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I too will continue to hold and to accumulate more shares outright or by employing option stratgies. Of course, this is not a recommendation for anyone. It is simply a statement of my preference to maintain and increase my investment in shares of Anavex based on my research/DD.
Bio: This is priceless. Thank you.
Dado: Thank you for this excellent post!
TTT: Superb research! Thank you.
Steady_T: Thank you. It is a huge step assuming confirmation in the new trial. Hopefully, other advances will soon follow whether by Anavex or others. My thinking is that this one step will change the direction of the approach to treat AD and other CNS diseases. Change is needed and once it becomes obvious many others will follow in this different direction instead of repeated attempts at what has failed.
Good thinking Power. I say this based on my thoughts about Talon’s post a moment ago. https://investorshub.advfn.com/boards/m_read_msg.aspx?message_id=143736382
Talon:
Very good, thank you. The timing and location of the trials are ideal. Moreover, the circumstances involving Biogen and Anavex support what you say about Anavex being Biogen’s hope, most likely, or worst nightmare, not likely because they will do some sort of a deal if Anavex continues to demonstrate what Ariana says it has helped Anavex to do. Ariana Pharma helps ANAVEX® demonstrate efficacy of its Alzheimer’s therapy in phase IIa clinical trial. http://www.arianapharma.com/2018/09/alzheimer-precision-medicine/
Biogen/Anavex. Is all of the following related?
On September 28, 2016, Anavex announced an agreement with Biogen to test AVZL 2-73 to see if it permits or promotes remyelination. See #1 below.
A year later, on October 27, 2017, Anavex announces that AVXL 2-73 might promote remyelination based on new data related to MS. See #2. Do you or does anyone know anything about this "new data" Anavex refers to in October 2017?
The new data was presented in Paris. Hall B, Le Palais des Congrès de Paris, 2 Place de la Porte Maillot, 75017 Paris, France. #2 below.
On October 27, 2017, Biogen tweets this: Remyelination may lead to improvements in neurologic function in people #LivingwithMS #MSParis2017. #3 There is no mention of Anavex, and I cannot find where Biogen has mentioned anything about Anavex or its agreement with Anavex between September 2016 to date. It seems, however, that this Biogen tweet came from the same conference wherein the new data was presented regarding AVXL and MS. #2 below.
1. Anavex announces the agreement with Biogen to test AVXL 2-73 relative to permitting remyelination. September 28, 2016
https://www.anavex.com/anavex-compound-to-be-tested-in-biogen-neurological-protection-model/
“Battling demyelinating diseases such as multiple sclerosis requires an understanding of the processes that cause remyelination to fail. Remyelination of demyelinated axons is typically a function of oligodendrocyte precursor cells. These studies will examine the therapeutic role ANAVEX 2-73 may play in permitting remyelination in the brain,” said Christopher U. Missling, PhD, President and Chief Executive Officer of Anavex.
2. ANAVEX®2-73 Shown to Protect and Repair Myelin Forming Cell. October 27, 2017.
https://www.anavex.com/new-data-related-to-multiple-sclerosis/
Note: New data presented at Hall B, Le Palais des Congrès de Paris, 2 Place de la Porte Maillot, 75017 Paris, France
See: http://www.acnr.co.uk/2017/10/ms-paris-2017-the-joint-ectrimsactrims-meeting-a-conference-review/
'''A unique feature of ANAVEX®2-73, compared to another sigma-1 receptor agonist we studied, is that ANAVEX®2-73 accelerates the maturation of oligodendrocyte precursor cells (OPC) to oligodendrocytes (OL)” said Dr Robert P. Lisak. “This is an important feature since OPCs can replace lost OLs by maturing into new potential myelin-producing cells. In other words, ANAVEX®2-73 might promote remyelination. Further data also demonstrates that ANAVEX®2-73 provides protection for OL, OPC’s, as well as central nervous system neurons in addition to helping repair by increasing OPC proliferation and maturation in tissue culture.“'
3. October 27, 2017 Biogen tweets this: Remyelination may lead to improvements in neurologic function in people #LivingwithMS #MSParis2017
Remyelination may lead to improvements in neurologic function in people #LivingwithMS #MSParis2017 pic.twitter.com/dQddrJ61GB
— Biogen MS (@biogenms) October 27, 2017
TTT: Thank you. Ariana is coming right out with and stating ”efficacy”, ”actionable genetic variant biomakrers”, identification of patients that benefit from AVXL 2-73 and go on to say ”a confirmed response with ANAVEX 2-73”. These are strong and confident words.
