Sarepta Therapeutics (SRPT) continues to tumble in premarket trading — shares are now down more than 45%.
The FDA came down particularly hard on dystrophin's ability to predict clinical benefit: "The disconnect between increased expression of dystrophin and clinical efficacy for drisapersen ... raises considerable doubt about the biomarker," the regulator says, adding that "the quantity of dystrophin that might be necessary to be considered reasonably likely to predict clinical benefit is even less clear."
Also questioned is the 6MWT: "Recent natural history data in DMD indicate that a baseline 6MWT e350 meters predicts continued general stability for such patients, not the 75- to 83-meter yearly decline [SRPT] suggests in the meeting package." Even worse: "The expected variability of 6MWT values appears sufficient to explain differences between arms on which the post-hoc analysis was based."
Bottom line: The FDA "believes a placebo-controlled trial would be the most likely method for developing interpretable evidence of efficacy for eteplirsen, because efficacy endpoints in DMD are effort-dependent and susceptible to bias." (PR)