Long-term safety and tolerability of bimagrumab (BYM338) in sporadic inclusion body myositis

Objective: To assess the long-term safety, tolerability and monitor benefits of extended use of bimagrumab in individuals with sporadic inclusion body myositis (sIBM) who completed a single-dose core study.

Methods: In this multicenter, open-label extension study, 10 adults received bimagrumab 10 mg/kg IV every 4 weeks up to 2 years (104 weeks). Safety (primary endpoint) was assessed by recording adverse events (AEs). Clinical benefits were assessed by changes from baseline in thigh muscle volume (TMV), lean body mass (LBM), 6-minute walk distance (6MWD), handgrip and quadriceps strength.

Results: Participants had a mean (standard deviation [SD]) age of 70.1 (10.4) years. All participants (n = 10) discontinued the treatment due to early termination of the study (n = 7) or AEs (n = 3; myocardial infarction, esophageal carcinoma, and dementia, none of which were treatment-related). The most common AEs were muscle spasms and falls (both 9/10, 90%), followed by diarrhea (6/10, 60%), acne and skin eruption (both 5/10, 50%). At weeks 8 and 16, mean (SD) TMV increased from baseline by 4.1% (4.3) and 4.5% (6.3). Mean LBM increased from baseline and was sustained at 6.9% (3.9) at week 76. Means of 6MWD showed a progressive decline from baseline to week 76, during which there was a modest numerical increase in handgrip strength and no significant changes in quadriceps strength.

Conclusions: Long-term treatment up to 2 years with bimagrumab had good safety profile and was well-tolerated in individuals with sIBM. An increase in muscle mass was noted on a group level, however, there was no evidence of clinical improvement.

Classification of evidence: This study provides Class IV evidence that for patients with sIBM, long-term bimagrumab treatment was safe and well-tolerated and did not lead to functional improvement.