No progress in 15 months, except for further decline…

Posted by: Christine McSherry on January 21, 2014


Right now we have the chance to collaborate with the FDA, benefit our community as well as the entire rare disease community for years to come. We cannot let this opportunity slip by.

The year 2013 slipped by. Before we knew it, and the reality that we have begun a “New Year”, 2014, is still trying to sink in. The quest started October 2012, 15 months ago, when we saw the compelling dystrophin data presented by Sarepta Therapeutics – the 48 week biopsy data that showed the missing protein in Duchenne being made by the compound eteplirsen. All 12 of the trial participants were making robust amounts of the dystrophin protein, and 10 were demonstrating statistically significant clinical evidence in the 6MWT. As we enter into 2014, allparents, advocates and supporters of Duchenne must ask ourselves thefollowing difficult question; how did this time slip by without any progress? How can we not be any further in the approval process of such a miraculous drug?

This weekend, I read the story of a therapeutic in Multiple Sclerosis, Lemtrada – made by Sanofi. A drug that has been recently approved in 30 countries – in which the Wall Street Journal cited, “(the FDA) rejected a therapy widely known to be highly effective, the agency’s reviewers were sending a defiant message to the medical community: The advance of biological research and development must conform to FDA institutional prerogatives rather than the other way around.” The article stated that the FDA is now demanding another round of trials that would take years and cost an extraordinary amount of money – despite the magnitude of data already compiled from previous trials – and as if to add insult to injury, these additional trials most likely will not add any more information as to answer the regulatory questions around Lemtrada’s suitability for use in MS. Does this resemble some of the eteplirsen story? Uncanny similarity – the same division that is deciding the fate of eteplirsen also rendered this rejection for Lemtrada. It makes one wonder, is it a lack of information, a case of misinformation – or as parents and patients – are we just misinformed hopefuls? After reading all the information that has been made public on eteplirsen – I for one, can state with complete confidence – given all that we know today (and at the time the 48 week data became public) as well as discussions on the clinical data with many experts clinicians and Duchenne researchers, there is enough information to render this drug safe, and a candidate for accelerated approval. I am sure that the Multiple Sclerosis community must feel the same frustration, although I can’t speak to the specific issues of that drug or its impact on MS patients other than as a fellow rare disease advocate.

The Jett Foundation, the Duchenne Alliance, and many of the parents in the Duchenne community view this safe and effective exon skipping drug as only the first step in continuing to seek out either additional drugs that can improve outcomes for Duchenne or new approaches, be that stem cells, gene therapy or other RNA based technologies that might lead to a cure or a better therapeutic approach than exon skipping. Eteplirsen is just the beginning and if we can’t get it through after so many years of research and development, so many years of trials and now over 2 years of positive 6MWT results, we may end up many years away from getting the first effective drug to help our children, knowing that the drug was within reach TODAY and the data clearly says its BOTH working and safe.

FDASIA was passed in order to help facilitate drugs for rare disease to be approved and reach patients in need faster – setting up additional criteria that allow pathways like accelerated approval, moving a drug like this through trials and to patients based on a surrogate endpoint. The FDA has a very easy choice here that either lack of understanding of the disease, lack of understanding of the technology or lack of understanding of the data has lead them to hesitate when they should be jumping in head first. The drug is safe…nothing has ever shown this level of dystrophin or this level of ongoing stability versus natural history. Our advocacy voice needs to be unified and louder. There needs to be less monopolizing of the process and differences in approach – and more focus on advocating for the fastest access to eteplirsen; accelerated approval.

Our conversation with the FDA will continue, not just as parents, but as true advocates seeking what is best for our children and challenging the FDA to make decisions based on knowledge and expertise, not influence or opinion. To that point, the Duchenne Alliance is working to provide the FDA with as much scientific information as possible – to give them every reason to find a pathway for an ethical non-placebo controlled trial and early approval of eteplirsen. We will, wherever and whenever possible, seek to provide expertise and knowledge from the scientific and medical community so that the FDA can become clearer and more confident on some of the issues that appeared to be the cause of their concern or confusion and subsequent decision on the recent reversal to accept a NDA filing by Sarepta.

We have an opportunity to make history for this disease and not only benefit the Duchenne community, but all of the other rare diseases and those patients who are also desperately seeking a cure or effective therapy. Eteplirsen is the true trial balloon by which new pathways and innovative thinking at the FDA can accelerate clinical development and get effective drugs to patients earlier when proven against an ethical, scientific and clinical risk/reward analysis. Exon skipping is one of many current and future technologies that will not allow the FDA to apply old standards, methodologies, protocols or pathways. To take these drugs forward and serve the needs of patients, especially rare disease patients with limited options, the FDA must take risk, they must innovate and they must meet the challenges and opportunities that genetic and personalized medicine are creating.

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