Another delay in the review of Sarepta Therapeutics Inc.'s proposed Duchenne muscular dystrophy treatment eteplirsen seems to have stoked more optimism that FDA eventually will decide to approve the product.

The company announced May 25, a day before the review goal, that the agency had said it would not have a decision in time.

FDA told the company it is continuing its "review and internal discussions" and "will continue to work past the PDUFA goal date," but strive to complete the review "in as timely a manner as possible," Sarepta said in a statement.

A company spokesman told the Pink Sheet that FDA did not provide any additional details on the timing of a decision.

Sarepta is seeking accelerated approval of eteplirsen for treatment of Duchenne in patients that have a gene mutation amendable to exon 51 skipping.

The lack of a set extension of the goal date suggests FDA has not received additional data or other information that would have constituted a major amendment to the application and triggered a three-month extension of the review goal.

RBC Capital Markets analysts said in a note that they expect a decision in four to six weeks. But even though the extra time will allow supporters more time to lobby FDA for approval, RBC still expects a "complete response" letter.

The Case For Optimism

Optimists argue the delay is a sign that an approval is imminent and that FDA needs extra time to wrap up pending issues. Often FDA will decide to miss a goal date in order to finish a review, particularly if it is moving toward approval, and avoid forcing another review cycle.

One reason the agency might need more time is that the advisory committee meeting for eteplirsen also was only a month ago. While considered a significant milestone and potential predictor of approval, there still is a significant amount of work left for FDA reviewers once it is completed.

But focusing on the impact of the advisory committee probably doesn't support prospects for approval, however, since the panel meeting was overwhelmingly negative for the product.

Another possible reason for the delay is that FDA officials really are undecided about whether to approve the product, which has scant evidence of efficacy but would become the only treatment for Duchenne. If there is conflict within agency about whether to approve eteplirsen, a delay to broker some sort of solution would make sense.

The Case For Pessimism

Analysts at Leerink Partners also asked in a note whether the delay "is designed to ensure that it appears that the agency is adequately factoring in every possible stakeholder's input before rejecting the application."

If FDA does not plan to approve eteplirsen, it has no incentive to delay the decision. Sarepta most likely would prefer to know as soon as possible in order to begin making the necessary changes, should it intend to resubmit the application.

Indeed, goal date misses are not always a positive sign. The agency missed the review goal for eteplirsen's potential competition in Duchenne, BioMarin Pharmaceutical Inc.'s drisapersen, proposed trade name Kyndrisa.

More than two weeks after the goal date, BioMarin announced that it had received a "complete response" letter. There were a number of questions about the product's efficacy and potentially serious safety problems Also see "BioMarin's Drisapersen 'Compete Response' Shows FDA Flexibility Still Limited" - Pink Sheet, 14 January, 2016..

Eteplirsen also suffered from efficacy questions ([A#14160421004]) and the Peripheral and Central Nervous System Drugs Advisory Committee voted against recommending approval ([A#14160425005]).

This is the second formal delay of the eteplirsen review. The product had an advisory committee meeting scheduled in January, but an approaching snow storm forced its postponement ([A#14160120005]).

The storm, along with Sarepta's submission of additional data, led to a review goal extension ([A#14160310003]).

Access May Be Retained No Matter The Outcome

Patients receiving eteplirsen through its clinical studies still have access, Sarepta said.

And it is possible that like drisapersen, those patients on eteplirsen would retain access even if FDA issues a "complete response" letter.

Sarepta has not suggested that it would walk away from eteplirsen's development should it receive a "complete response" letter. It also already is enrolling one of the trials it plans to use as a confirmatory study should it receive an accelerated approval.

A second study is expected to begin enrolling soon.

Among the concerns about an accelerated approval for eteplirsen is whether a placebo-controlled confirmatory trial would be required. Such a study may not be possible once the drug is approved ([A#00160502007]).

Pressure On FDA Mounts

Eteplirsen has garnered an extraordinary amount of attention from patients, advocates and even Capitol Hill as it has wound its way through the review process.

Debra Miller, CEO and founder of CureDuchenne, a patient group that provided early funding for eteplirsen's development, said in an interview that she could accept the delay if it meant the agency was taking the necessary steps to approve the product.

Miller said she wants FDA to take the time to get it right.

"Every day that's not a 'No' is a good day," she said. "I'm looking at his hopefully."

But Miller also said in a statement that there is no unlimited horizon for patients, who continue to wait for approval of any treatment that can help slow the debilitating and ultimately fatal disease.

"We cannot afford to lose another generation of boys to Duchenne because there weren't treatment options," she said in the statement. "It is urgent to get the right combination of approved treatments for our boys."

Parent Project Muscular Dystrophy, another patient group, also maintained its prospects for eteplirsen's approval.

"We remain hopeful that the FDA is using this time to ensure that the collective voice of the community is being taken into account in this decision," the group said in a blog post.

Patient involvement in the drug development process reached a new milestone when a group spoke about data it had gathered during Sarepta's advisory committee presentation on eteplirsen ([A#00160502008]).

Interestingly, it was optimism about the drug's effect in slowing Duchenne's progression that may have hurt it during the review. Early positive results boosted calls for approval by the patient community, but the limited additional clinical studies the firm conducted did not yield data that was as robust as the initial findings.

Patient groups continued to argue that the product was efficacious, including during the advisory committee meeting. Dozens of patients, parents and advocates testified for several hours about the improvements they have seen ([A#14160425005]).

Patients also enlisted members of Congress to pressure FDA for approval. Most recently, Republican Sens. Ron Johnson of Wisconsin and Dan Coats of Indiana sent a letter to FDA Commissioner Robert Califf asking the agency to use its approval flexibility when considering eteplirsen.

The agency has a long track record of flexibility when it comes to clearing drugs for rare diseases Also see "FDA Orphan Approval Flexibility Remains Steady As Pressure Increases" - Pink Sheet, 27 October, 2014., but basing an approval on a dataset as small as Sarepta's would appear unprecedented.

Advocates also used a congressional hearing on expanded access policy to push for eteplirsen's approval Also see "Sarepta's Eteplirsen Is Centerpiece Of Senate Hearing On Expanded Access" - Pink Sheet, 26 February, 2016..

Sarepta's Eteplirsen Review Delay Emboldens Duchenne Community

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