Anavex Life Sciences Corp (AVXL)

[XenaLives]

Hampel SPEAKS!.... (update2 )

Transcript from tradeherpete for those who, like myself, have trouble understanding the accent:

The exciting part after the P2a trial and the extension trial where, I think it’s very important to know that we did whole genome sequencing of the patients who were involved in the P2a trial extension. And we found that there is a gene variant of the sigma one receptor gene. That is actually seen in 20% of patients. And these patients with this gene variant show a less favorable response than people with the Wild type. So people with the Wild type S1R gene have an improved response to the drug. That has been established as an exploratory outcome within the P2a study.

So in the upcoming large scale P2b/3 study, in 450 patients with early AD, we are planning to look at 2 aspects again, stratification regarding the genomics of the patients. We look at Wild types of the S1R gene carriers vs variant receptor carriers. And we expect a differential response depending on the genetic background. So using a genetic biomarker in studies like a one step forward to a Precision Medicine approach, in neuroscience there has already been successfully established in the field of Oncology with various drugs and cancers.

So I think this is a crucial step forward to improve the potential of a drug to get to it’s intended target and to reach the right patients at the right time. This is why we are doing it to promote also this Precision Medicine approach. This is why the Alzheimer’s Precision Medicine Initiative and Anavex are collaborating on this project.

Two additional videos with summaries from Neurology Live.
https://www.neurologylive.com/videos

Harald Hampel, MD, PhD, MA, MSc: Phase IIa Study of ANAVEX 2-73 in Treatment of Alzheimer Disease

The phase IIb/III study is scheduled to initiate enrollment of approximately 450 patients, randomized 1:1:1 to 2 different ANAVEX 2-73 doses or placebo.

Harald Hampel, MD, PhD, MA, MSc on Advancements and Challenges in the Alzheimer Space

Hampel looks to the future of the Alzheimer space and sees promise, especially since there’s transfertilization from other advanced science fields in medicine like oncology, diabetes research and rheumatology.




From MycroftHomes:

“Wild Type” which is the random population that does not have the genetic flag.

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Thanks to TTTav66 for posting the original link on Facebook and this additional information:

The Alzheimer's Precision Medicine Initiative (APMI).
Quote:
The Alzheimer’s Precision Medicine Initiative (APMI) is an international collaboration of leading interdisciplinary clinicians and scientists devoted towards the implementation of PM in Neurology, Psychiatry and Neuroscience.

You can download a paper giving an overview of their work and mission here*: https://www.researchgate.net/publication/313540863_A_Precision_Medicine_Initiative_for_Alzheimer's_disease_the_road_ahead_to_biomarker-guided_integrative_disease_modelin



And in an interesting side note, Dr. Hampel pointed out in a tweet last week that Janet Woodcock (Director of Center for Drug Evaluation and Research(CDER)) co-authored this paper with them earlier this year: https://www.sciencedirect.com/science/article/abs/pii/S1043661817313300

Janet Woodcock speaking on biomarker qualification:

From dia76ca:

Here is an outline of the study co-authored by Hampel and Woodcock et.al.

 
 1.   Introduction: precision pharmacology in the context of precision  
      medicine  
   1.1. The road to precision pharmacology: role and contribution of time  
        and space in systems biology for research & development programs  
    1.1.1. Role of time  
    1.1.2. Role of space  
 2. Homeostasis and pathway-based therapy  
 3. Current status of blood-based biomarkers – inflammatory and  
    metabolomic – for preclinical Alzheimer’s disease  
    3.1. Inflammatory biomarkers  
    3.2. Metabolomic biomarkers  
    3.3. Biomarker perspectives  
       3.3.1. Biomarkers as diagnostics  
       3.3.2. Biomarkers as guides to therapeutics  
 4. Cns inflammation in Alzheimer’s disease stages biomarkers and  
    therapeutic targets  
 5. Anti-amyloid beta and anti-tau therapeutic strategies  
 6. Rethinking and optimizing the design of clinical trials from the  
    precision medicine perspective  
    6.1. The right drug  
    6.2. The right dose  
    6.3. The right patient  
    6.4. Conduct of precision medicine trials for Alzheimer’s disease  
 7. How can drug discovery programs in Alzheimer’s disease accomplish a good level of translational quality to reduce the rate of failures?  
    7.1. Drug discovery translational for Alzheimer’s disease  
         therapeutics  
    7.2. Inadequate drug discovery process  
    7.3. Inadequate target engagement to test the therapeutic hypothesis  
    7.4. Therapeutic hypothesis is changed to accommodate the compound  
         properties  
    7.5. What can we do better?  
 8. Perspectives  
  
