Replies to post #446482 on Anavex Life Sciences Corp (AVXL)

[nidan7500]

bas2020

t would be a true disappointment and failure if the endpoints missed an expectedly "normal" placebo response of little to no improvement. If the placebo response was "normal", blarcamesine would've clearly exceeded in meeting endpoints and the trial would've been a resounding success.

Obviously, that didn't happen. Instead, the trial got hit with some unfortunate bad luck with extraordinary placebo scores. However, it's not the first time a Rett trial has experienced this... and the reasons behind it are quite plausible. It's not a true placebo effect with the patient, where the patient realizes s/he is taking a drug and believes it's helping him/her. Rather, it's one that's expressed and influenced by the parents/caregiver... and that positive "hope" and belief are conveyed to other Rett parents, as well as the reviewers. It's rather normal for this "bias" to happen... more so with pediatric patients than with aging AD patients.

It's not the first time the FDA has experienced this phenomena... and is why they frequently approve a drug in these circumstances, especially a safe drug. They review the entire package of trial data, OLE and REW information in the approval process... not just the p-values.

Not concerned at all about the prospects of approval for Rett... and AD.

Great-refreshing-evaluation and post...thanks, we needed that assurance. Let's face it...this is very thin ICE w/many worried onlookers. The criteria of not getting (even a little bit) wet is a worry. Thanks for the value added reasoning.

[abew4me]

Quote: "It's not the first time the FDA has experienced this phenomena... and is why they frequently approve a drug in these circumstances, especially a safe drug. They review the entire package of trial data, OLE and REW information in the approval process... not just the p-values."

Bas2020...although I agree with the premise of your statement, can you give us a few examples for comparison?

Thanks.

abe

[Schmiggins]

Correct. I mentioned this idea last week. I think you're right that the wild placebo effect will be discounted by the FDA. My original posting of the idea is below. That, plus the patent today on our drug's effect on the defective gene's downstream repercussions - if measured, as I believe we have done - will likely lead to an approval. Add on the fact that Bas2020 and FranzKafka have laid out the newish FDA approval approach (as in the Sarepta case), and the fact that there is no LAW saying p value of .05 is a hard and fast requirement....and I think we're sit pretty well at this point for an approval.

The "very high placebo effect" repost. (A two-fold placebo effect, by the way: both in the patient and in the observer/recorders of outcomes.)

"Steady: "Placebo subjects don't get the drug so how does 2-73 kick it up a notch?"

Answer: Both cohorts (drugged and placebo) will evidence the placebo effect. Our drugged cohort beat the placebo cohort by 50%. My little theory is that the Sigmar1 receptor or chaperone we enhance is actually what's behind placebo effects generally. By kicking up Sigmar1 we are kicking up the mechanism behind placebo effects - which have real bodily effects, its not just perception*.

* Although in this trial, the measurements are subjective and so you get an additional "placebo effect" outside the bodily placebo effects. I could bet the subjective recorders of what they are seeing are also "seeing what they want to see" (positive improvement), try as they might to be objective. So we saw a placebo effect (likely the same in both cohorts) of around 8 points, which is higher than the norm and my thought is maybe 3 points of that is due to the subjective nature of the person recording what they "see".

So, I suppose you could subtract those 3 points from both cohort's improvements. So the placebo group would then show a 5 point improvement and the drugged cohort a 9 point improvement. Which actually would then give us our "statistically significant" improvement number after all !!"