Pilot study of canakinumab (Ilaris) in steroid naïve children with Duchenne muscular dystrophy demonstrates safety and exploratory changes in potential serum protein response biomarkers.

BACKGROUND: Duchenne muscular dystrophy (DMD) is a progressive muscular disease associated with muscle fiber degeneration and increased inflammatory responses including Interleukin-1 beta (IL-1β) and other cytokines. Canakinumab (Ilaris) is an anti-human IL-1β monoclonal antibody that neutralizes IL-1β.

METHODS: We completed an open-label, single dose pilot study of canakinumab 2 mg/kg subcutaneous injection in steroid naïve boys with DMD older than 2 years of age to determine safety and potential serum response biomarkers of efficacy at 4-weeks post treatment. Proteome profiling was performed using high throughput multiplexing aptamer SomaScan assay based technology targeting 1,500 unique serum proteins.

RESULTS: Three subjects completed the study with no adverse events reported and no significant changes in safety labs. Proteomic analysis within 4 weeks of treatment identified significantly decreased inflammation associated factors including plasma serine protease inhibitor, interleukin-6 receptor alpha, Lymphocyte antigen 86, Immunoglobulin D and myostatin. Significantly increased proteins included muscle-associated proteins aldolase A and lactate dehydrogenase B.

CONCLUSIONS: Canakinumab 2 mg/kg dose is safe for children with DMD and demonstrated potential response biomarkers of efficacy in treating related muscle disease. Canakinumab did not affect the circulating levels of IL-1β but did decrease some key proinflammatory markers and myostatin. Increased muscle specific proteins could be associated with increased physical activities or damage seen in young patients with DMD. Further studies using canakinumab for a longer treatment period may demonstrate increased benefit.