Anavex Life Sciences Corp (AVXL)

[XenaLives]

"Very strong" may not be good enough

Note that Kaufmann participated in designing the study and writing the paper.

He's Anavex CMO now.

Both efficacy endpoints, the Rett Syndrome Behaviour Questionnaire (RSBQ) and the Clinical Global Impression – Improvement (CGI-I) showed significant improvement with respect to baseline after 7 weeks of treatment. The RSBQ Total average scores improved from 50 to 34 points (2-tailed Wilcoxon signed rank test, p = 0.027) and the CGI-I scores were positively correlated with RSBQ Total scores at 7 weeks (2-tailed Spearman’s rho = 0.956, p = 0.003).

Supporting the clinical assessments, plasma levels of the biomarker Glutamate also decreased significantly (Week 0 vs. Week 7; 2-tailed Wilcoxon signed rank test, p = 0.046) and levels of Glutamate at Week 7 were directly correlated with CGI-I scores at Week 7 (2-tailed Spearman’s rho = 0.837, p = 0.038) with greater decreases in Glutamate associated with greater improvement in these efficacy scores. Glutamate is the main excitatory neurotransmitter in the brain and is known to be higher in patients with Rett syndrome compared to healthy subjects in the brain, as measured by magnetic resonance imaging spectroscopy (MRS), as well as in cerebrospinal fluid (CSF) and blood plasma.

Additionally, the magnitude of GABA change was inversely correlated with the magnitude of decrease in RSBQ Total scores (2-tailed Spearman’s rho = -0.812, p = 0.050) and GABA changes demonstrated an inverse correlation of the magnitude of Glutamate changes (2-tailed Spearman’s rho = -0.829, p = 0.042).
GABA is the main inhibitory neurotransmitter in the brain, known to be deficient in animal models of Rett syndrome. Excitatory-inhibitory imbalances postulated in many neurologic disorders, including Rett syndrome, have been linked to imbalances between Glutamate and GABA1,2.

https://www.globenewswire.com/news-release/2019/09/16/1915810/0/en/Anavex-Life-Sciences-Announces-Preliminary-Clinical-Efficacy-Data-of-its-U-S-Phase-2-Clinical-Trial-of-ANAVEX-2-73-in-Patients-with-Rett-Syndrome.html

No mention of GABA for Neuren, why?

Among the 3 outcome measures with p < 0.05, the magnitude of effect (% change of the median score) for RTT-DSC was 15% (vs 5% for placebo) and the magnitude of effect (% change of the mean score) for RSBQ was 16% (vs 6% for placebo). For CGI-I, the mean was 3.0 for the 200 mg/kg bid group and was 3.5 for placebo, with more than 20% of participants scoring a 2, “much improved,” compared with less than 5% of those on placebo. Cohen d effect sizes were -0.645 for CGI-I, -0.247 for the RTT-DSC, and -0.487 for the RSBQ total.

https://n.neurology.org/content/92/16/e1912