FDA approves Sarepta's exon 53-skipping therapy Vyondys 53

The FDA on Thursday granted accelerated approval to Sarepta Therapeutics' Vyondys 53 (golodirsen) for patients with Duchenne muscular dystrophy (DMD) who have a confirmed mutation of the dystrophin gene that is amenable to exon 53 skipping. Billy Dunn, acting director of the Office of Neuroscience in the FDA's Center for Drug Evaluation and Research, said Vyondys 53 becomes "the first treatment targeted specifically for this disease subtype," with the agency estimating that roughly 8% of DMD patients carry the mutation. Sarepta shares gained as much as 28% on the news. 

The agency had rejected Sarepta's filing seeking accelerated approval for Vyondys 53 in August, citing a risk of infections related to intravenous infusion ports, as well as renal toxicity seen in pre-clinical models of golodirsen and observed following administration of other antisense oligonucleotides (for further analysis, read ViewPoints: Surprise rejection has Sarepta getting déjà vu all over again). 

However, the FDA said Thursday that its accelerated approval was based on the surrogate endpoint of an increase in dystrophin production in skeletal muscle seen in some patients treated with Vyondys 53. According to the agency, data submitted by Sarepta showed a rise in dystrophin production that is "reasonably likely" to predict clinical benefit in patients who have a confirmed mutation of the dystrophin gene amenable to exon 53 skipping, although "clinical benefit of the drug, including improved motor function, has not been established." The FDA added that in making its decision it "considered the potential risks associated with the drug, the life-threatening and debilitating nature of the disease and the lack of available therapy." 

Sarepta CEO Doug Ingram said that with Vyondys 53, the company's second approved exon-skipping RNA therapy for DMD after Exondys 51 (eteplirsen), "we now offer treatment options for approximately 20% of those with DMD in the US." He explained that since receiving the complete response letter in August, the company filed a dispute resolution with the agency that ultimately culminated in a resubmission of its application. 

Sarepta indicated that the placebo-controlled, post-marketing ESSENCE trial to support the Vyondys 53 accelerated approval is expected to conclude by 2024. It added that commercial distribution of the drug will begin immediately, and Vyondys 53 will be priced "at parity" to Exondys 51, whose price has not increased since its launch in 2016. Exondys 51 has an average net price of $300,000 a year and generated sales of $301 million in 2018. 

Meanwhile, Nippon Shinyaku said in October that it completed a rolling FDA submission for viltolarsen, also known as NS-065, for the treatment of DMD amenable to exon 53 skipping. For related analysis, see ViewPoints: NS Pharma steps into the golodirsen void.



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