Replies to post #432687 on Anavex Life Sciences Corp (AVXL)

[Investor2014]

I assume you would have read the full article before articulating you views?

Plasma Aß42/40
It was first reported in 1995 that Aß42 concentration was significantly reduced in the CSF of patients with AD dementia.45 Subsequent studies confirmed this finding and demonstrated that lower CSF Aß42 was associated with brain amyloid pathology, likely due to sequestration of Aß42 into amyloid plaques.46,47,48 It was also found that the CSF Aß42/40 corresponds better than Aß42 to brain amyloid pathology owing to the normalization effect of Aß40, which essentially controls for interindividual differences in the production of Aß peptides in the brain.49 Similar effects were found in plasma several years ago, when technological advancements enabled precise measurement of Aß40 and Aß42 at a much lower abundance and in a much more complex matrix.50,51,52,53,54,55,56 While individuals with amyloid pathology have reductions in CSF Aß42/Aß40 of approximately 50%, reduction in plasma Aß42/Aß40 are only 10%–15%.39,50,52,57 The smaller effect size could be due to peripheral production of Aß that is not impacted by AD pathophysiology, thus diluting brain-derived Aß and reducing the dynamic range of this measure. Analysis of discordant cases among fluid (CSF and plasma) amyloid biomarkers, amyloid PET, and results of longitudinal studies suggests that changes in CSF and plasma amyloid may be detected earlier than the typical detection threshold for amyloid PET.52,58 Various assays for Aß42/40 can be divided into two broad categories: immunoassay based vs. mass spectrometry (MS) based, which have been previously reviewed in depth.57,59,60

I would say that since Anavex is doing both BBBM and CFS measures of Aß42 and Aß40, this paper is promissing in that the Aß42/Aß40 ratio is a marker near implementation, although for diagnostics/prognostics rather that so far as a surrogate biomarker indicating change in plaque load. Still PET scan is the accepted surrogate, but given how sensitive well and correlated Aß42/Aß40 especially from CFS is to the PET plaque reference and the very low p-values of change Anavex reported, it could bode well for Anavex Accelerated Approval despite being based on the FDA accepting a new surrogate endpoint.

Let's see, that is if you are not too busy and preoccupied with your conspiracy theories.