Ann: Plans for Phase 3 trial in Rett syndrome, page-40

I think that one concern for the market, as already expressed here on the other thread, is that a three month trial doesn’t seem to be as robust as expected.

As lilypily pointed out on the other thread, we saw previously that the patient response increased with time. Intuitively, one would expect that a longer trial should demonstrate even better outcomes and hence, produce stronger data.

The previous Phase 2 paediatric trial was often referred to as a 3 month trial, and the registered clinical trial details show it had a time frame, through to study completion, of 11 weeks. However the actual dosing period, as shown by the trial result graphs below, was just 6 weeks.

I contacted the Company to ask if it was intended that the 3 month Phase 3 trial would be similar in time frames to the Phase 2 paediatric trial or if it was intended in this new trial to provide a dosing period of 3 months (hence, 12 weeks dosing v 6 weeks dosing – i.e. double the duration). The Company has confirmed that “the direct comparison is 12 weeks randomized placebo-controlled dosing in Phase 3 versus 6 weeks in Phase 2 (i.e. twice the length).” I am very relieved that that is the case.

I also asked if the adjustment to the trial duration had been agreed to by the FDA and if an SPA had been obtained . I was informed that the FDA has agreed but that ACADIA had not sought an SPA and neither had NEU previously. This is apparently not unusual for orphan drugs as an SPA “can actually be unhelpful since it boxes the agency into a binary legal position rather than considering all the data submitted.”