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Sarepta, after two dramatic approvals, gets an FDA review for next Duchenne drug

Dive Brief:

  • Sarepta Therapeutics said Tuesday that the Food and Drug Administration has begun a review of its third agent for Duchenne muscular dystrophy (DMD), which puts it on track for a possible approval by Feb. 25. The experimental drug casimersen treats a different set of patients than its first two drugs, Exondys 51 and Vyondys 53.
  • As with the two approved drugs, Sarepta is seeking approval for casimersen primarily on data showing that the experimental candidate boosted levels of a key muscle-building protein. The company has faced criticism from the FDA for not completing a trial confirming that those protein increases stimulated by Exondys help change the trajectory of the disease. 
  • Approval of both Exondys and Vyondys were marked by controversy. Senior FDA officials overruled staff scientists and a panel of outside advisers to approve Exondys, while the agency initially rejected Vyondys before reversing itself, in spite of safety concerns raised by reviewers.

Dive Insight:

Casimersen, now expected to be called Amondys 45, is the third Sarepta drug of its kind that blocks a genetic mutation preventing the body from producing the muscle-building protein dystrophin.

The specific mutation casimersen treats involves a missing portion of the dystrophin gene called exon 45, while Exondys and Vyondys treat patients who are missing exon 51 or 53 respectively. About 8% of DMD patients have a mutation affecting exon 45. A similar number have a mutation that makes them eligible for Vyondys, while some 13% of DMD patients can be treated with Exondys.  

The treatment strategy, called “exon skipping,” allows a shortened version of dystrophin to be produced. However, the amount produced is small, less than 2%of the amount of dystrophin produced by people without DMD, according to interim results from the trial Sarepta submitted for FDA review.

Nonetheless, the FDA, as a whole, has viewed similarly modest benefits for Exondys and Vyondys positively, given a lack of other treatment options and the likelihood of a positive effect on the disease.

That view is not universally shared within the halls of the FDA headquarters, however. Exondys looked headed for a rejection in 2016 after a 7-6 vote against recommending approval and staff views that dystrophin production needed to be in the range of 10% of normal to produce a meaningful benefit. Top FDA drug evaluator Janet Woodcock overruled fellow agency reviewers, however.

That debate spilled over into review of Vyondys, which was initially rejected because of the risk of infections and worrisome signs seen in animal tests. 

In announcing the start of a review for casimersen, Sarepta said the FDA has indicated it will not convene an expert panel to consider the drug ahead of its approval decision. With the precedent of Exondys and Vyondys approvals on modest dystrophin increases — and, more recently, the agency’s clearance of a similar, rival drug from NS Pharma — casimersen’s approval looks likely unless the review reveals more safety concerns.

Sarepta’s gene therapy SRP-9001, meanwhile, overshadows development of its exon-skipping pipeline. That experimental treatment has shown encouraging signs of increasing dystrophin production and improving patient mobility in early-stage testing, and could apply to a broad swathe of patients instead of treating individual mutations on a piecemeal basis. 

Originally posted on