The most nagging question for my fellow $AVXL investors is whether ANAVEX 2-73 will get approved and is there enough efficacy to get to that point?
Today (10-26-2018) at CTAD Barcelona 2018 $AVXL released information on the results of dosing patients for 148 weeks ( 2 years 10 months ). The data provided can be found on pages 17 (MMSE scores) and 16 (ADCS-ADL scores). Here, again company changed the population of the disclosure and made it to be determined by four factors given on page 12 and 13 (we call it from now on as New Cohort). Relevent is also inclusion of APOE ε4 allele incidences within the High Concentration cohort as these patient account for 40-60% AD patients and also this mutation is present in cases of extremely aggressive Alzheimer. 75% of patients present with this mutation there strengthens the case for ANAVEX 2-73as it is more representative of Alzheimer population. The criteria covered on page 12 and 13 do not give us the exact number of patient present in thus created New Cohort but if we assume that it is representative of the population to be treated then they are to be expected in Phase 2b/3 as the same criteria are applied for inclusion in the study. Also another unknown is the number of dropouts. Let’s leave these speculations alone and concentrate on the data from the presentation.
Pages 12 & 13 tell you that these are the expected results from Phase2b/3.
Let’s look at ADCS-ADL scores. The plot indicates that there was a decline of -2.0 points (average) on 80 point scale, over 3 year period. When we compare this with a plot of ADCS-ADL scores from previous post of mine, it seems that the New Cohort haven’t deteriorated from 109 weeks but again the question is which patients were included in 148 week data. The data from 109 weeks implied -2.2 points decline (average) over 109 weeks and included six patients all improving MMSE scores or slowly declining. The New Cohort stands at -2.0/2.83 years (-.70/year). Nevertheless this is what one can expect from culling the patient population by the way of genetic markers for efficacy. The Low/Medium population exhibited declines on par with placebo for ADCS-ADL scores (stand about -8.0/year ADCS-ADL).
Now time for MMSE scores, again the population has been altered to be defined with criteria for Phase 2b/3 and registered MMSE decline of -2.0 points over 148 weeks, this roughly translates into -0.7 MMSE points per year vs. natural course of -3.8/year. The Low/Medium population retained some of their scores better than average natural course patients (-2.0/y vs. -3.8/y)
If the New Cohort is representative of general Alzheimer population then (80%x80%=)64% of that population can expect that at the least in 3 years of extended meaningful lives without acute declines in cognitive and daily living abilities and lead lives almost unaffected. Also that some 40% of that population (80%x50%=) can even be improved. It is worth to note that on some level people in advanced age have natural level of declining MMSE scores. The ages of those in the trial were 55-85 so no meaningful inference can be made. As my previous posts suggested by the time of 3 years from diagnosis there remains just about ~38% people in the study (the rest deteriorated significantly) and the number of those who did not decline is about 2% of the starting population. The ADCS-ADL and MMSE data for the New Cohort suggests that more or less there are “equal weights” above and below the average line (since due to ceiling effect on improved scores number of improving scores must be greater than those declining which can go deeper below average), it might mean that my calculations on possible outcome of Phase 2b/3 were in essence correct (however crude they are) but the final check will be Phase2b/3. See Previous post predicting Phase 2b/3 results.