Promising News from Sarepta on Exon 51 Skipping Trial

The much-anticipated 48-week results on eteplirsen, a drug designed to skip exon 51, were presented today by Sarepta Therapeutics on a webinar and press release. On the webinar, Sarepta’s Chief Executive Chris Garabedian presented data about the dystrophin found in study participants’ muscle biopsies and the 6-minute walk results.


To read some background about this clinical trial, click here.


An overview of the data reported today:

  • Chris presented results from the phase IIb study, which continued into an open-label extension study. The data that they presented included:
    • the change in dystrophin positive fibers, which was the primary endpoint for the clinical trial, and
    • the change in the 6-minute walk test, which was the primary clinical endpoint for the open-label extension part of the clinical trial.

  • There are 12 people with Duchenne in this clinical trial. For the first 24 weeks, they were randomly chosen to get 50mg/kg of eteplirsen, 30mg/kg of eteplirsen, or to be on placebo. They are now all in the open-label extension study, and all 12 are now getting either 50 or 30mg/kg of the drug.

  • The 48-week data shows that:
    • The children treated with eteplirsen have significantly more dystrophin-positive fibers in their muscles (with an average 47% increase for those who have been on drug for 48 weeks), and the number of dystrophin-positive fibers has increased over time as the children are on the drug longer. Children who started out on placebo and who are now on the active drug also show improvement in the number of dystrophin-positive fibers.

    • Children on the drug also improved in the 6-minute walk test. Children on drug had an average 21 meter improvement in their walk test, while children on placebo had a decline of 68 meters.

    • The data don’t yet tell us clearly whether 50mg/kg is better than 30mg/kg.

    • Children who were younger when the trial started, as well as those who had better walk test scores when the trial started, seemed to have more benefit from the drug. The two children who lost the ability to walk during the trial also had more dystrophin-positive fibers over time. However, this is a very small study and not all of the data has been analyzed, so it is too early to say who is most likely to benefit and how.

    • There were not any treatment-related adverse events during the study, which adds important information about the safety of the drug.

What's next?

  • Sarepta is still working on the analysis of this data and will present more information at the World Muscle Society meeting. They will also be presenting their information to the PPMD community on October 23rd at 1:00 pm Eastern- come learn more and ask your questions!

  • In the meantime, Sarepta is getting prepared to talk to the FDA about the results and discuss next steps. They are hoping to make a case for accelerated approval of Eteplersen. (PPMD continues to be in constant communication with our partners in Washington about the role of patient advocacy in this process. We will alert the community about actions that should be taken. Make sure you're signed up for our action alerts!) They are also starting to plan for a phase III/confirmatory trial. They understand that the community is likely to be negative about a trial that includes a placebo group after such promising results from this phase II study, and are trying to come up with trial designs that do not include a placebo group and that are acceptable to the FDA. They are also working on another important issue, which is scaling up their production so they can make enough of the drug to give to people in the confirmatory clinical trial (and hopefully, later to any person with Duchenne who would benefit from skipping exon 51).

For more details about the findings, read Sarepta's news release.

Also read Beyond Exon 51, a blog from PPMD's Senior Research Director, Sharon Hesterlee, explaining how an exon 51 success can benefit all people with Duchenne, regardless of mutation.

We are hopeful and very enthusiastic about these promising findings. We will keep you updated on what we learn at the World Muscle Society meeting, and please tune in for PPMD’s webinar with Sarepta on October 23rd at 1:00 pm EST.

Learn more: 

Holly Peay, Vice President, Education & Outreach
Read more PPMD Staff Blogs

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Comment by Keith Van Houten on October 5, 2012 at 1:44pm

Has Sarepta published anything more specific than the mean delta values?  Would data from individuals in the study typically be shown at something like the muscle conference?

Comment by Holly Peay on October 4, 2012 at 3:35pm

Hello Keith, thank you for that clarification.  You are right, it is 47% of normal; I apologize for the typo.  I can't speak specifically to the downstream issues with the FDA and the phase III study, except to say that on the Oct 3 webinar, Serepta's CEO described very cautious optimism and an intent to discuss accelerated approval with the FDA.  We are eager to know how the newly passed version of PDUFA (Prescription Drug User Fee Act) legislation with its modernization of accelerated approval provision will affect those decisions. Of course it will be in the FDA's hands and I don't think anyone knows whether the odds are good or bad.  Personally, I’m interested in hearing from Serepta about the more detailed analysis from this study, which will be presented at the World Muscle Society meeting next week.  We’ll keep the community updated as more information comes in.

Comment by Keith Van Houten on October 3, 2012 at 9:58pm

Point of clarification:  The Sarepta release says it was an increase to 47% of normal, not a 47% increase.


Can you talk a little about what the accelerated approval process Sarepta is applying for means, in terms of what additional clinical trials would or would not be required, what the endpoints might be, how fast the drug could concievably be available to people, and how insurance coverage is impacted?


Also, any information available on how large a phase III / confirmatory trial Sarepta is planning for?




the prospects for accelerated approval?  Could an accelerated approval be granted solely on the basis of the Phase IIb results, with a post approval confirmatory trial?  If they're granted accelerated approval, does the drug go only to those in the confirmatory trial, or anyone that wants it?   

Comment by PPMD on October 3, 2012 at 7:11pm

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Comment by jenn on October 3, 2012 at 7:06pm

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