FDA clears Sarepta's exon-skipping therapy Amondys 45 for DMD

Sarepta Therapeutics on Thursday said the FDA granted accelerated approval to its filing for the antisense oligonucleotide Amondys 45 (casimersen) for the treatment of Duchenne muscular dystrophy (DMD) in patients with a confirmed mutation amenable to exon 45 skipping. CEO Doug Ingram remarked that "along with our other approved RNA therapies, we can now offer treatment options for nearly 30% of [DMD] patients in the US."

The decision makes Amondys 45 Sapreta's third RNA exon-skipping treatment for DMD approved in the country, after Exondys 51 (eteplirsen) and Vyondys 53 (golodirsen). Sarepta said its new therapy will be "priced at parity" with those two products, and commercial distribution will commence immediately. Amondys 45, also known as SRP-4045, uses the company's proprietary PMO platform to bind to exon 45 of dystrophin pre-mRNA, resulting in "skipping" of this exon during mRNA processing in appropriate patients.

The FDA filing included data from the Amondys 45 arm of the confirmatory Phase III ESSENCE trial involving 43 male patients between seven and 20 years of age with a confirmed mutation of the DMD gene that is amenable to exon 45 skipping. Participants were randomly assigned to receive either intravenous Amondys 45 or placebo.

Reasonable likelihood of benefit

An interim analysis found a significant increase from baseline in dystrophin production, as measured by Western blot, among Amondys 45-treated patients to week 48, compared with placebo. The FDA said the data submitted by Sarepta demonstrated an increase in dystrophin production that is "reasonably likely to predict clinical benefit" in DMD patients who are exon 45 amenable. The US regulator noted that this is the first FDA-approved targeted treatment for carriers of this type of mutation, who make up about 8% of the DMD population.

Regarding safety, Sarepta reported that the most common adverse reactions in the ESSENCE study that occurred more often with Amondys 45 than placebo were upper respiratory tract infections, cough, fever, headache, joint pain, and pain in the mouth and throat. The company also said that while no cases of kidney toxicity have been observed in clinical studies with Amondys 45, there have been some cases reported with other antisense oligonucleotides, including potentially fatal glomerulonephritis, so kidney function should be monitored in patients taking its product. The ongoing ESSENCE trial is expected to conclude in 2024.

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