 Contributors to the Alzheimer precision medicine initiative – working group (APMI–WG)  
 

https://www.sciencedirect.com/science/article/abs/pii/S1043661817313300

I notice Abbvie is part of this consortium. I wonder if they might be a potential partner?

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From Doc328:

So, it looks like they will be enrolling all genetic types. Thus, about 360 patients will be S1R-WT and about 90 patients will be S1R-var. Then at study end they will analyze the data stratified by the gene.

The proposed P2/3 looks well designed (placebo controlled, randomized, standard outcomes such as ADAS-cog and CDR-SB, etc)and should be large enough to get real data. I look forward to those results. The only thing I don't like about the study is that they have MMSE 20-28 as inclusion criteria (based on HH's slide at AAIC) and many MMSE 27 and 28 (MCI not mild AD) patients would not be expected to decline over 48 weeks. This potentially weakens a treatment effect if the numbers of these patients are too high.

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Is it possible the 27-28 could be predicted to decline as early AD patients? Maybe this is also part of learning about early decline with MCI types?

IMO, its very probable that their inclusion is to get two shots on goal -- one for mild Ad and one for MCI. Many studies show that the best time to make an impact is early in the disease and with PET, some MCI patients get diagnosed with AD earlier. If both groups are successful, they can include both in their final Phase 3 and if only one is successful, they can study that one in Phase 3. If none are successful, there's always A371.


MCI, when based on cognitive screens like MMSE, converts to AD at about 20% per year so many just stay at MCI x 3-5 years. Amnestic MCI (patients lost points for the short term recall and are normal elsewhere) has higher conversion to AD than non-amnestic MCI but most are still MCI at 48 weeks. Since amyloid PET and/or CSF is a criteria for entry (based on HH's AAIC talk), then all MCI patients enrolled in the P2/3 are theoretically at higher risk of progressing to AD so rate would probably be > 20%, though I doubt > 50% in 48 weeks.

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Meanwhile, the government healthcare system of France refuses to pay for worthless Alzheimer's drugs:

"The experts of the HAS are independent". "This is a purely medical decision.These drugs were evaluated twice by the High Health Authority (including once during the period when Agnes Buzyn was the president, ed.) Twice, experts have estimated that these drugs were more harmful than beneficial to patientsand that it was no longer necessary to pay them back, "she explained.This measure concerns four drugs (Aricept, Ebixa, Exelon, Reminyl) and their generics.As soon as it was announced on Monday, it sparked protests from the France Alzheimer Association, as well as learned societies of neurology and geriatrics. "The experts of the High Health Authority are independent, and they consider that these drugs are toxic. I am followed by a large number of associations of health professionals, including generalists, "insists Agnès Buzyn.

....

"Not a financial subject". But faced with the anxiety of patients and their families, the minister tries to reassure. "I am a scientific opinion, but I do not want people to think that it is a financial subject, all the money saved will be redirected towards supporting people with Alzheimer's disease, for memory centers, either for the medico-social sector that supports them.There will be no savings made on the back of patients, "she certified. In France, 850,000 to 900,000 people would be affected by Alzheimer's and related diseases.

Video and link:
http://www.europe1.fr/politique/deremboursement-des-medicaments-anti-alzheimer-une-decision-purement-medicale-insiste-agnes-buzyn-3668855


*Note that in the above linked research paper Dr. Hampel is affilited with the Sorbonne in France. I don't think this is coincidence.


Additional discussion of cholinesterase inhibitors from Hampel:
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=142852143

Canadian position on cholinesterase inhibitors:
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=142852221

Canada and Australia are deprescribing cholinesterase inhibitors.
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=142856007