Replies to post #423560 on Anavex Life Sciences Corp (AVXL)

[Hoskuld]

Your interpretation is incorrect (again.) 12% of PLACEBO patients could not fully up-titrate vs. 14% of 2-73 patients. Essentially no difference between sugar pill and 2-73 in terms of titration. And saying 14% could not tolerate more than 10mg is not based in fact: 14% could not tolerate 30mg. Just as 12% could not tolerate 30mg of sugar pill placebo. For safety and tolerability, these are OUTSTANDING results.

Thanks for underlining them again 12x.

[Doc328]

I'm not sure if Rett had titration but PDD did.

However the 132-patient PDD p2 trial didn’t report any tolerability issues with neither 30 nor 50mg groups.

That's not correct, similar dropout rates were seen in the 14 week PDD trial compared to the longer AD trial

From the 2020 CTAD PDD presentation:
- Subjects with at least one TEAE leading to study discontinuation in the maintenance phase were
4.9% in the active cohort versus 4.7% receiving placebo
- The majority of TEAEs were observed during up-titration of which (light) dizziness (10.2% for active
drug versus 2.3% placebo) leading to study discontinuation while typical adverse effects seen in
marketed CNS drugs were not observed

So in PDD, there were more problems with tolerability during up-titration than maintenance and in AD the opposite was seen.

The 50 mg cohort for PDD had about 15% dropout (6 of 44 patients) during the 14 week trial compared to 5 of 44 patients for 30 mg and only 3 of 44 for placebo (see the first column third section in https://www.arianapharma.com/wp-content/uploads/2022/03/79bcf7_ff6b864593fb4418ab306474dd535d35.pdf)

I don't know if Rett had titration. Rett Avatar had 2 dropouts out of the 20 treated patients and 0 dropouts out of the 13 placebo patients over the 7 week trial.