. Background: RESILIENT is the largest Phase III clinical study (core; N=251) in IBM. RESILIENT study(ClinicalTrials.gov number, NCT01925209) showed that at Week 52 bimagrumab increased lean body mass and improved function on sporadic IBM functional assessment (sIFA) scale, but did not reach the primary endpoint of improving 6-minute walk test (6MWT) or showed an improvement in muscle strength. Design/Methods: During double-blind treatment in the extension, participants continued study drug they were randomized to in the core study (bimagrumab 10, 3, 1 mg/kg or placebo every 4 weeks). Participants were switched to 6-month post-treatment follow-up after ending the extension phase. Outcome measures included 6MWT, sIFA and muscle strength measurements. Safety assessments included reporting of adverse events (AEs) and serious AEs. Results: Beyond Week 52, mean change in 6MWT showed highly variable but progressive decline to Week 104 in all groups. There was an increased difference in change from core baseline in sIFA total score between 10 mg/kg and placebo from Week 52 to 78 (−1.34[n=53] and 5.16[n=52] vs. −0.27[n=53] and 7.41[n=54], respectively), however, the responses were converging at Week 104 (3.54[n=38] and 7.39[n=40], respectively). Differences in muscle strength per quantitative muscle testing and hand grip between bimagrumab and placebo groups were not clinically meaningful at any time point. The most frequently reported AEs (>5% incidence) in the pooled bimagrumab group were diarrhea (14.7%), muscle spasm (9.6%), and rash (5.1%). Conclusions: Long-term use of bimagrumab was well-tolerated, and continued treatment up to 104 weeks did not result in meaningful functional benefits in the study population. These findings may help to understand the disease course and develop new therapies. Study Supported by: Study Supported by Novartis Pharma AG, Basel, Switzerland Disclosure: Dr. Amato has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Strongbridge Pharmaceuticals. Dr. Zhang-Auberson holds stock and/or stock options in Dr. Auberson is an employee of Novartis and may be eligible for stock and/or stock options in Novartis, which sponsored research in which Dr. Zhang-Auberson was involved as an investigator. Dr. Hanna has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Prof. Hanna has received personal compensation for activities with Novartis as a consultant and he has received research support from the MRC centre grant. Dr. Badrising has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Dr. Badrising’s 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. Needham has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Dr. Needham has received personal compensation for activities with Novartis, Biogen, and Bayer. Dr. Chinoy has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Dr. Chinoy has received personal compensation for activities with Novartis, UCB, Janssen, Lilly as a speaker and/or advisory board member. Dr. Aoki has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Prof. Aoki has received personal compensation for activities with Novartis as a consultant and has received research grants from the Japanese Ministry of Health Labor and Welfare, the Japanese Ministry of Education, Culture, Sports, Science and Technology. Dr. Koumaras has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Barbara Koumaras is an employee of Novartis. Dr. Tanko has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Dr. Tanko is an employee of Novartis. Dr. Wu has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Dr. Wu is an employee of Novartis. Dr. Papanicolaou holds stock and/or stock options in Dr. Papanicolaou is an employee of Novartis and may be eligible for stock and/or stock options in Novartis, which sponsored research in which Dr. Papanicolaou was involved as an investigator. Dr. Benveniste has nothing to disclose.