Sarepta Therapeutics has completed the submission of the casimersen (SRP-4045) New Drug Application (NDA) for the treatment of Duchenne muscular dystrophy (DMD) in patients who have genetic mutations that are amenable to skipping exon 45 of the Duchenne gene.

Casimersen is a phosphorodiamidate morpholino oligomer that works by binding to exon 45 of dystrophin pre-mRNA, resulting in exclusion of this exon during mRNA processing. Exon skipping allows for the production of an internally truncated but functional dystrophin protein.

The NDA is supported by data from the multicenter, double-blind, placebo-controlled phase 3 ESSENCE study, which assessed the efficacy and safety of casimersen and golodirsen in DMD patients amenable to skipping exons 45 or 53, respectively. Exon 45 amenable patients were randomized to receive casimersen via intravenous (IV) infusion once weekly (n=27) or placebo (n=16) for 96 weeks.

Interim analysis showed that treatment with casimersen resulted in a statistically significant increase in mean dystrophin protein to 1.736% from a mean baseline of 0.925% of normal (P <.001). A statistically significant difference was observed between the groups in the mean change from baseline to week 48 in dystrophin protein (P =.009). 

Moreover, all 22 patients receiving casimersen who had been tested for increased exon-skipping mRNA had an increase in skipping exon 45 compared with baseline levels (P <.001). Findings also showed a positive correlation between exon 45 skipping and dystrophin production (Spearman rank correlation = 0.635; P <.001).

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“If approved, casimersen will be our third approved therapy for subpopulations of Duchenne,”  said Doug Ingram, President and CEO, Sarepta Therapeutics. “Together with our other approved therapies, we have the potential to treat nearly 30% of Duchenne patients in the United States.”

The completed ESSENCE study will serve as a postmarketing confirmatory study if the NDA for casimersen is granted accelerated approval. 

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