FDA Approves Casimersen for Duchenne Muscular Dystrophy Amenable to Exon 45 Skipping

The Food and Drug Administration (FDA) granted approval for casimersen (Amondys 45; Sarepta Therapeutics, Silver Spring, MD) for treatment of Duchenne muscular dystrophy (DMD) caused by a dystrophin mutation amenable to exon 45 skipping. Casinmersen is an antisense oligonucleotide that blocks exon 45 of the dystrophin messenger RNA (mRNA) so that an internally dystrophin protein is produced. Approximately 8% of individuals with DMD have a mutation that is amenable to exon 45 skipping.

"Developing drugs designed for patients with specific mutations is a critical part of personalized medicine," said Eric Bastings, MD, deputy director of the Office of Neuroscience in the FDA's Center for Drug Evaluation and Research. "Today's approval of Amondys 45 provides a targeted treatment option for DMD patients with this confirmed mutation."

In the ESSENCE trial (NCT02500381), participants who received casimersen had a significantly greater increase in dystrophin protein levels over 48 weeks of treatment compared with placebo.  A clinical benefit of the treatment (eg, improved motor function) has not been established. In making the decision to approve casimersen, the FDA considered the potential risks associated with casimersen, the life-threatening and debilitating nature of the disease, and the lack of available therapy.

The ESSENCE trial is a double-blind, placebo-controlled study in which 43 participants have been randomly assigned 2:1 to receive either intravenous casimersen (30 mg/kg) or placebo. All participants were male, between the ages of 7 years and 20 years, and had a genetically confirmed mutation of the DMD gene that is amenable to exon 45 skipping. The most common adverse events observed in participants treated with casimersen were upper respiratory tract infections, cough, fever, headache, joint pain, and throat pain. Although kidney failure was not observed with casimersen, it has been seen with other antisense oligonucleotide treatments and thus should be monitored anyone treated with casimersen.