Sarepta Therapeutics Inc. shares (NASDAQ:SRPT) fell 32.5 percent Monday to $15.91 as it revealed FDA requests for new data on its late-stage Duchenne muscular dystrophy (DMD) candidate, eteplirsen, would delay until mid-2015 a planned new drug application (NDA) for the therapy. The slowdown boosted shares of competitor Prosensa Holding NV (NASDAQ:RNA), which expects a rolling submission for its Duchenne's therapy, drisapersen, to be completed before year-end.

Sarepta president and CEO Chris Garabedian said although Sarepta knew that there were general concerns and skepticism around accepting dystrophin as a validated surrogate marker, the request for additional data was still surprising and disappointing, given the company's expectations. The Cambridge, Mass.-based company had been preparing for commercialization around summer 2015. Now, with the new information requested by the agency, he said, that effort will be pushed to early 2016 at earliest. (See BioWorld Today, April 22, 2014.)

The FDA said it's concerned about what it called "marked disparities" in methods used by Sarepta's investigators to measure levels of dystrophin, a protein key to improving the condition of boys fighting DMD. To address that, it's requiring an independent assessment of dystrophin-positive fibers from earlier studies as well as insisting Sarepta provide additional imaging, safety and patient-level natural history data as part of its NDA. The agency also wants to hold additional talks with the company to determine what would constitute a complete NDA before submission.

Sarepta outlined its NDA plans for the agency earlier this year, including its intention to supplement the application with additional data post-submission and during the review process. The approach was based on what Garabedian said in a Monday investor call was "the flexibility and openness conveyed by the FDA" in an April guidance letter as well as other interactions with the agency.

"By contrast now, this new guidance we just received described very specific data and additional data request that now need to be included in an NDA submission or at the same time as an NDA submission," Garabedian said.

The agency now wants Sarepta to provide an independent assessment of dystrophin images and 168-week clinical data from the phase IIb extension trial, study 202; three months of data from at least 12 to 24 new patients exposed to eteplirsen, including a minimum duration of safety; patient-level natural history data, to be obtained by Sarepta from independent academic institutions; and MRI data with appropriate natural history controls from a recent study conducted by an independent academic group. (See BioWorld Today, July 11, 2014.)

The FDA made its requests in meeting minutes provided to Sarepta last week following a September 2014 Type B pre-NDA meeting.

Joseph Schwartz, an analyst with Leerink Partners LLC, called the new requests "more arduous" than before, shaving his price target for Sarepta shares to $14 FDA from $24. In a note to clients, Schwartz wrote that the "FDA is concerned about the reproducibility of the eteplirsen histological data, which we've noted previously is gathered in what we believe to be a somewhat subjective manner when compared to RNA's automated methodology used for drisapersen."

DMD is an X-linked rare degenerative neuromuscular disorder causing severe progressive muscle loss and premature death. It affects about one in every 3,500 boys born worldwide. Eteplirsen is Sarepta's lead candidate, designed to address the underlying cause of DMD by enabling the production of a functional dystrophin protein.

The drug relies on phosphorodiamidate morpholino oligomer-based chemistry and Sarepta's exon-skipping technology to skip mutations affecting exon 51 of the dystrophin gene, which when mutated can produce non-functional dystrophin. Patients have demonstrated a broadly favorable safety and tolerability profile and restoration of dystrophin protein expression, the company said.

Shares of Prosensa, which now seems poised to beat Sarepta to market, closed at $12.56 Monday, up 55 cents. The company got a summer boost from the FDA in June when the agency provided it guidance for a potential regulatory path, under accelerated approval, for drisapersen. (See BioWorld Today, June 4, 2014.)

Shares of PTC Therapeutics Inc. (NASDAC:PTCT), which has a conditional marketing authorization for the nonsense mutation DMD therapy Translarna (ataluren) in the European Union, gained $1.18, to close at $37.63. (See BioWorld Today, Oct. 13, 2014.)

Sarepta has seen tough times before. Investors fled shares after the company released 144-week data from study 202 in July, data that the company characterized as favorable, but that heightened caution among others.

"If there's a silver lining that comes out of this delay," said Garabedian, " it's the understanding with great specificity of what the FDA needs to see to accept a filing for eteplirsen. So we'll continue to move forward with that goal in mind."