Replies to post #92751 on Anavex Life Sciences Corp (AVXL)

[OFP]

Hi Seventhwave,

1. What are your thoughts on the strong 6 responders?

I am not overly impressed with partial revelation of data. In addition 2 of the group had the bulk of their improvement in the first 5 weeks (a total of 24 days of treatment in that timespan) with gains of 4 and 6 points followed by another point or so gain (if I remember correctly).

2. Do any Alz drug trials see such cohorts sustain outperformance (into 57 weeks) beyond initial phases of testing that may be placebo effect related?

I think it was Flash1 who provided a reference and made the point that this proportion was not out of line. I have the reference but need to run...check his posts.

gotta run...will come back to other questions

[F1ash]

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"1. What are your thoughts on the strong 6 responders?
2. Do any Alz drug trials see such cohorts sustain outperformance (into 57 weeks) beyond initial phases of testing that may be placebo effect related?
3. Have any Alz drug trials exhibited an upturn in MMSE or ADCS-ADL for the entire study group, not just for a cohort.
4. While MMSE is the most reliable measure acknowledged by peers, is it fair to say it FULLY/COMPREHENSIVELY captures and reflects changes & progression and therefore qualitative reporting of benefits is redundant and shouldn't be considered by the FDA? "
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#1.... Consider reading this study.

"Variability in Annual Mini-Mental State Examination Score in Patients With Probable Alzheimer Disease"

http://jamanetwork.com/journals/jamaneurology/fullarticle/775209


#2....The attached graph shows dots that represent the changes in test scores. Notice how many participants actually showed an increase even after 3 years. (It's "Figure 3" if the first link does not work)

http://jamanetwork.com/data/Journals/NEUR/6482/noc8161f3.png

http://jamanetwork.com/journals/jamaneurology/fullarticle/775209

#3.... When you say "The entire study group" do you mean the 25 who are left or the 32 who started the trial? No one seems to know or even care how those individuals are represented in the graphs. How that data is represented in the graph could make significant changes in its interpretation. Traditional dropout rates in the placebo arms of Alzheimer's trials are.....
"•In RCTs for Alzheimer's disease one out of fifteen patients treated with placebo drops out because of AEs." ,

but here 5 patients dropped out so that's double the expected rate. Why did they drop out?

http://www.jns-journal.com/article/S0022-510X(15)00311-1/abstract

#4...."Conclusions Although the Mini-Mental State Examination is a useful screening instrument to assess level of cognitive function, it has limited value in measuring the progression of Alzheimer disease in individual patients for periods less than 3 years because of a large measurement error and substantial variation in change in annual score"



What are your thoughts after reading the studies I referenced?

[OFP]

3. Have any Alz drug trials exhibited an upturn in MMSE or ADCS-ADL for the entire study group, not just for a cohort.

I don't know of any even with proven treatments. Certainly none for indefinite time frames because nothing exists that has been shown (or even close) to reverse AD.

4. While MMSE is the most reliable measure acknowledged by peers, is it fair to say it FULLY/COMPREHENSIVELY captures and reflects changes & progression and therefore qualitative reporting of benefits is redundant and shouldn't be considered by the FDA?

First, I'm not sure I agree or know that MMSE is the best measure, just that it was the most important one that was available in this study. Qualitative reporting is fine at this stage..but not very useful or weighed very heavily in terms of approval decisions.

5. Are your statements setting expectations, implicitly assuming the entire study group was optimally dosed to full strength?

I'm not sure what expections I'm setting. I'm merely commenting on expectations/results AVXL is describing in patients dosed as they were dosed. I can't say how "full strength" dosing would change things.

We know Anavex has dropped their claims of synergy with DPZ and that DPZ may be a hindrance, not to mention sup-optimal dosages of 2-73 among patients.

I didn't know this..in fact I'm a bit surprised if true. I think one of the bigger disappointments of this trial is that they didn't show an indication of possible synergy as per the mouse data but I don't think a non-placebo trial can really disprove it and I'd expect they will need to have significant numbers of patients on DZP for their subsequent trials so I consider it an open (though now somewhat more doubtful) proposition.

Are you a prospective investor - just curious as to where you are coming from.

Prospective only at this point. See my preceding post for more specifics.