Rare Disease Report

FDA Tells Sarepta - More Data, Please. NDA Submission for Eteplirsen Delayed.

OCTOBER 27, 2014
James Radke

This morning, Sarepta Therapeutics held a conference call explaining the latest requests from the U.S. Food and Drug Administration (FDA) regarding the requirements needed for New Drug Application (NDA) submission for the approval of eteplirsen to treat patients with Duchenne muscular dystrophy (DMD).  The additional requests mean that Sarepta will likely not submit the NDA until mid-year 2015. The additional requests also led to a 36% price drop in premarket trading.

Based on minutes from a Type B Pre-NDA meeting held in September, the FDA has informed Sarepta that the following additional information should be included in their NDA submission for eteplirsen:
  • "The sponsor should include 3-month data from at least 12 to 24 newly exposed patients at the time the NDA is submitted."

  • "Available data from the other patients enrolled in the new eteplirsen studies (studies 301, 203, 204) should also be included at the time the NDA is submitted, even if exposure is less than 3 months in duration."

  • "Additional data from later time points and from newly enrolled patients should be submitted in the 120-Day Safety Update."

  • "FDA strongly advises the sponsor to obtain and submit patient-level natural history data. FDA is prepared to appeal to the academic groups holding the data to allow the sponsor a means to acquire the data."

  • "The study 201/202 clinical site inspection conducted in May, 2014, after the issuance of the April 15, 2014, guidance letter, uncovered marked disparities in the immunohistochemistry methodology and concerns about the reproducibility of the data. The lack of confirmation of robust dystrophin measurement during the site visit necessitates including the independent assessment of dystrophin-positive fibers and 168-week efficacy data from study 201/202 in the NDA."

  • “FDA strongly urged the sponsor to submit the MRI data with appropriate natural history controls.”

  • “additional discussion between the sponsor and the FDA will be necessary to determine what would constitute a complete NDA.”

In a press release, Chris Garabedian, president and chief executive officer of Sarepta Therapeutics said:

"We are committed to satisfying the FDA’s updated requests for these specific data to be included as part of an NDA submission and will continue to work with the Agency toward the goal of a complete and acceptable NDA filing."

"We believe all of the data requests and additional FDA discussions that have currently been outlined can be completed in time for an NDA submission by mid-year 2015. Obtaining an FDA approval of eteplirsen for the DMD patients who may benefit from the drug continues to be our highest priority.”

During a conference call, Mr Garabedian said that while they are disappointed with the additional requests, they are committed to getting eteplirsen approved for the Duchenne community and will comply as best they can. Moving forward, the company will be meeting with the FDA later this year to address any questions they have about the additional requests. The company is also moving forward with the pivotal trials needed to get approval. 

Assuming all goes as plans, Sarepta hopes to submit their NDA mid-year 2015 and if eleplirsen is given accelerated approval, they hope to get the drug approved as early as 2016. 

About Duchenne Muscular Dystrophy

Duchenne muscular dystrophy is a progressive muscle disorder caused by the lack of functional dystrophin protein. Patients with Duchenne muscular dystrophy lose the ability to walk as early as age 10 and experience life-threatening lung and heart complications in their late teens and twenties.

There are an estimated 35,000 patients with Duchenne in the United States and Europe but the population has many subsets based on mutations of the dystrophin gene.

There are currently no treatments for these patients but several drugs are in late stage clinical development, including Both Sarepta’s eteplirsen and Prosensa’s drisaperson which should be effective in the same 13% of the Duchenne population who would benefit from exon 51 skipping therapy (i.e., those with mutations near exon 51 of the dystrophin gene) and PTC Therapeutics’ ataluren which  should be effective in another 13% subset who have nonsense mutations in the dystrophin gene. Lilly’s tadalafil is also in a phase 3 clinical trial.

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