Anavex Life Sciences Corp (AVXL)

[Doc328]

On this subject did anyone read about ANY positive improvement coming from placebo pills in any of the RETT trials?

Trofinetide had many responders and some super responders using the RSBQ, CGI-I and RTT-DSC scales.

Looking at Figure 3A and 3B shows this. Placebo patients are in red. Visit 7 was the end of treatment visit (7-8 weeks = 54 days). As seen, about 60% of the placebo patients "responded" as measured by the parent rated RSBQ score and no patient was rated worse by the physician at visit 7 by the CGI-I scale and some patients were rated much improved (CGI = 2) by the physician, just like 2/6 of the A273 patients. The best placebo patients had a 50% reduction in the RSBQ (Fig 3A and B) after 7-8 weeks, even with the parents knowing that their child may have been on placebo. Amzingly, on teh RTT-DSC scale, the best two performing patients at 7 weeks were on placebo (Fig 3F)

The trofinetide adult study is harder to compare to the A273 adult study as Neuren only reported group data and RSBQ was not an endpoint (CGI-I was). That said, the average placebo patient was rated better by both parent and doctor.

The Neuren data has no bearing on whether A273 succeeds in Rett or not but does clearly show a placebo response, at times a strong one, in caregiver or physician scales. The glutamate data for A273 is interesting as it is objective. What is missing is knowing how much the level fluctuates on a day to day basis and whether there were differences in time of day, patient comfort or diet between baseline and week 7. We also don't know how much serum glutamate correlates to CNS glutamate.