Overall, 91% of participants in the pooled bimagrumab group and 89.1% in the placebo group had at least 1 or more treatment-emergent adverse event.
Results from the RESILIENT long-term extension study (NCT01925209) showed that treatment with bimagrumab (BYM338; Novartis) produced a good safety profile and was well-tolerated but did not provide clinical benefits in terms of improvement of mobility in patients with sporadic inclusion body myositis (sIBM).1
Researchers used 6-minute walk distance (6MWD) and safety as the co-primary end point outcomes. They found that the mean change in 6MWD from baseline was highly variable across treatment arms and showed progressive decline from week 24 to week 104 in all treatment groups. Notably, this decline followed a small transient increase during the first 6 months of the core study.
Lead author Anthony A Amato, MD, neurologist, Brigham and Women’s Hospital, and professor of neurology, Harvard Medical School, and colleagues terminated the extension study due to the core study not meeting its primary end point of significant change in 6MWD.
The RESILIENT core study was a randomized, double-blind, placebo-controlled, dose-finding, phase 2b study. It was the largest phase 2b clinical study of an activin type 2 receptor antagonist in participants with sIBM. Eligible participants were randomly assigned 1:1:1:1 to receive intravenous (IV) infusions of bimagrumab 10 mg/kg, 3 mg/kg, 1 mg/kg, or matching placebo every 4 weeks.
Bimagrumab, a monoclonal antibody developed to treat pathological muscle loss and weakness, led to at least 1 treatment-emergent adverse event (TEAE) in 91% (n = 142) of participants compared to 89.1% (n = 49) in the placebo group. 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).
A fall was reported by more than 50% of the participants across all treatment groups. Amato and colleagues documented a slightly higher incidence of falls in the bimagrumab 3 mg/kg group compared with the bimagrumab 10 mg/kg, 1 mg/kg, and placebo groups (69.2% vs 56.6%, 58.8%, and 61.8%, respectively) without any clear dose-dependent trends or statistically significant differences observed.
From the core study baseline, differences in changes in sporadic inclusion body myositis functional assessment (sIFA) score increased progressively between the placebo and the 10-mg/kg bimagrumab groups up to week 78. At week 104, patients in the bimagrumab 10 mg/kg dose group started to experience a relative worsening, whereas the placebo group remained largely stable.
The incidence of serious AEs was comparable between the pooled bimagrumab (18.6%) and placebo groups (14.5%). Five deaths were reported during the study, none of which were considered to be related to the study medication.
"Findings from this study, which is the largest and longest ever conducted in sIBM, may help clarify disease progression and provide important input to consider when designing clinical trials testing the anticipated benefits of new investigational drugs,” Amato et al wrote.
In 2016, Novartis confirmed that the RESILIENT study examining bimagrumab did not meet its primary end point.2 There currently remains no approved treatment for sIBM and diagnosis of the disease is complex. To date, there is no single test that enables reliable diagnosis; because of this sIBM is often misdiagnosed.
More recently, a new study confirmed that treatment with bimagrumab is safe and effective for treating excess adiposity and metabolic disturbances in adult patients with obesity and type 2 diabetes. At the end of the 48-week study, researchers found a nearly 21% decrease in body fat in the bimagrumab group compared to 0.5% in the placebo group. The results also revealed the bimagrumab gained 3.6% of lean mass compared with a loss of 0.8% in the placebo group.3