Letters of Support to the FDA for Exon Skipping

Posted by: Christine McSherry on November 19, 2012

Dear Community,

We are doing everything we can to help bring Eteplirsen to individuals affected by Duchenne as soon as possible.  One of the most powerful and useful actions any member of the Duchenne community can take is to share our stories.  Our voices make a difference. Our stories are effective and can help facilitate the delivery of potential treatments to market.  To utilize our voices in the most effective manner, we need you to start with YOUR story, the story that only you can share about your family, your child, yourself - to the FDA.

Instructions - Print the letter - sign with your name and address.  If possible, attach a photo, a brief write up and what exon your child needs skipped or how this treatment might help your child in the future.  Please mail it to Jenn McNary PO Box 295, Saxtons River VT 05154  or directly to Dr. Russell Katz at the FDA.

Russell G. Katz, MD
Division of Neuropharmacological Drug Products
Food and Drug Administration
10903 New Hampshire Ave
Silver Spring, MD 20993

Dear Dr. Katz:

I’m writing to ask your help expediting the FDA’s review of an investigational drug, eteplirsen, for the treatment of Duchenne muscular dystrophy.

In October, investigators led by Dr. Jerry Mendell of the Children’s Hospital of Columbus reported dramatic results in a 48-week long clinical trial of a new antisense RNA drug, eteplirsen, that treats one set of Duchenne patients ( with  mutations correctable by skipping exon 51).   Although this was a Phase IIb trial, and therefore enrolled only 12 patients, eteplirsen showed amazing results.  The children receiving the drug showed dystrophin, the protein missing in Duchenne patients, in their muscle cells and improved their ability to walk, whereas patients receiving placebos lost walking function.  These results were statistically significant and meaningful in terms of improved quality of life for these boys.  The study found no side effects.   The patients in the placebo group also showed improvements after they began receiving eteplirsen after 24 weeks.

What the numbers and graphs from this study don’t provide, however, is the profound human impact on the boys in the study.  The families of three of the eight patients who received eteplirsen from the beginning of the study have come forward to discuss the profound impact the drug has had on these boys.  They discuss how their children who had been confined to wheelchairs for most strenuous activities are now running, how boys who were unable to open milk bottles are able to do so, and on and on.

Sarepta Therapeutics, the company developing eteplirsen, will soon be meeting with the FDA to discuss your views on whether there is sufficient data right now for the FDA to review a new drug application for eteplirsen, and also to discuss the design of the next clinical trial.  I hope that, at that meeting, you and your staff will indicate that the FDA is willing to consider the accelerated approval of eteplirsen based on the data from the Phase IIb study (and the follow-on study, in which all 12 patients from the Phase IIb study are enrolled), subject to the requirement that Sarepta conduct a confirmatory trial.

The FDA, through its accelerated approval regulations and other actions, has been a leader in helping to bring life-saving treatments for otherwise untreated conditions to market quickly while maintaining protections for patient safety and high scientific standards.  Congress has shown that it agrees with the FDA’s steps, both in the FDA Modernization Act of 1997 and in this year’s Food and Drug Administration Safety and Innovation Act.  In particular, Section 901(a)(A) and (B) of the FDASIA state Congress’s intention to promote the development of “[a] new generation of modern, targeted medicines... intended to address unmet medical needs for serious or life-threatening diseases or conditions, including those for rare diseases or conditions,” which “may result in fewer, smaller, or shorter clinical trials for the intended patient population… without compromising or altering the high standards of the FDA for the approval of drugs.”

Eteplirsen meets all of the standards that Congress set out and that the FDA has applied in the past:  it is a modern, targeted medicine that addresses an unmet medical need for a serious and life-threatening rare disease.  While the clinical trial was small, its results, both in the replacement of the protein that is missing in Duchenne patients and in a quality of life measure, were both statistically significant and clinically meaningful.  The absence of any serious side effects gives us great comfort, laying a strong foundation for the FDA to consider accelerated approval of eteplirsen on the Phase IIb results.

The choice that the FDA faces is stark.  If you ask Sarepta to delay their NDA until after they have completed a Phase III trial, it means that hundreds of children will lose the chance, quite possibly forever, to achieve significant relief from the disability and early death that they currently face, and it will further delay the development of related compounds that might help those whose Duchenne is caused by mutations in other exons.   Given that we have a well controlled trial with remarkable results that raised no safety issues, and the FDA’s ability to withdraw eteplirsen if you approve the drug but find that the follow-up trial does not support the Phase IIb results, I believe that this is a chance that these children deserve.  Eteplirsen is exactly the kind of drug that deserves to be reviewed as soon as possible

As Janet Woodcock of the FDA said earlier this year, the FDA always needs to make a value judgment about the benefit to a patient for approving a drug to meet a serious and unmet medical need.  Given the strong performance and good safety profile of eteplirsen in the Phase IIb study, virtually every parent of a child with an eligible form of Duchenne would want eteplirsen available for his or her child.   Eteplirsen deserves to be reviewed on an accelerated basis using the Phase IIb data, and I hope you will support an expedited review.


Print Name


City,                                               State,                                               Zip Code

CC:         Gayatri R. Rao, MD, JD


Office of Orphan Products Development

Anne Pariser, MD

                Associate Director

Rare Disease Program

Robbin M. Nighswander, RPh
Chief, Project Management Staff
Division of Neurology Products

Jacqueline Ware, RPh
Supervisory Project Manager
Division of Neurology Products

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