Academics Back Sarepta’s Eteplirsen for Duchenne
Some 36 university professors from UCLA and other institutions in the U.S., Canada, and Australia say that the findings of a clinical trial of Sarepta’s eteplirsen to treat Duchenne muscular dystrophy “are sufficiently robust to support the proposed mechanism of action of eteplirsen, to provide a plausible explanation for the relative gain in function observed within the treatment group and serve to bolster confidence that there is a positive treatment effect.” In a recent letter to FDA and its Peripheral and Central Nervous System Advisory Committee, the experts acknowledge that as is the case for all small studies, there is some uncertainty as to whether the trial findings will accurately represent subsequent observations in larger study groups. “However,” they write, “the only way to address that uncertainty is to expose more individuals to the drug and assess efficacy on the overall amenable population over even longer periods of time. The excellent safety profile of eteplirsen makes this strategy reasonable.”
The letter says that an FDA briefing document released in advance of a 1/22 advisory committee meeting that was postponed questioned the value of the trial’s external control group, contained “some scientifically questionable comparisons, and in some instances has errors that may lead to a false perception that there is little evidence that eteplirsen has any effect at slowing the progression of DMD.” The writers provide information from their clinical experience to address each of those issues.
They conclude that “it would be dubiously ethical to veer from the currently recommended study path at this point. In keeping with the criteria imposed by FDASIA (the FDA Safety and Innovation Act) for accelerated approval for rare disease with unmet need, we conclude that the aggregate date described in the briefing documents are providing substantial evidence of efficacy and use in the greater population of boys amenable to exon 51 skipping is appropriate. We suggest that the most scientifically robust way forward and the most ethical choice for the Duchenne community is in the context of an accelerated approval followed by a confirmatory trial.”