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In stunning twist, FDA approves Sarepta’s Duchenne drug it rejected

The Food and Drug Administration on Thursday approved Sarepta’s Duchenne muscular dystrophy therapy Vyondys 53, four months after rejecting the drug over safety concerns.

The decision comes as a major surprise, as Sarepta had given no prior hints that it had resubmitted an application to the agency. Reversing a rejection so quickly is highly unusual.

After the FDA turned down its application, Sarepta appealed the agency’s decision through a formal dispute resolution process. Peter Stein, the director of the agency’s Office of New Drugs, resolved the issues raised in the Complete Response Letter issued to Sarepta, the company said, and granted the appeal.

Sarepta then filed its application again, resulting in the unexpected approval Thursday. It’s good news for Sarepta, which can now offer a second Duchenne therapy alongside its on-market drug Exondys 51. The regulator’s about-face also bodes well for Sarepta’s experimental casimersen, which works in a similar fashion.

Shares in Sarepta surged by 34% in Friday morning trading, boosting the company’s market value by about $2.5 billion.

A type of nucleic acid therapy, Vyondys 53 is now conditionally cleared for the roughly 8% of patients with Duchenne who are “amenable” to exon 53 skipping, the mechanism by which the drug works.

Sarepta said it would price Vyondys 53 “at parity” with Exondys 51, which controversially won FDA approval in 2016. Exondys 51 costs about $300,000 per year per child.

Exondys 51 was the first medicine specifically approved to treat Duchenne, covering about 13% of patients. Its approval sparked internal debate at the FDA, with agency officials at the Division of Neurology Products, the director of the Office of New Drugs and the acting chief scientist arguing in favor of rejection. They were overruled by Janet Woodcock, head of the FDA’s Center for Drug Evaluation and Research.

The FDA’s rejection of Vyondys 53 had stirred speculation the agency had done so for political reasons tied to the controversy over Exondys 51.

Company CEO Doug Ingram steadfastly refused to say much about the setback other than that it related to infection and kidney toxicity risks, and asked the patient community to not pressure the agency to change its mind.

Approval is conditional on Sarepta running a confirmatory study to prove Vyondys 53 delivers a clinical benefit. Per the FDA’s letter, testing must be completed by 2024.

The data Sarepta used to support its application showed that treatment increased levels of dystrophin, a critical muscle protein missing in patients with DMD, from 0.1% of normal to 1.02% on average after 48 weeks.

The OK also came with requirements to complete safety evaluations and to start post-marketing safety analyses specifically focused on kidney side effects. Renal toxicity was one issue Sarepta said the FDA had raised in its complete response letter.

Unlike Exondys 51, where ​Sarepta has yet to face competition, Vyondys 53 could soon see a rival approved. Japan’s NS Pharma said Oct. 2 it had completed an application to the FDA for its exon-skipping agent viltolarsen, which also targets exon 53.

Sarepta’s casimersen, designed for patients amenable to exon 45 skipping, could soon be submitted to regulators as well.  In its third quarter results filed with the SEC, the company said, “We plan to evaluate the submission of an [New Drug Application] for casimersen once we have further clarity on the CRL.”

“Some investors were leery that the CRL reflected a higher bar for DMD trials, but today’s reversal should placate those concerns,” wrote Joseph Schwartz, an analyst at SVB Leerink, in a Dec. 13 note to investors.

Further out is Wave Life Sciences, which is awaiting data from a study of its exon-skipping drug suvodirsen. If sufficiently positive, the company plans to seek an accelerated approval in the U.S.

Wave shares were up 7% Friday morning.