Anavex Life Sciences Corp (AVXL)

[sokol]

Approval of New Agents after Phase II Trials

.......The longstanding reliance on Phase III trials to prove drug efficacy and positive impact on patient survival may no longer be necessary, as early trials, particularly the expansion phase of a Phase I trial, may provide convincing evidence of a high response rate to a targeted drug in a patient population who has been poorly responsive to conventional therapy. If the new drug produces no safety signals of great concern, and if a validated biomarker for patient selection has been established and is readily available, accelerated approval may be achievable prior to completion of a randomized trial. The advantages, and potential downside, of rapid approval scenarios will be discussed in this article.

https://pubmed.ncbi.nlm.nih.gov/24451821/

Anavex has included glutamate as a biomarker it its Rett trials - See slide 30, January 2022 Anavex presentation. See also 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
September 16, 2019 07:00 ET | Source: Anavex Life Sciences Corp. 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

"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."