There is Nothing like Blarcamesine in the Alzheimer’s Drug Search $AVXL

Do not trade on this post since 4 billion years of evolution and God himself might be against my conclusions!

 

Seekingalpha.com had on 12 04 2019 this press release.

Seeking alpha pree release 12-4-2019

The only problem with this press release is that it is warmed up info already given by $AVXL when it for the first time revealed the 148 weeks data adjusted for Precision Medicine a.k.a. genetic markers.  The following graph can be seen on page 20 of ANAVEX Corporate Presentation from October 2019, the first publication even predates this.

ANAVEX A2-73 Phase 2a 148 weeks MMSE score 20p Corporate Presentation 2019 OCt

Following trend lines are shown:

  • Blarcamesine High Concentration adjusted for genetic markers MMSE scores ~ y=-1.1*(x/52) (for this graph) (x in weeks)
  • Blarcamesine Low and Medium Concentration adjusted for genetic markers MMSE scores ~ y=-4.4*(x/52)
  • Blarcamesine High Concentration decline accelerates with the duration of the dosing, by data points, not the trend. The rate of which between 96 weeks and 148 weeks (52 weeks difference) is y=-1.3*(x/52) (x is weeks).
  • Better fit to Blarcamesine High Concentration decline data points can be given by quadratic equation y=-.21632*x^2+.025*x+20 (x in years).
  • Ultimately, it is entirely possible that ADNI Placebo might have an accelerated decline curve as well since Blarcamesine Low Medium Concentration might be affected by the drug.
  • At this time we have no further information on ADNI Placebo arm than the assumed linear decline of y=-4.4*x+20 (x in years) (2 days before the presentation)

These numbers are about the same as in the Press Release.  Our goal at first is to present the data extrapolated to 6 years. For both ADNI placebo and Blarcamesine.  The case of acceleration in the deterioration rate after 96 weeks can be presented by extrapolating the rate between years 2 and 3 into next year ( year 4).

MMSE SCORE for A2-73 woth Placebo by ADNI CTAD 2019as of 12-06-2019 copy

  • What can be seen here:
  • ADNI Placebo (yellow line) for the first 2 years declines -4.4 points. The extrapolation (black line) into an additional 4 years gives the final score of  6.8. (y=-4.4*x+20)
  • The extrapolation of Blarcamesine y=-1.1*x+20 gives a final score at 16.7 (magenta line)
  • Extrapolating Blarcamesine decline till year 6 and using the rate of decline from the last data points as specified on the graph from the corporate presentation, gives a score of 13.2.

Word of caution; the decline of Alzheimer’s patients over time can be accelerating. 6 years of placebo Alzheimer

(the legend says “probability” but it should say “population fitting given decline”). One can see that with time number of patients is dwindling.  This image gives the idea about the rapid decline in the number of patients whose decline can be keeping the average for the group higher (MMSE score).  At this point, 2 days before the presentation we have no data to present any conclusion on this. The assumption then is that the decline is linear but the decline of Blarcamesine patients follows the worst-case scenario:

Blarcamesine patient declining with accelerating rate and ADNI patient with a linear steady rate.

 

AVXL CTAD 2019 12-05-2019

  • We assuming that decline starts from MMSE score 20
  • Blarcamesine High Concentration Adjusted data points (4 data points in blue) are well fitted by the yellow curve (the quadratic equation)
  • The ADNI Placebo is showing a steady rate linear decline in scores. In the real world, that might not be the case.

To evaluate the efficacy of Blarcamesine vs. ADNI Placebo we looked at

  • The advantage in retained MMSE points by Blarcamesine patients over ADNI Placebo
  • The delay in years in the score for Blarcamesine patients over ADNI Placebo
  • The relative performance of Blarcamesine in terms of declining ADNI Placebo score.

AVXL CTAD 2019 Efficacy 12-5-2019

  • The Green Bar: the MMSE score difference grows till it reaches almost 6 points at 5 years into treatment
  • The Yellow Bar:  Years need for average Blarcamesine patient to reach deterioration of ADNI Placebo patient; starts at 3.5 years and steadily declines as shown.
  • The Blue Bar: The MMSE score difference between arms as a percentage of the current score of the ADNI Placebo patient; Steadily increasing.

In general, the age of diagnosis determines the average life expectancy after diagnosis; For a 65-year-old patient that can be 8.3 years, for a 90-year-old patient this is 3.4 years.  Assuming that at the score of 10 MMSE points patient is hospitalized; Blarcamesine buys additional 3 years out of an institution for a 65-year-old patient.  That is notwithstanding the benefit of retaining a person’s cognitive abilities.

Conclusions;

  •  In the first 2 years, Blarcamesine patients are expected to decline 4 times slower than placebo patients.
  • If the extrapolations have any predictive value; Blarcamesine keeps the patients, in 6 years, from reaching the point of being classified as “Severe” and institutionalized.
  • Presented data on Blarcamesine Advantage is the WORST CASE SCENARIO; ADNI Placebo arm is declining in a linear fashion, that might no be the case in the real world.
  • Performance of Blarcamesine over Standard of Care is about six times greater than that of Donepezil.

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