Replies to post #305373 on Anavex Life Sciences Corp (AVXL)

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Michael J. Fox and his foundation on board actively supportive in addition to granting money?

Michael J Fox.org/grant/evaluation-anavex2-73-blarcamesine-participants-parkinsons-disease

Evaluation of ANAVEX2-73 (blarcamesine) in Participants with Parkinson’s Disease

We are testing ANAVEX2-73 (also known as blarcamesine), which previous research has shown helps improve behaviors as well as normalizes biochemical changes in a Parkinson’s disease animal model (6OHDA, which was supported by MJFF). In 132 patients with Parkinson’s disease dementia, the drug significantly improved cognitive function and memory as well as REM sleep. This includes complex cognitive tasks that impact quality of life such as making a choice between similar objects and remembering daily personal experiences, which could be impaired in Parkinson’s disease. In patients with Alzheimer’s disease a Phase 2a trial demonstrated a concentration dependent response in both cognition (MMSE) and function (ADCS-ADL) over 148 weeks (longer than 3 years).

The drug works by activating the Sigma-1 receptor protein in the brain. This protein helps brain cells stay healthy by reducing the effects of certain kinds of stress, preventing toxic proteins from building up in brain cells, and possibly protecting brain cells in other ways. This study is an important step in discovering if activating this protein will slow or reverse damage to brain cells and help them work normally again, thereby slowing or stopping Parkinson's progression.

Hypothesis:
We want to know if this new drug, ANAVEX2-73 (blarcamesine) can safely travel through the body to the final destination in parts of the brain most affected by Parkinson’s disease, which will help us determine if this new drug can help people with Parkinson’s disease.

Study Design:
In this study, researchers will give ANAVEX2-73 (blarcamesine) to up to 24 patients with Parkinson’s disease and healthy volunteers. The drug will be bound to a special tag or marker which will allow us to visualize the drug as it moves through the body to brain, using a medical imaging tool called Positron Emission Tomography (PET).

The researchers will also take blood samples from patients to learn about how the drug breaks down in the body to make sure it is safe and has minimal side effects.

Impact on Diagnosis/Treatment of Parkinson’s Disease:
This project will help us understand if this drug can safely make its way to the brain cells that are affected by Parkinson’s disease. This study may lead to a new treatment for Parkinson’s disease that will reduce or even reverse symptoms with improvements in the ability to walk, talk, eat, and smile, especially when combined with other medications.

Next Steps for Development:
If this study is successful, the drug will be tested in more patients and at different doses. This “efficacy testing” would determine the best dose of the drug to help people with Parkinson’s disease and whether it performs better than existing medications for Parkinson’s disease (or if a combination treatment is better).

https://www.michaeljfox.org/grant/evaluation-anavex2-73-blarcamesine-participants-parkinsons-disease



The Michael J. Fox Foundation (MJFF):

Tracking Drug that Improves Cognition: Anavex Life Sciences is testing a drug with the potential to slow or stop Parkinson’s. ANAVEX2-73 activates the sigma-1 receptor protein, which protects brain cells from harmful stress and toxic protein buildup. After ANAVEX2-73 showed improvement on thinking and memory in people with Parkinson’s disease dementia, the company is studying how the drug works in the brain through imaging scans and blood tests. This can help guide future trials. We previously funded Anavex for laboratory studies toward development of ANAVEX2-73.

https://www.michaeljfox.org/news/what-we-fund-11m-projects-investigating-new-parkinsons-treatments-and-learning-more-about

Parkinsons News Today:

Lead product candidate, AVAVEX 2-73, works by specifically targeting misfolded proteins known to play key roles in a wide range of neurodegenerative diseases, including Alzheimer’s and Parkinson’s disease. Scientists believe the drug can boost the body’s immune system through activation of sigma-1 and muscarinic receptors, which then facilitate cells’ return to a “homeostatic” state.

“The development of disease-modifying therapies for Parkinson’s disease is the top priority of The Michael J. Fox Foundation and ANAVEX 2-73 presents a promising approach,” said Marco Baptista, PhD, Senior Associate Director of MJFF Research Programs. “Companies that receive funding from MJFF have scientifically compelling plans that hold obvious potential to impact our understanding of Parkinson’s and ultimately the development of improved treatments for people with the disease. To that end, we look forward to the results of the ANAVEX 2-73 study.”

“If successful, this study will accelerate the translation of preclinical findings into the very first clinical trial of ANAVEX 2-73 as a potential disease-modifying therapy for Parkinson’s disease,” said Angela Cenci, MD, PhD, and Professor at Lund University, where the study will be conducted. “We are in the fortunate position that ANAVEX 2-73 has already been tested for safety and tolerability in humans, and was found to be a good clinical drug candidate.”

https://parkinsonsnewstoday.com/2015/08/12/anavex-receives-grant-from-michael-j-fox-foundation-for-parkinsons-research-with-anavex-2-73/

Pipeline Review:

The change in Mini Mental State Examination score (MMSE-?) (MMSE difference recorded for every single study subject at the beginning and the end of the five week period) from baseline to 5 weeks as a function of ANAVEX 2-73 dose was examined using linear regression analysis. Among 32 patients treated with doses of ANAVEX 2-73 ranging from 3mg to 50mg/day, the MMSE-? data showed a positive slope with confidence intervals not including the zero-value, consistent with a dose dependent improvement in MMSE scores over 5 weeks. The effect was unidirectional and also positive on another pharmacodynamic readout, the ERP-? P300 amplitude.

The dose-response results were robust to statistical resampling (bootstrap analysis x 10,000 resamples). Analysis of variance and post hoc tests as well as Bayesian hierarchal analysis further confirmed that the higher doses achieved a statistical significant improvement in the MMSE-? score over 5 weeks compared to the lower doses. Based on these findings, it was estimated that an oral dose of 30 mg ANAVEX 2-73 had approximately 80% probability of achieving a +2 points or higher improvement in MMSE score over 5 weeks of treatment. Doses in this range have thus far been well tolerated by the study’s subjects, with no adverse events reported above grade one.

https://pipelinereview.com/index.php/2016011160157/Small-Molecules/Anavex-Announces-Positive-Dose-Response-Data-for-ANAVEX-2-73-in-Alzheimers-Disease-Patients.html