Eteplirsen regulatory update

Sarepta said it plans to submit an NDA to FDA seeking accelerated approval of eteplirsen to treat Duchenne muscular dystrophy (DMD) by year end, with potential approval in 2H15, after the agency provided updated guidance. Sarepta had been planning to submit an NDA this half, but in November said approval of eteplirsen could be delayed by at least 2 years after FDA said it had "considerable doubt" about 6-minute walk test (6MWT) data from eteplirsen's Phase IIb program as well as the use of dystrophin as a surrogate endpoint (see BioCentury, Nov. 18, 2013). Eteplirsen - a phosphorodiamidate morpholino oligomer (PMO) targeting exon 51 - has Orphan Drug designation in the U.S. and EU and Fast Track designation in the U.S. for DMD.

The company said FDA outlined 2 potential pathways to accelerated approval. One way involves using 6MWT data from eteplirsen's Phase IIb program, though the agency expressed "significant concerns" with the existing dataset. Sarepta said it will collect additional 6MWT data from patients in the ongoing open-label Study 4658-US-202 extension of the double-blind, U.S. Phase IIb Study 4658-US-201 trial to supplement existing 6MWT data and/or pulmonary function test data. The second pathway involves using "a number of modalities to quantify dystrophin" in muscle biopsies and how the "biomarkers might be used as a surrogate endpoint(s) to support accelerated approval." Sarepta said FDA will be meeting with pathologists supervising the dystrophin quantification in the trial over the coming months to better understand the methods and "conditions in which the various dystrophin measures were conducted." According to Sarepta, FDA also advised taking a fourth muscle biopsy in patients who are continuing in Study 202 to support the dystrophin endpoint. The company said it will explore the possibility and may pursue biopsies later this year. Additionally, FDA said that the company should expect an advisory committee meeting to discuss the NDA, if the application is accepted. ...