Answers to questions largely already known;
Committee will answer some questions in favor of eteplrisen, some not in favor.
Ball will be left in FDA's court to decide.
sailing: now that I have reread question 5, I think you are right. The reference to historically-controlled made me think they were talking about the post-hoc study with the Italian and Leuven registries - but it seems that they are not. If they aren't referring to the post-hoc, then the answer to q5 is no.
Yes - I was wondering about "neutral" versus "weaken". I chose "weaken" because the question refers to "on the persuasiveness of findings in Study 210/202". Since there appears to be no improvement at all, I assumed this question would be answered "weaken".
1. VOTE: Has the Applicant provided substantial evidence from adequate and well controlled studies that eteplirsen induces production of dystrophin to a level that is reasonably likely to predict clinical benefit?
Low levels – probably produces some clinical benefit: Answer: YES
2. VOTE: Were decisions to administer the 6-minute walk test (vs. conclusions that the patient could no longer walk) sufficiently objective and free of bias and subjective decision-making by patients, their caregivers, and/or health care professionals to allow for a valid comparison between patients in Study 201/202 and an external control group? Answer: YES
3. What is the impact of the North Star Ambulatory Assessment results on the persuasiveness of the findings in Study 201/202? Strengthen? Weaken? No effect?
4. VOTE: What is the impact of the other tests of physical performance (e.g., rise time, 10-meter run/walk) on the persuasiveness of findings in Study 201/202? Strengthen? Weaken? No effect?
5. VOTE: Do the clinical results of the single historically-controlled study (Study 201/202) provide substantial evidence (i.e., evidence from adequate and well-controlled studies or evidence from a single highly persuasive adequate and well-controlled study that is accompanied by independent findings that substantiate efficacy) that eteplirsen is effective for the treatment of DMD? Answer: YES
How can this meeting allow for serious consideration of the facts with so many participants?
Isn't it likely that the committee members have already decided how they will be voting?
Can anyone tell me if (better yet, how) Sarepta has addressed the FDA's 3 main issues per Jan 22 BD, namely:
1. "the MMRM analysis of 6 MWMT of study 201 at the end of 24 weeks shows a statistically significant difference between the placebo and the 30 mg/kg groups of eteplirsen in favor of placebo" and no statistically significant difference between placebo and 50 mg/kg was found;
2. the FDA considers that the study that showed eteplirsen's 144 m advantage over the Italian Sarepta-determined sample largely conjecture ("The open label extension with historical control is not statistically interpretable"). Reason for the FDA's conclusion as best that I can tell: (i) this comparison was not part agreed upfront - it was something Sarepta chose to put together after the fact; and (ii) Sarepta's selection of the Italian placebo sample was not something that the FDA could assure was on an apples-to-apples basis with Sarepta's treated sample;
3. the FDA considers the amount of dystrophin in muscle tissue in eteplirsen patients of 0.9% of normal (versus trace levels of 0.3% of normal in patients with DMD) to be insufficient to have any material impact on patients (10% being the threshold in the FDA's view).
If Sarepta has not addressed these issues, then:
1. how can the FDA change its approach to grant approval without losing face on the BD?
2. if the FDA does "approve", what impact would it have on Biomarin - does its drug get reconsidered for approval, or was it such dud that the FDA does not have to reconsider that one?