Session Type: ACR Late-breaking Abstract Session
Session Time: 9:00AM-11:00AM
Background/Purpose: Bimagrumab (BYM338) is a novel fully human monoclonal antibody that binds competitively to activin type II receptors with greater affinity than natural inhibitory ligands such as activin and myostatin, thereby inducing skeletal muscle hypertrophy. This study examined efficacy and safety of bimagrumab on physical function, muscle strength and muscle mass in patients with sporadic inclusion body myositis (sIBM).
Methods: RESILIENT was a multicenter, randomized, double-blind, placebo-controlled, dose-finding study (clinicaltrials.gov 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. Change from baseline to Week 52 in 6-minute walk distance test (6MWD; primary outcome), quadriceps quantitative muscle testing (QMT), sIBM physical functioning assessment (sIFA) and lean body mass (LBM) were assessed. Safety assessments included recording of adverse events (AEs) and serious AEs.
Results: 251 patients (mean[SD] age: 68.1[8.2] years; 162[64.5%] men; mean time since sIBM diagnosis: 4.6[3.53] years) were randomized and treated. Participants on placebo and 1 mg/kg bimagrumab had a mean 6MWD decrease from baseline to Week 52 of 8.96 and 10.27 m, respectively, vs. an increase of 9.63 m for 3 mg/kg and 8.63 m for 10 mg/kg bimagrumab. Differences between treatment vs. placebo did not reach statistical significance (p>0.1). No consistent differences in quadriceps QMT were observed vs. placebo. However, at Week 52, there was less deterioration (mean treatment difference: 5.10; 0-100 scale) in the patient-reported outcome (PRO) instrument, sIFA, in 10 mg/kg bimagrumab vs. placebo (p=0.03), resulting in a clinically relevant and statistically significant increase in responders in this group (55% vs. 30%; p=0.0115). Bimagrumab showed a dose-dependent increase in LBM vs. placebo (mean treatment ratios: 3 and 10 mg/kg vs. placebo: 1.033 and 1.058, respectively). At Week 52, the difference was statistically significant for the 3 and 10 mg/kg doses (p≤0.0001). The most frequently reported AEs in the bimagrumab groups were diarrhea and muscle spasm. About one-third patients in all groups reported serious AEs, except for bimagrumab 3 mg/kg (17.5%).
Conclusion: Bimagrumab was well-tolerated, increased LBM and showed a potential benefit in PRO, but did not reach the primary endpoint of improving 6MWD or showed an improvement in muscle strength.
Disclosure: A. A. Amato, Novartis, Acceleron, Biogen, Idera, Akashi, 5; U. Badrising, Novartis, 5; O. Benveniste, Shine, LFB, Novartis, CSL Behring, 2,Novartis, Neovacs, 5; M. Needham, Biogen, Bayer, Novartis, 5; H. Chinoy, MedImmune, Abbvie, Novartis, 2,Abbvie, Celgene, Johnson & Johnson, Pfizer, Roche, UCB, 5; M. Wu, Novartis Pharmaceuticals Corporation, 3; B. Koumaras, Novartis Pharmaceuticals Corporation, 3; A. de Vera, Novartis Pharma AG, 3; D. A. Papanicolaou, Novartis Pharmaceuticals Corporation, 3; M. G. Hanna, Novartis, 5.
To cite this abstract in AMA style:Amato AA, Badrising U, Benveniste O, Needham M, Chinoy H, Wu M, Koumaras B, de Vera A, Papanicolaou DA, Hanna MG. A Randomized, Double-Blind, Placebo-Controlled Study of Bimagrumab in Patients with Sporadic Inclusion Body Myositis [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). http://acrabstracts.org/abstract/a-randomized-double-blind-placebo-controlled-study-of-bimagrumab-in-patients-with-sporadic-inclusion-body-myositis/. Accessed September 21, 2017.
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