Duchenne muscular dystrophy (DMD) is a severe, X-linked neuromuscular disease caused by mutations in the DMD gene, leading to the absence of dystrophin and progressive muscle weakness. Casimersen, a phosphorodiamidate morpholino oligomer, aims to bypass these mutations and produce a functional dystrophin protein in patients amenable to exon 45 skipping.
A multicenter, phase 1/2 trial enrolled 12 participants aged 7–21 years with limited or no ambulation. The study included a 12-week double-blind dose titration followed by an open-label extension for up to 132 weeks. Participants were randomized to receive weekly casimersen infusions at escalating doses or placebo.
Results showed that casimersen was well tolerated, with treatment-emergent adverse events (TEAEs) being mostly mild and unrelated to the treatment. No deaths, dose reductions, or serious adverse events related to casimersen were reported. Pharmacokinetic analysis indicated that casimersen plasma concentration increased with dose and declined similarly across all dose levels over 24 hours postinfusion, with no significant accumulation after long-term dosing.
The study concluded that casimersen has an acceptable safety profile and supports further studies in larger cohorts of DMD patients with mutations amenable to exon 45 skipping. The findings are significant for the development of targeted therapies for DMD, offering hope for improved management of this debilitating disease.
