Efficacy and Safety of Bimagrumab in Sporadic Inclusion Body Myositis
Anthony A. Amato, Michael G. Hanna, Pedro Machado, Umesh A. Badrising, Hector Chinoy, Olivier Benvéniste, Ananda Krishna Karanam, Min Wu, László B. Tankó, Agnes Annette Schubert-Tennigkeit, Dimitris A. Papanicolaou, Thomas E. Lloyd, Merrilee Needham, Christina Liang, Katrina Reardon, Marianne de Visser, Dana P. Ascherman, Richard J. Barohn, Mazen M. Dimachkie, James Miller, John T. Kissel, Björn Oskarsson, Nanette C. Joyce, Peter Van den Bergh, Jonathan Baets, Jan De Bleecker, Chafic Karam, William S. David, Massimiliano Mirabella, Sharon Nations, Hans H. Jung, Elena Pegoraro, Lorenzo Maggi, Carmelo Rodolico, Massimiliano Filosto, Aziz Shaibani, Kumaraswamy Sivakumar, Namita Goyal, Madoka Mori‐Yoshimura, Satoshi Yamashita, Naoki Suzuki, Masashi Aoki, Masahisa Katsuno, Hirokazu Morihata, Kenya Murata, Hiroyuki Nodera, Ichizo Nishino, Carla DeMuro, Valerie Williams, John Vissing, Lixin Zhang Auberson, on behalf of the RESILIENT Study Extension Group, Susan Walters, Dave Hathorn, Sam Salman, Melanie Burk, Ruby Chen, Mary Jenkins, Carolyn M. Sue, Susan Mathers, Ruth Krasniqi, Lisa Mottram, Katie Fitzgerald, James R. Howe, Hanne Files, Ruby Chen, Linda Wagemaekers, Peter De Jonghe, Délphine Mahieu, Tom Heremans, Kathy de Koning, Katrien De Mey, Stefanie Cardoen, Chantal Miclotte, Marie-Odile Bioul, Anne Mette Ostergaard Autzen, Julia R. Dahlqvist, Martin Jorsal, Nanna Witting, Jane Pedersen, K. Knak, Linda Andersen, Maj-Brit Tanderup Joergensen, J. Hogrel, Laurent Gilardin, G. Ollivier, N. Champtiaux, V. Decostre, Aude Rigolet, C. Lilien, Yves Allenbach, Anne Simon, Damien Bachasson, Chiara De Fino, Matteo Lucchini, Assunta Bianco, Francesco Antonio Losavio, Luca Bello, Ilaria Martinelli, Claudio Semplicini
Abstract
OBJECTIVE: To assess long-term (2 years) effects of bimagrumab in participants with sporadic inclusion body myositis (sIBM). METHODS: Participants (aged 36-85 years) who completed the core study (RESILIENT [Efficacy and Safety of Bimagrumab/BYM338 at 52 Weeks on Physical Function, Muscle Strength, Mobility in sIBM Patients]) were invited to join an extension study. Individuals continued on the same treatment as in the core study (10 mg/kg, 3 mg/kg, 1 mg/kg bimagrumab or matching placebo administered as IV infusions every 4 weeks). The co-primary outcome measures were 6-minute walk distance (6MWD) and safety. RESULTS: Between November 2015 and February 2017, 211 participants entered double-blind placebo-controlled period of the extension study. Mean change in 6MWD from baseline was highly variable across treatment groups, but indicated progressive deterioration from weeks 24-104 in all treatment groups. Overall, 91.0% (n = 142) of participants in the pooled bimagrumab group and 89.1% (n = 49) in the placebo group had ≥1 treatment-emergent adverse event (AE). Falls were slightly higher in the bimagrumab 3 mg/kg group vs 10 mg/kg, 1 mg/kg, and placebo groups (69.2% [n = 36 of 52] vs 56.6% [n = 30 of 53], 58.8% [n = 30 of 51], and 61.8% [n = 34 of 55], respectively). The most frequently reported AEs in the pooled bimagrumab group were diarrhea 14.7% (n = 23), involuntary muscle contractions 9.6% (n = 15), and rash 5.1% (n = 8). Incidence of serious AEs was comparable between the pooled bimagrumab and the placebo group (18.6% [n = 29] vs 14.5% [n = 8], respectively). CONCLUSION: Extended treatment with bimagrumab up to 2 years produced a good safety profile and was well-tolerated, but did not provide clinical benefits in terms of improvement in mobility. The extension study was terminated early due to core study not meeting its primary endpoint. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT02573467. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for patients with sIBM, long-term treatment with bimagrumab was safe, well-tolerated, and did not provide meaningful functional benefit. The study is rated Class IV because of the open-label design of extension treatment period 2.