At that point in time there was simply correspondence between sponsor and FDA about FDA's request for more data. Nothing material, related to WB data, revealed in those docs. It all comes down to whether or not there is statistically significant difference between baseline WB and 48 week. That's the bottom line.
This is really good news for Gavin. F D A hit men would say that this is not unusual in the hx of DMD. But with exon-51 boys? Probably not. More likely with Becker's DMD.
Baseline biopsies were taken just for this type of event, if approval of the NDA was delayed due to FDA requiring additional data. At least FDA's decision isn't being delayed until 2018.
Won't it all come down to how FDA interprets the WB data? Previously, they had issue with "enhanced" images, or was that with I.F.? I think J.W. wants to avoid the Type II error and needs confirmation for her ultimate ruling. Also, if there was a Differing of Professional Opinion within FDA, this will tip the scales one way or another. There has never been established minimum dystrophin levels to confer a clinical benefit, but significance above base line should be enough for the standard of "reasonably likely" to confer a clinical benefit, not "substantial evidence" of clinical benefit, as briefing docs demanded.
Did you carefully read Sarepta's P.R.? 'The Company plans to submit data from thirteen patient biopsy samples, at baseline and Week 48, to the FDA over the coming weeks to facilitate a prompt decision on the NDA by the Agency.' What about the "coming weeks" are you misinterpreting?
He's not the only one in the camp of a positive decision this week. Today, over 5,400 June 3 $30 call contracts have been sold/bought. Big bet on some positive news this week. The clock is counting down.
From FDA's website: 'Time allotted for each presentation may be limited. If the number of registrants requesting to speak is greater than can be reasonably accommodated during the scheduled open public hearing session, FDA may conduct a lottery to determine the speakers for the scheduled open public hearing session. The contact person will notify interested persons regarding their request to speak by April 4, 2016.'
This would be most unfortunate, but likely, and could limit the number of expert DMD witnesses.
it is generally difficult to convincingly demonstrate levels of dystrophin below 10% of normal levels."
Since this is the case, and it's quite possible that levels of D could be in the 3-5% range, which would be clinically significant, how then can the FDA stand confident that 0.9% is a definitive number? It can't be.
Not sure why they would be any different than BioMarin's briefing doc questions. And if they aren't, it seems like its another drive by mugging by the FDA. I think they are trying to kill off exon-skipping as a class.
Then why was there chatter by the FDA & Srpt that the small N wasn't an insurmountable obstacle?
FDA encouraged the sponsor at the March 2013 meeting to conduct an adequately powered placebo-controlled trial of eteplirsen, stating “if it is true that eteplirsen leads to remarkable clinical benefit in even some patients, there is no doubt that a feasible placebo controlled study can be designed to demonstrate that benefit.” FDA also stated that “there is considerable variation among individual patients with regard to clinical measures and important milestones” and that data from an open-label study “may only be interpretable if a relevant objective endpoint obviously insulated from bias demonstrated compelling data that are clearly outside the know variability range for DMD.” FDA further stated that, at that time, comparison of data from Study 202 did not provide interpretable evidence of benefit “given the limitations of the open-label design for protecting against bias on effort-dependent endpoints like 6MWT.” At a July 2013 meeting with the applicant, at which the possibility of NDA filing based on dystrophin production was discussed, FDA similarly expressed reservations about natural history controls “due to the usual difficulty in showing comparability between the study populations in natural history studies,” and reiterated that 6MWT was susceptible to bias in the proposed natural history comparison.
Despite of this rebuttal, and after reviewing many other significant questions/comments within the briefing docs, it looks like an extreme long shot for AA, even given the safety profile. Maybe the best we can hope for are positive read outs on the confirmatory trials, because it seems that the FDA wants to see a larger data set.
Will help support the sp for a while, assuming whatever % of shorts cover.
The briefing docs suggest that FDA won't AA Etep, but the path forward will be: "Let's revisit this when you have more data."
One of the disturbing things in the briefing docs stated that Srpt digitally altered some of the D slides to make it appear that D production was more robust than it actually was. At that point, I bailed on all of my shares. Really hated to do that, but I'll wait until the dust settles before making a decision to get back in, or not.
Speed, you've it it out of the park....again. Great post and excellent summary. And, the most "thumbs up" I've seen in many moons - well deserved!