FDA Asked to Approve Casimersen, Exon 45 Skipping DMD Therapy

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by Forest Ray PhD |

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Sarepta Therapeutics has submitted a full application to the U.S. Food and Drug Administration (FDA) seeking approval of casimersen (SRP-4045) to treat Duchenne muscular dystrophy (DMD) patients amenable to exon 45 skipping.

“The completion of our casimersen submission is an important milestone in our journey to advance treatments for the greatest possible number of people living with Duchenne muscular dystrophy,” said Doug Ingram, Sarepta’s president and CEO, in a press release.

Duchenne, the most common type of muscular dystrophy, is caused by mutations in the DMD gene, which provides instructions for a protein called dystrophin. This largest human gene has 79 exons — the actual protein-coding sequences — that need to be stitched together after the conversion to RNA to produce dystrophin.

Exon-skipping therapies are intended to exclude, or skip, a specific exon in the production of dystrophin, resulting in shorter but functional protein. Casimersen is specifically designed to skip over exon 45, an approach that could benefit nearly 8% of DMD patients, according to Sarepta.

Casimersen’s rolling new drug application (NDA) includes data from the Sarepta-sponsored Phase 3 ESSENCE trial (NCT02500381). The global, double-blind study is evaluating the safety and efficacy of casimersen and Vyondys 53 (golodirsen) in patients with mutations amenable to exon 45 skipping in the case of casimersen, and to exon 53 skipping with Vyondys 53.

ESSENCE aims to enroll 222 children, ages 7 to 13, and is still recruiting at locations in Australia, Canada, Europe, and the U.K. More information on contacts and study sites can be found here.

Preliminary data showed that patients treated with casimersen — via once-weekly intravenous (into-the-vein) infusions at a dose of 30 mg/kg — had significantly higher dystrophin levels than at baseline (the start of the study) and as compared to patients given a placebo. This analysis was based on data from muscle biopsies taken at baseline and again after 48 weeks of treatment. Total treatment time in ESSENCE is 96 weeks.

Should the FDA approve casimersen, the remainder of the ESSENCE trial will serve as a post-marketing confirmatory study, Sarepta stated. Such studies contribute additional information about a product’s safety, efficacy, and optimal use.

Casimersen could become the company’s third approved therapy for DMD. Besides Vyondys 53, Sarepta also markets Exondys 51 (eteplirsen) for patients amenable to exon 51 skipping.

“Together with our other approved therapies, we have the potential to treat nearly 30% of Duchenne patients in the United States,” Ingram said in the release.