Replies to post #256633 on Anavex Life Sciences Corp (AVXL)

[Investor2014]

Fact!

* It took two P3 trials to get Donepezil approved
* Over 900 patients were enrolled out of which 83% completed
* Administration of both 5mg and 10mg doses in the 30-week study resulted in a statistically-significant improvement in cognition scores (ADAS-cog)

I doubt we will see A2-73 P2 trial topline results that are statistically significant. That is my opinion!

It is also my opinion that a subgroup of patients in the treatment arms might lead to a stat sig result.

You have lost me as to what we are debating, but I guess it is the difference between believing that the upcoming Anavex P2 and P2/3 trials will have stat sig topline results vs. 'only' stratification group stat sig results.

I believe a precision medicine trial selecting on the high responder patient group will be required, others think provisional approval should have occurred long time ago.

First Approval Of Eisai's Aricept For Alzheimer's

Phase III Results The approval was based on the results of two pivotal Phase III trials of donepezil which have confirmed the efficacy and tolerability of the drug in over 900 patients with mild-to-moderate AD, notes Pfizer. Both trials compared the two doses of donepezil with placebo, and consisted of either a 12-week treatment period followed by a three-week placebo washout phase, or of a 24-week treatment period followed by a six-week washout phase.

Administration of both 5mg and 10mg doses in the 30-week study resulted in a statistically-significant improvement in cognition scores (ADAS-cog) compared with patients receiving placebo at weeks 12, 18 and 24. Significant improvements were also noted for the CIBIC-Plus measure of global functioning and the mean change in MMSE scores from baseline over the 24-week period. CDR-SB scores revealed a minimal improvement for the donepezil-treated group versus a deterioration in the placebo-treated group. Clinicians rated about twice as many patients on Aricept as improved in comparison to placebo after 24 weeks of treatment. Similar significant improvements were also encountered in the 15-week study.

Greater scores were achieved on a patient-rated quality of life assessment for the 5mg group over the 10mg group, but the difference was not statistically significant. Importantly, there were no clinically-significant treatment-emergent laboratory test abnormalities, and side effects which did occur were mild and transient, lasting approximately two days and resolving on continued treatment.

Approximately 83% of patients enrolled in controlled trials completed their scheduled participation. The most common signs and symptoms leading to discontinuation were nausea, diarrhea and vomiting, occurring in 3% or fewer patients, which are part and parcel of the mechanism of action of the drug, according to Sharon Rogers, Eisai America's research chief.

[frrol]

They were marginally positive and statistically significant. So it got approved. The bar is low, which is good for us. We have lot of participants on DPZ. Hopefully we'll show improvement over baseline for them vs placebo, and also for the DPZ naive patients over baseline vs placebo.

Side note: it's so good we have blinded placebo controls. It's much more reliable than an SOC historical control. It makes even marginal stat with results that much more reliable. They're such an important trial tool.