Efficacy and Safety of Bimagrumab in Sporadic Inclusion Body Myositis: Long-term Extension of RESILIENT

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.

Figure 1. Study Design and Participant Disposition

(A) Study design. (B) Participant disposition in the extension study during double-blind extension treatment period 1 (excluding follow-up period) (full analysis set). Maximum duration of extension treatment period was 52 weeks.

Figure 2. Mean Change From Core Baseline in 6-Minute Walk Distance (6MWD) During Double-Blind Treatment

Error bars represent SEM. At each visit, only participants with a value at both core baseline and the post core baseline visit were included. Number of participants contributing to the data analyzed for means of 6MWD at week 104 was considerably lower than earlier visits. Baseline was defined as the last assessment before the first dose of core study drug. All participants were included regardless of intervening drug holiday. Treatment for participants in the double-blind period of the extension study was stopped as the core study (RESILIENT [Efficacy and Safety of Bimagrumab/BYM338 at 52 Weeks on Physical Function, Muscle Strength, Mobility in sIBM Patients]) did not meet the primary endpoint, and all participants were switched to a 6-month off-drug follow-up period.

Figure 3. Mean Change From Core Baseline in Sporadic Inclusion Body Myositis Functional Assessment (sIFA) Total Score During Double-Blind Treatment

Error bars represent SEM. The number of participants contributing to the means analyzed for sIFA total scores across all treatment groups at week 104 decreased by 13–15 due to early termination of study medication in the extension study. sIFA total score is between 0 and 100 with 0 indicating no difficulties. Baseline is defined as the last assessment before the first dose of study drug. Results from tests performed more than 56 days after discontinuation of study drug are not shown. All participants were included regardless of any drug holiday. sIFA items are rated on an 11-point numerical rating scale from 0 (no difficulty) to 10 (unable to do) across 3 domains: upper body functioning (e.g., “carry a 5-pound object”), lower body functioning (e.g., “step up and down sidewalk or street curbs”), and general functioning (e.g., “get on and off a toilet”).

Figure 4. Mean Change From Core Baseline in Quantitative Muscle Testing (QMT) of the Right Quadriceps Muscle During the Double-Blind Treatment Period

Error bars represent SEM. At each visit, only participants with a value at both core baseline and the post core baseline visit were included. Baseline is defined as the last assessment before the first dose of core study drug. All participants were included regardless of any drug holiday.

Figure 5. Mean Change From Core Baseline in Right Handgrip Strength During Double-Blind Treatment

Error bars represent SEM. At each visit, only participants with a value at both core baseline and the post core baseline visit were included. Baseline is defined as the last assessment before the first dose of core study drug. All participants were included regardless of their drug holiday.