Disappointed by the call:
1) It seems now that they clearly focus on odds ratios instead of changes in ADAS-Cog and ADAS-ADL. Surprised that they now consider the raw change in ADAS-Cog as just an additional result.
2) Given the above and that they did not present the change in ADAS-ADL, I consider they missed that endpoint. This might explain overemphasizing the odds ratios as the main outcome of the trial. Also, I think that the PR headlines about meeting the endpoints were referring to the odds ratio results. This is unfortunate and a gift to AF and the shorts as they practically changed the endpoints again.
3) The odds ratio comparisons with aducanumab were meaningless due to the use of a different threshold between the two studies.
4) I might have missed that, but did they say anything about differentiating between the 30mg and 50mg cohorts?
5) I do not know how to characterize Missling's questions to the experts.
Given the above, my opinion and apparently that of both of the experts in the call is that a new P3 trial will be likely needed. Not sure if the regulators will be convinced based on the safety profile and the convenience of oral administration to approve overlooking the limited efficacy evidence. On the positive side, Missling said he is committed to progressing the discussions with the regulators aggressively and applying for a CMA. Maybe the full dataset will provide stronger evidence for their application.
