Phase 3 interim results show casimersen safe, efficacious in Duchenne muscular dystrophy

Key takeaways:

• Children treated with casimersen had statistically significant increases in exon 45 skipping at 48 weeks compared with baseline.

• Casimersen was well-tolerated with mild adverse events, none related to treatment.

Treatment with casimersen increased exon 45 skipping from baseline and was well-tolerated in children with Duchenne muscular dystrophy, according to a poster at the 2023 MDA Clinical & Scientific Conference.

“Casimersen is FDA-approved for the treatment of Duchenne muscular dystrophy (DMD) in patients with a confirmed DMD gene mutation amenable to exon 45 skipping,” Susan Iannaccone, MD, professor and Warren A. Weinberg Endowed Chair for Pediatric Neurology and Learning at the University of Texas Southwestern Medical Center, and colleagues wrote.

Researchers sought to evaluate the safety and efficacy of casimersen and golodirsen in children aged 7 to 13 years with DMD who were on a stable dose of corticosteroids. They conducted the double-blind, placebo-controlled, phase 3 ESSENCE trial, which evaluated the two drugs over 96 weeks, followed by a 48-week open-label period.

A total of 229 children were enrolled and randomized on a 2:1 basis to receive 30 mg/kg of IV casimersen, 30 mg/kg of golodirsen or placebo once per week. Clinical efficacy was assessed during regularly scheduled study visits, and muscle biopsies were performed at baseline and week 48 or week 96.

According to 48-week interim biopsy results on the first 43 patients amenable to exon 45 skipping, participants in the casimersen group (n = 27) demonstrated statistically significant increases in exon 45 skipping, which was assessed by droplet digital PCR, compared with baseline. Researchers also reported increased mean dystrophin levels via Western blot analysis after 48 weeks of casimersen compared with placebo (mean difference = 0.59%).

Further, immunofluorescence indicated that patients treated with casimersen had a statistically significant increased mean percent dystrophin-positive fibers from baseline to week 48 (6.46% vs. 15.26%) and compared with placebo (mean difference = 8.29%). The mean fluorescence intensity increase was also statistically significant in patients given casimersen compared with placebo at week 48.

Researchers additionally reported that casimersen was well-tolerated, with most adverse events mild and unrelated to the drug itself. There was no indication of renal toxicity.

“Casimersen-treated patients had significantly increased exon skipping from baseline and dystrophin production with correct localization to the sarcolemma,” Iannaccone and colleagues wrote. “The safety and efficacy of casimersen will continue to be evaluated.”