Moving forward, faster

Posted by: Christine McSherry on September 23, 2013




Friday, GlaxoSmithKline (GSK) and Prosensa today announced that GSK’s Phase III clinical study of drisapersen, for the treatment of Duchenne Muscular Dystrophy (DMD) patients with an amenable mutation, did not meet the primary endpoint of a statistically significant improvement in the 6 Minute Walking Distance (6MWD) test compared to placebo.  The entire Duchenne community, and many in the rare disease community (those who were hoping that this technology would benefit their disorder someday) were devastated. Families who have given years of their lives – boys who have sacrificed so much – from birthday parties, days at school to pieces of muscle used for biopsy, no longer will be given a drug that for many of us, held so much promise. Albeit we all know that when we subject our children and ourselves to a human trial – that is exactly what it is, a trial…but that doesn’t make it hurt any less. I would imagine that it feels like being diagnosed with a lethal disorder, all over again, and that is something no one should have to endure a second time.

And yes, the community will pick itself back up – and continue the fight.  This is a community that is full of active parents and organizations, parents who are able to turn their passion into action and clearly their action has resulted in a robust landscape of potential therapeutics.


The challenge will be to turn this time of grief into a concerted effort – to harness the sadness and direct toward what is left, the collateral damage of a failed phase 3 into something that is positive.


Sarepta’s lead compound, eteplirsen has demonstrated benefit without any side effects. Eteplirsen is effective in those who would be amenable to skipping exon 51. Last March, in a meeting hosted in London, the company proposed a clear and direct plan to address the additional subgroups of exons in Duchenne. Parents who attended the meeting asked Sarepta what they needed to get there – the answer might surprise many…all they needed was advocacy from the community.


For the last year, that is what Jenn McNary, Mindy Leffler and myself have been doing.  We have met with the FDA numerous times to discuss “permissible risk”, clinical trial design in rare disease, challenges that patients face, we even brought videos of kids improving on the drug – we email them, call them and blog about them – we have shown them the natural history of Duchenne, that boys who start to decline – don’t get better, ever.  We have let them know that we fully support Sarepta’s decision to seek accelerated approval. Like all parents of those with Duchenne, each of our stories were unique, but the same  - our boys were dying and we were trying to save them.  At the time, Mindy’s story was slightly less urgent than mine or Jenn’s because her son was on drug; Aidan was on drisapersen.


Now, today – there is an added level of urgency in our plea.  We can not sustain any additional delays. There are ways to our means – unprecedented, maybe – but there is a way.


1.  Transparency – The dystrophin data from GSK/Prosensa should be made available to help move exon skipping technology along – is there any evidence of correlation between dystrophin production and the walk test?  If there is, this evidence could be an additional argument for accelerated approval of eteplirsen. Regardless, the data belongs to the community.


2.  No Placebo – These boys, like all others amenable to exon skipping – can not be subject to another placebo based trial. Ethically, knowing that there is a compound, that can be dosed high enough – that is 100% efficacious and 100% safe, knowing all that we know today about eteplirsen – all boys should be eligible for drug and not be used in a placebo trial – as quickly as possible.


3. Accelerated Approval – The discussion around the 4th biopsy request should be met with a stiff agreement by the parents of the children in the trial. The children should not be subject to an additional biopsy, however, if the parents choose to agree – there needs to be a clear and direct benefit to the community, it needs to be understood that if the data continues to show evidence of dystrophin, and the boys in the trial continue to be stable – that dystrophin as a surrogate marker should be accepted, and therefore accelerated approval granted.


We must stand together and demand what is right for our community – this is not about a “drug company” – this is about the disease, Duchenne and what is fastest path to get therapeutics out to this generation of those affected – we need to change the landscape of industry, regulators and patients for the greater good.


Jenn, Mindy and myself will be returning to the FDA very soon – this time, they will know that Mindy no longer has a safety net. Aidan, like Jett and Austin, is dying.





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