Dear FDA officials,
Please do not delay your decision about Sarepta’s new drug application any longer. Eteplirsen is producing dystrophin in 100% of the boys taking the medicine. Those 12 boys have been clinically stable since the dystrophin appeared, while boys with Duchenne the world over are deteriorating.
A comprehensive natural history study published in PLOS (Mazzone, January 2013) provides information on what should have happened to the Sarepta boys over the past two years. In that study, boys older than 7 who were above 350 meters in the six minute walk declined an average of 78 meters over two years. Boys seven and older who were below 350 meters declined an average of 104 meters over the two year period. These numbers do not include the 18 boys who lost ambulation during the two-year study. In both groups, the decline was much more significant in the second year compared to the first.
In contrast, the treated Sarepta boys that were still ambulatory by the time the drug took effect have experienced total stability, even improvement, over the more than two years they have spent on drug. Even more telling is the trajectory of the placebo arm. These four boys shared every risk factor for loss of ambulation: advanced age, a precipitous decline (15-20% over 36 weeks), and a baseline six minute walk of less than 330 meters). And instead of being fitted for their wheelchairs, this group of boys became stable at the exact point that dystrophin became present in their muscle fibers. As striking as it is, the distinction between the clinical progression of the boys in the Mazzone natural history study and the boys treated with eteplirsen may even be understated, as there is evidence that boys amenable to skipping exon 51 progress faster than the general Duchenne population.
Either Sarepta has lucked in to the 10 most slowly-progressing DMD patients on the planet, or it is clear that this drug is changing the course of Duchenne for these boys. Every month that both the confirmatory study and an NDA submission are delayed causes irreversible harm to all of the boys waiting for access to eteplirsen. We urge you to take swift action by accepting Sarepta’s NDA not because we want to try the drug even if it may not work, but because the data clearly show that this drug is safe and efficacious. The story is clear: dystrophin is being produced, and it is leading to disease stabilization. Every day that we fail to recognize this is a day that costs children their legs and their lives.