Anavex Life Sciences Corp (AVXL)

[Doc328]

We can calculate what Anavex 273 would need to do in their primary endpoint to compare. Its also noteworthy that lecanemab was for MMSE 22-30 with CDRSB 0.5 or 1.0 and evidence of amyloid pathology while Anavex was MMSE 20-28 with evidence of amyloid pathology.

So a quick analysis of the CLARITY-AD trial (lecanemab confirmatory phase 3) cam be done with this sentence "Lecanemab treatment met the primary endpoint and reduced clinical decline on the global cognitive and functional scale, CDR-SB, compared with placebo at 18 months by 27%, which represents a treatment difference in the score change of -0.45 (p=0.00005) in the analysis of Intent-to-treat (ITT) population."

CDR-SB can be considered a combination of cognition and function allowing one test to substitute for 2 (ADAS-Cog and ADCS-ADL - or for mild patients ADCS-ADL-MCI). Any individual can change by 0.5 increments in each of the 6 scales/boxes and these are summed for CDR-SB.

Entry criteria was a CDR-SB of either 0.5 to1.0 (with the memory box being 0.5 or 1.0). So lets assume 50:50 giving an average CDR-SB of 0.75. Given the 0.45 difference between placebo and treatment leading to 27% less decline means placebo advanced by 1.67 CDR-SB 'points' and lecanemab patients by 1.22 'points'. Thus if 50:50 at entry the 18 month scores averaged 2.42 for placebo and 1.99 for treatment.

ADAS-Cog scores (secondary endpoint) were significant but they are saving measured values to present at CTAD. We can calculate expected or 'converted' values (though the actual values we will see in November will obviously take precedence to the converted scores) for comparison to A273.

With the reference below, ADAS-Cog of a 50:50 mix of CDR-SB 0.5 and 1.0 gives an entry ADAS-Cog of about 9. At 18 months, the treated group (CDR-SB 1.99) would convert to 13 on the ADAS-Cog and the placebo group (CDR-SB 2.42) would convert to about 14-15.

So using converted scores (can see actual in Nov/Dec), the treated group declined about 1.5 ADAS-Cog points less than the placebo group.


table 1 for conversion