Anavex Life Sciences Corp (AVXL)

[sokol]

The significance of the recent peer reviewed publication may be that it is another piece of evidence, among the growing body of evidence, to apply for early approval of AVXL 2-73: Here are some excerpts from this publication entitled: A precision medicine framework using artificial intelligence for the identification and confirmation of genomic biomarkers of response to an Alzheimer's disease therapy: Analysis of the blarcamesine (ANAVEX2-73) Phase 2a clinical study


This paper begins with an introduction:


"Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by loss of memory and other cognitive functions, leading to interference in daily life activities. At present, no pharmacological treatment has been shown to alter progression of the disease1. Heterogeneity of the AD patient population2, 3 and lack of objective efficacy measures or predictive biomarkers of response4 contribute to this limitation. Sigma-1 receptor (SIGMAR1), a modulator of calcium homeostasis and mitochondrial function,5 is a new target relevant to AD.6 SIGMAR1 activation has been shown to reduce key pathophysiological processes in AD including hyperphosphorylation of tau,7 neuroprotection,7 and oxidative stress.7, 8 Activation of SIGMAR1 also leads to increase in autophagic flux in human cells and in vivo.9"


Later this is stated:


"Randomized clinical trials in AD have been challenged by two major hurdles:


Variability in the assessment of efficacy based on clinical evaluation of cognitive, behavioral, and functional changes over time with inherently noisy tests or questionnaires. Robust links have yet to be established between clinical outcomes and reproducible neuroimaging/fluid-based biomarkers. The uncertainty in the values measured by these endpoints adds to the uncertainty in the determination of therapeutic efficacy.


Heterogeneity of AD, based on neurobehavioral features, inheritance (familial or sporadic) and other genetic characteristics, time course of progression, age of onset, pathological and other features, which have been discussed at length.


This observed heterogeneity is also seen in other therapeutic areas such as oncology. In oncology, multiple small, open-label clinical trials are run in which a broad range of biomarker candidates are identified and hypotheses generated and tested iteratively, serving as foundation for the design of follow-up controlled studies. Crizotinib is a good example of accelerated approval in oncology following an open-label Phase 1a study, where a novel biomarker (ALK+) was first identified based on 2 of 11 patients with non-small cell lung cancer enrolled in a Phase 1 dose escalation trial.54 The biomarker was validated through an amended Phase 2a study including 19 patients, with 10 out of 19 patients being labeled as responders, which ultimately led to a preliminary drug registration. Subsequently, a confirmatory trial enrolled 82 ALK+ patients and showed 57% partial response and 1% complete response. Unbiased and unsupervised data analytics methods such as the KEM platform may be ideal tools to streamline this type of discovery process. As such, they provide systematic iterative precision medicine tools for drug development, suitable as much to AD as to oncology. The search for alternative druggable targets for AD is becoming a priority, and SIGMAR1 targeted by blarcamesine (ANAVEX2-73) may be an important drug target to maintain cellular homeostasis, delay or halt neurodegeneration, and/or enhance synaptic compensatory responses, as suggested by experimental studies."


The following is something I posted early this year or at the end of last year:


It appears that 2020 may be the big year for Anavex and AVXL 2-73!


AVXL 2-73's Chances of Approval:


Numerous Scientific Publications are Supportive for AVXL 2-73


AVXL 2-73 Animal Studies Confirm the Scienific Liturature


AVXL 2-73 Human Clinical Trials Confirm the Science and Show Promise


Real World Evidence is Supportive


The Anavex and Ariana Comparitave Study of Patients from Anavex’s AD trials and AD Patients from the ADNI Data Base is Positive.


As of the end of 2019, around 400 or so patients will have participated in AVXL 2-73 clinical trials for AD, PDD and Rett. Some of those patients are placebo patients. It may be that this time next year there will be 600 or more patients participating in Anavex’s clinical trials. However, Anavex may be expanding the clinical trials. PDD clinical trial results may be available mid 2020.


Slides from Anavex's most recent presentation:


“FDA’s new Real World Evidence Program Likely to have a Profound Impact on the Biopharma Industry” was the first slide in the most recent Anavex presentation wherein Anavex and Ariana did a comparitave placebo mimic study using patients from Anavex’s AD trials and patients from the ADNI data base.


The slide entitled “Use of Real World Evidence in Regulatory Settings is Gaining Momentum” from Anavex’s recent presentation mentions one drug, Blinatumomab, approved by the FDA with supporing Real World Evidence. That slide lists reasons and benefits for using Real World Evidence together with results from clinical trials:


• Collection of real-world data is not new

• May provide access to patients that may not have been considered in a clinical trial

• Ethical question of unnecessarily exposing patients to placebo

• Reducing size, duration and costs of trials

• Accelerating regulatory path


See the slide "ANAVEX®2-73 Selective Sigma-1 Receptor (SIGMAR1) Agonist Demonstrated Improved MMSE1 and ADCS-ADL2 Scores in Phase 2a AD Study through 148 Weeks" If this and other type of improvement (such as improved gut microbiota*, etc.) continues into 2020 with significant numbers of AVXL 2-73 treated patients, 2020 could be the big year for Anavex.


* "Communication between gut microbiota and the brain has been shown to be a critical requirement of a healthy brain function. The reduction in gut microbiota diversity has become one of the hallmarks of aging, and disturbances in its composition are associated with several age-related neurological conditions, including Alzheimer’s disease....”
Giau, V.V.; Wu, S.Y.; Jamerlan, A.; An, S.S.A.; Kim, S.; Hulme, J. Gut Microbiota and Their Neuroinflammatory Implications in Alzheimer’s Disease. Nutrients 2018, 10,
1765

https://www.anavex.com/anavex-life-sciences-presents-new-clinical-data-identifying-gut-microbiota-biomarkers-associated-with-improved-clinical-response-in-patients-treated-with-anavex2-73-at-2019-alzheimers-a/


And, of course, since my late 2019 - early 2020 post additional scientific support for AVXL 2-73 has surfaced, including articles about autophagy, etc.


Lastly, I do not think anyone can accurately predict the date for approval or disapproval of AVXL 2-73 despite my statement that 2020 may be the big year for AVXL 2-73 although I do think this year we will receive big news from the clinical trials.