On Monday morning, Sarepta Therapeutics (SRPT) held a teleconference concerning regulatory updates for Eteplirsen, the company's lead drug candidate for Duchenne Muscular Dystrophy.

In a Type B pre-NDA meeting Sarepta held with the FDA in September, the FDA provided updated guidance concerning Eteplirsen’s regulatory pathway and most importantly now, the data package to be included in the New Drug Application (NDA) for Duchene’s Muscular Dystrophy (DMD). Sarepta previously planned to file a New Drug Application by the end of 2014; however, due to additional data required in the NDA package, Sarepta is now guiding for a filing in mid-2015.

The FDA is requiring independent assessment of dystrophin images and 168-week clinical data from the on-going phase IIb extension Study 202 to be included in the NDA data package. In addition, the FDA wants minimum duration of safety in new patients exposed to Eteplirsen (3 months) and patient-level natural history data, to be obtained by Sarepta from independent academic institutions.

This latest guidance and regulatory requirements for Eteplirsen call into question management’s ability to constructively work with the FDA to advance Eteplirsen towards an approval. This is only the latest in a string of set-backs/modifications, and the update on Monday adds additional risk: the upcoming 168-week clinical data release, which includes 6-meter walk test (MWT) results, just turned into a binary event for Sarepta – the data generated from this time point must be “without a doubt” positive. Most importantly, the FDA has “uncovered marked disparities in the immunohistochemistry methodology and concerns about the reproducibility of the data. The lack of confirmation of robust dystrophin measurement […] necessitates including the independent assessment of dystrophin-positive fibers and 168-week efficacy data from study 201/202 in the NDA.” FDA is the latest and most concerning entity to join the chorus of investors calling the dystrophin data and the company's approach to measurements into question. The ability of Sarepta to provide valid and positive dystrophin data from subjects treated with Eteplirsen, up to the FDA standard’s, remains a key risk. It's also important to keep in mind that the FDA is still not set on what a “complete NDA” will include, and the data package is subject to change – yet another ongoing risk.

Despite these setbacks, Sarepta still plans to begin dosing the non-ambulatory and ambulatory phase III trials of Eteplirsen trial next month. Sarepta is also adhering to previous guidance that the company will collect 168-week clinical data and a 4^th biopsy from subjects in the ongoing phase IIb extension study.