Highlights from the Sarepta Webinar Regarding Etiplersen and Additional Exon Skipping Programs for Duichenne Muscular Dystrophy.

This is a very brief summary of some of the key points from this morning’s webinar hosted by Sarepta and moderated by Chris Garabedian, CEO and Ed Kaye, CMO.  CureDuchenne is proud to have been a supporter in the development of etiplersen and we appreciate this company update. The Duchenne community is keen to help expedite the progress of these programs.  The webinar in its entirety can be viewed at:  https://edge.media-server.com/m/p/sd8uchia/lan/en

Sarepta’s overall plan is to have as many as 20 drugs that would treat most of the out-of-frame deletions.  At this time they do not have drugs in development for duplication exons or mutations requiring a double skip.  They do, however, work closely with academic scientists who are looking into duplication mutations.  As a side note, although they did not specify which scientists they are working with, CureDuchenne has funded Dr. Kevin Flanigan at Nationwide Children’s Hospital over the last few years, for a new mouse model that carries a duplication of exon 2. (https://cureduchenne.org/blog/cure-duchenne-supports-duchenne-duplication-mutation-research-with-dr-kevin-flanigan/)

In the case of those mutations that require the skipping of two exons, Sarepta would first need to get class approval for their compounds and once the drugs were approved, it would be up to the physician, and possibly the FDA, to decide if this is a feasible strategy.  Since doses are already fairly high, doubling the amount of drug in a patient would have to be considered.

The etiplersen confirmatory study is being planned and first patients should be dosed in the first quarter of 2014.  This will be an open label study that includes 60 patients on drug and 60 patients that do not receive drug and have mutations amenable to skipping exons 44, 45, 50, and 53.  Biopsies will be randomized among the group, with 40 biopsy patients at baseline; 10 patients at 24 weeks, 20 patients at 48 weeks and 10 patients in the extension phase of the study.  The untreated group will qualify using the same criteria as the treated group, except for the different mutations.  The 6MWD will be the primary outcome measure with dystrophin a secondary measure.  Participants will be ambulatory and seven years or older, and will have been on stable corticosteroid use.

The pre-IND meeting for exon 45 is complete and they are conducting IND-enabling studies now.  For exon 53, the pre-IND meeting will be before the end of 2013 and the IND-enabling studies will commence before the end of this year.  They have identified the lead sequence for exon 50 and are in the process of identifying their lead sequence for exon 44.  Since all of these exons will be represented as the untreated group in the etiplersen confirmatory study, their plan is to have all of these patients roll over into a drug study group in the future.

Moving past these next 4 exons, they will need class approval since there won’t be enough patients to participate in a fully powered trial.

Sarepta is aware of the patients that were in the drisapersen trial that are no longer receiving that drug.  Sarepta is exploring the possibility to include the US and Canadian drisapersen placebo patients in their confirmatory trial.  There are no current plans to treat the drisapersen treated group, but they might possibly include an additional arm for these patients.

A few last points:  Sarepta does believe that the 6MWD is a good and sensitive endpoint. And they think that small amounts of skipping is happening in the heart, but they don’t know the clinical significance of it.  The two non-ambulatory boys showed evidence of stable pulmonary function.

Overall, this was a very positive report and Sarepta clearly has a well thought out plan.  All of us at CureDuchenne are very happy to see this progress and look forward to working with Sarepta in the future.

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