Here is slide 24 from the Jan 2018 presentation wit the full AE info.
98% of all AEs were mild or moderate and reversible with 76% being Grade 1
Grade 1 AEs require no intervention!
AE profile similar to that of healthy volunteer Phase 1 data
based on this I find it unlikely that Safety and Tolerability is a major issue and, as you probably have heard, Missling tends to highlight the safety of the drug also supported by the bulk of Sig-1 research.
The company’s task now is to find a standard minimum dose that is strong enough to get patients to at least 4 ng/mL plasma level, without inducing these side effects.
The above quote in the light of the data published can hardly be taken to infer that patients broadly struggled with dosage levels therefore making it hard to reach 4ng/mL.
I continue to content, perhaps wrongly, that patients were kept in 4 groups pre-assigned to 10m, 20mg, 30mg and 50mg respectively throughout Part B. The population dosing and response data thus gathered is perfect for finding the standard minimum dose to use in future trials. That dose will likely be adjusted for age/body weight for the young participants in the Rett trial. Thus, it just means that the company needs to find the standard minimum dose, not the standard maximum dose that will get the most patients into the therapeutic window.
None of us knows what feedback the FDA had on the Rett IND, but anyone is free to promote that it was something approaching a doomsday scenario.
AI
