Patients with inclusion body myositis will have to continue to wait for an effective treatment since the latest randomised controlled trial of a potential therapy failed to impress.
The phase 2b RESILIENT study of bimagrumab versus placebo found no improvement in the primary outcome of six-minute walk distance (6MWD) or secondary outcomes including isometric muscle strength.
The international study – which involved investigators from Perth, Melbourne and Sydney – randomised 251 patients from 38 clinical sites to monthly infusions of bimagrumab at 1, 3 and 10mg/kg or placebo for 48 weeks.
It found there was no change from baseline in 6MWD with any dose of bimagrumab versus placebo at 52 weeks.
A dose-dependent increase in lean body mass was observed with bimagrumab at 3 mg/kg and 10 mg/kg compared to a loss of lean body mass with 1 mg/kg bimagrumab or placebo.
“However, our results are clear that the modest increase in lean body mass was not sufficient to lead to an improvement in muscle strength or physical function, as measured by 6MWD and quantitative muscle testing,” the study authors said.
The fall rate, swallowing efficacy, right hand-grip strength or right pinch-grip strength did not differ between patients in the treatment or control groups.
Muscle spasms and diarrhoea were the most frequently reported adverse events with the monoclonal antibody.
“No increase was noted in serious adverse events relative to placebo and no evidence of cardiac hypertrophy was seen in bimagrumab-treated participants, suggesting an overall favourable safety profile,” the researchers noted.
They added that Novartis, who funded the study, were not planning to pursue bimagrumab for this indication.
An accompanying editorial in The Lancet Neurology said bimagrumab could serve as an add-on component in future trials that aim to diminish muscle cell stress in patients with inclusion body myositis or other neuromuscular disorders.
“Modulation of the myostatin system in neuromuscular diseases will continue to be investigated, but will not be without hurdles. In that respect, bimagrumab seemed to be safe and well tolerated in the RESILIENT study.”
“For patients with inclusion body myositis, other drugs are awaited—eg, arimoclomol and sirolimus, two drugs that are available orally.”