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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.
Glossary
- 6MWD=
- 6-minute walk distance;
- ActRII=
- activin type II receptors;
- AE=
- adverse event;
- AESI=
- adverse event of special interest;
- DEXA=
- dual-energy X-ray absorptiometry;
- DMC=
- data monitoring committee;
- FAS=
- full analysis set;
- LBM=
- lean body mass;
- MedDRA=
- Medical Dictionary for Regulatory Activities;
- QMT=
- quantitative muscle testing;
- RESILIENT=
- Efficacy and Safety of Bimagrumab/BYM338 at 52 Weeks on Physical Function, Muscle Strength, Mobility in sIBM Patients;
- SAE=
- serious adverse event;
- sIBM=
- sporadic inclusion body myositis;
- sIFA=
- sporadic inclusion body myositis functional assessment;
- SPPB=
- Short Physical Performance Battery
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
RESILIENT Study Extension Group members are listed in the appendix 2 at the end of article.
Editorial, page 555
Class of Evidence: NPub.org/coe
Podcast: NPub.org/uias4v
- Received August 12, 2020.
- Accepted in final form December 10, 2020.
- © 2021 American Academy of Neurology
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