Duchenne Muscular Dystrophy Statement

FDA recognizes the unmet medical need in Duchenne muscular dystrophy (DMD), the devastating nature of the disease for patients and their families, and the urgency to make new treatments available.  We remain committed to working with all companies to expedite the development and approval of safe and effective drugs to treat this disease.
On October 27, 2014, Sarepta Therapeutics released a statement and had a conference call regarding guidance received from FDA in a September 2014 meeting regarding its planned New Drug Application (NDA) for eteplirsen, to treat patients with DMD.  To the extent allowed by laws restricting release of confidential information about experimental drugs, FDA is addressing questions the agency has received from DMD patients, their families, and others in the community who are concerned about the timing of the filing of an NDA for eteplirsen.

Over the past several years, FDA has worked extensively with Sarepta on the development of eteplirsen, and provided guidance with respect to the data that would be necessary to determine whether it is effective and support filing of an NDA.  Following a meeting with FDA last April, Sarepta announced on April 21, 2014, that "with additional data to support the efficacy and safety of eteplirsen for the treatment of DMD, an NDA should be fileable."  Sarepta also announced at that time that FDA had communicated that there were areas of concern in the existing database, and that FDA had provided Sarepta with "examples of additional data and analyses that, if positive, would be important to enhance the acceptability of an NDA filing…."  Sarepta announced at the time its plans to submit an NDA for eteplirsen by the end of 2014.

Since the April 2014 meeting, FDA has been working intensively to help Sarepta provide the additional data and analyses needed to support an NDA.  FDA understands the considerable disappointment in the Duchenne community following Sarepta's October 27 announcement that the previous time frame for submitting the NDA for eteplirsen cannot be met.

In its advice to Sarepta, FDA has consistently stated that it would be necessary to include data in its NDA demonstrating that eteplirsen increases production of the muscle protein dystrophin.  (Eteplirsen's proposed mechanism of action is through increasing production of this muscle protein.)  As described by Sarepta in its October 27 statement, the need for additional data and analyses to support the NDA was reinforced by an FDA inspection of the clinical site where dystrophin analyses had been conducted.  It is important to note that the agency did not find any evidence of fraud at this site, as has been perceived by some.  FDA is concerned that the methods used to measure dystrophin were not adequately robust to support an NDA submission.  Thus, FDA provided Sarepta with detailed recommendations on how to improve these dystrophin analyses, and FDA's most recent advice was consistent with the advice provided after the April 2014 meeting. 

FDA has also been consistent in its guidance to Sarepta that it would be necessary to submit data from the ongoing open-label trial of eteplirsen (Study 202) in an NDA, along with data from natural history studies that could show that patients treated with eteplirsen experienced slower decline in physical function.  FDA has worked closely with Sarepta in efforts to obtain these natural history data from investigators.

FDA has consistently advised Sarepta that data from additional patients, beyond the patients included in Study 202, would be critical to our assessment of the safety and efficacy of eteplirsen.  In our April 2014 letter to Sarepta, FDA strongly encouraged Sarepta to begin enrollment of new patients as soon as possible.

FDA has expressed willingness to conduct a "rolling review" of Sarepta's NDA.  Under a rolling review, companies can submit, and FDA can review, portions of an application as they are completed.  Once submission of all components is complete, the review clock begins.  FDA expects the NDA for eteplirsen will qualify for a priority review.

FDA also plans to present the NDA for eteplirsen to a public advisory committee meeting before making a decision on approval.  This will afford FDA the ability to gain advice from outside experts and interested stakeholders on the adequacy of the data to support approval, including the possibility of "accelerated approval" – a mechanism to approve drugs in particular situations prior to the availability of definitive evidence of effectiveness.

FDA understands the dire urgency of the situation and the importance of our actions to the DMD community.  FDA will continue to work with Sarepta in their efforts to provide the data  it considers critical to FDA's ability to review the NDA and reach a decision on approvability.

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