FDA clears Sarepta's Duchenne muscular dystrophy gene therapy

By The Science Advisory Board staff writers

February 26, 2021 -- The U.S. Food and Drug Administration (FDA) has cleared casimersen (Amondys 45), an antisense oligonucleotide, for the treatment of Duchenne muscular dystrophy (DMD) in patients with a confirmed mutation amenable to exon 45 skipping.

Exons are pieces of DNA that provide information for making proteins in a person's genome. Approximately 8% of patients with DMD have a mutation that is amenable to exon 45 skipping.

Casimersen was developed on Sarepta Therapeutics' phosphorodiamidate morpholino oligomer (PMO) chemistry and exon-skipping technology platform to bind to exon 45 of dystrophin pre-mRNA, resulting in exclusion, or "skipping," of this exon during mRNA processing in patients. Exon skipping is intended to allow for production of an internally truncated dystrophin protein.

The agency approved casimersen based on an increase in dystrophin (a protein that helps keep muscle cells intact) production in skeletal muscle observed in patients treated with the therapy. In the double-blind, placebo-controlled study in which 43 patients were randomized 2:1 to receive either intravenous casimersen or placebo, patients who received casimersen showed a significantly greater increase in dystrophin protein levels from baseline to week 48 of treatment, compared with those who received placebo.

Casimersen is approved under accelerated review based on an increase in dystrophin production in skeletal muscle of patients amenable to exon 45 skipping. Continued approval may be contingent on verification of a clinical benefit in confirmatory trials.

Sarepta is conducting the ESSENCE trial, an ongoing placebo-controlled confirmatory trial investigating casimersen. It is expected to conclude in 2024.

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