Sarepta plans FDA filing for Duchenne muscular dystrophy drug eteplirsen by year end, shares rise

Shares for Sarepta Therapeutics gained as much as 74 percent Monday after the company announced plans to apply to the FDA by the end of 2014 for authorisation to market its exon-skipping drug candidate eteplirsen to treat Duchenne muscular dystrophy (DMD). The plan to submit the new drug application under a potential accelerated approval pathway is based on a guidance letter from the agency that said "with additional data to support the efficacy and safety of eteplirsen for the treatment of DMD, [a marketing application] should be fileable," the company said.

CEO Chris Garabedian remarked that we "appreciate that the FDA shares our urgency in dosing a broader base of eteplirsen patients and has encouraged us to begin the clinical programme with our follow-on exon-skipping drugs as soon as possible." Previously, Sarepta had signaled that the FDA would review the phosphorodiamidate morpholino oligomer based on data from its mid-stage 201 study involving 12 boys with DMD who have appropriate deletions of the dystrophin gene. However, last November the regulator advised the company against seeking accelerated approval, citing negative results from a Phase III study of GlaxoSmithKline and Prosensa's similar drug drisapersen in DMD. At the time, the agency noted that a "disconnect between increased expression of dystrophin and clinical efficacy for drisapersen...raises considerable doubt about the biomarker."

Sarepta stated the agency outlined two potential pathways to accelerated approval. In one pathway, clinical data on 6-minute walk outcomes from the company's Phase IIb clinical trial programme, which includes Study 201 and the extension trial 202, "could be considered a finding on an intermediate clinical endpoint," while the other possibility involves "using a number of modalities to quantify dystrophin in muscle biopsies." The agency also proposed "a collaborative effort in which we will work to better understand the methods and analyses used for the existing biomarker data…[and] also work together on methods for the collection of additional data that could be more reliable."

Further, Sarepta said the FDA outlined two approaches for confirmatory studies for eteplirsen, including a historically-controlled trial and a placebo-controlled study of a related drug directed at a different exon mutation, that shows a correlation between dystrophin production and clinical benefit on 6-minute walk or another measure.

Based on the FDA's guidance, Sarepta said it plans to initiate several additional clinical studies this year with eteplirsen in exon-51 amenable genotypes, including one with predefined efficacy endpoints for ambulatory patients aged 7 to 16 years who can walk a minimum distance. The drugmaker will also complete two studies to evaluate safety and biomarker data with eteplirsen in patients with DMD who are younger than 7 years and in patients with DMD who cannot walk a minimum distance or have become non-ambulant. Further, Sarepta plans to initiate a placebo-controlled trial with one or more of its follow-on DMD exon-skipping drug candidates by the end of 2014. The company said it plans to begin dosing in the confirmatory eteplirsen study in the third quarter, with dosing in the additional trials initiated later this year.

Chief medical officer Edward Kaye commented that the FDA's guidance "allows us to move quickly into additional clinical trials with eteplirsen to confirm our current understanding of [the drug's] safety profile, its effect on dystrophin production, and its impact on clinical outcomes in DMD patients." Garabedian noted that "this provides the opportunity to get the drug approved and in the hands of all the boys who can benefit from it sometime in 2015."

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