”Ariana Pharma helps ANAVEX® demonstrate efficacy of its Alzheimer’s therapy in phase IIa clinical trial.
Ariana’s KEM® Artificial Intelligence technology has resulted in the identification of the first actionable genetic variant biomarkers, selecting a specified Alzheimer’s disease population, who demonstrated a confirmed response with ANAVEX®2-73.”
Yes! ”All things are poison.” Every prescription drug is toxic. Prescription drugs are especially toxic. Prescription drugs have to be potent to obtain a response in the body. It is all about the dosage. Thus, the saying: ”The dose makes the poison.”
”All things are poison, and nothing is without poison, the dosage alone makes it so a thing is not a poison.
—Paracelsus[1]
"The dose makes the poison" (Latin: sola dosis facit venenum) is an adage intended to indicate a basic principle of toxicology. It is credited to Paracelsus who expressed the classic toxicology maxim "All things are poison, and nothing is without poison, the dosage alone makes it so a thing is not a poison." This is often condensed to: "The dose makes the poison" or in Latin, "Sola dosis facit venenum". It means that a substance can produce the harmful effect associated with its toxic properties only if it reaches a susceptible biological system within the body in a high enough concentration (i.e., dose).[2]”
https://en.m.wikipedia.org/wiki/The_dose_makes_the_poison
Bio’s post is correct.
Professor Harald Hampel, MD, PhD, AXA Research Fund & Sorbonne University Excellence Chair, Department of Neurology, Sorbonne University, Paris. Speaker of the Alzheimer Precision Medicine Initiative (APMI)
"It is time for a paradigm shift towards the implementation of precision medicine using supportive pathophysiological biological markers for enhanced risk screening, detection, patient recruitment and treatment of Alzheimer's disease". "The biomarker-guided ETHERAL trial is bringing us one step closer to realizing the potential of a precision medicine and precision pharmacology approach to treating this devastating disease."
It is time for a paradigm shift - especially in the area where drugs developed under the old system for serious diseases like AD do not work. However, people are uncomfortable with anything that is new and they are resistant to change.Most people do not like change of any sort.
Bob Farrell said something that not only applies to the stock market generally to everything that goes on in life. The stock market reflects sentiments of how particpates, people, react. As Bob Farrell observed:
“Change of a long term or secular nature is usually gradual enough that it is obscured by the noise caused by short-term volatility. By the time secular trends are even acknowledged by the majority, they are generally obvious and mature. In the early stages of a new secular paradigm, therefore, most are conditioned to hear only the short-term noise they have been conditioned to respond to by the prior existing secular condition. Moreover, in a shift of secular or long term significance, the markets will be adapting to a new set of rules while most market participants will be still playing by the old rules.”
For the most part, scientists and members of the medical profession deal with what they believe is the ”known”. Anavex has moved forward into ”unknown” territory, and all of these people that are comfortable with the ”known” desire to stay where they are in that comfort zone. They are conditioned to hear only the noise they have been conditioned to by the existing secular condition. This has been true throughout history. Recall, the beliefs such as the earth is flat, the sun revolves around the earth, Semmelweis proposed practice of washing hands with chlorinated lime solutions in 1847 while working in a Vienna hospital, and many other examples met with resistance throughout history.
We will continue to hear voices of resistance, but I am convinced by years of research by members of this board that we are on the right path.
So yes, even scientists may be resistant to change, and then there is this thing about ”influence” as an article in today’s WSJ suggests.
Drugmakers’ Free Services Spur Government Scrutiny -WSJ today - Biogen in the news.
”Federal prosecutors are probing whether big drug makers including Sanofi SA, Gilead Sciences Inc. and Biogen Inc. potentially violated laws by providing free services to doctors and patients, according to a Wall Street Journal review of securities filings.
Drug companies say the services, such as nurses and reimbursement assistance, help doctors and patients. But the practices, which have become more prevalent as drugmakers have intro-duced more complex and expensive drugs, are drawing scrutiny over whether they serve an illegal commercial purpose: inducing sales.”
With the amount of money at stake, there will always be ways invented to ”influence”.
279 Assessment of various biomarkers may provide supportive evidence for a drug that has an
280 established clinically meaningful benefit, but the effects on biomarkers in AD are not sufficiently
281 well understood to provide evidence of a persistent effect on disease course.
282
283 Currently, there is no consensus as to particular biomarkers that would be appropriate to support
284 clinical findings in trials in early AD. For this reason, sponsors at present have insufficient
285 information on which to base a hierarchical structuring of a series of biomarkers as secondary
286 outcome measures in their trial designs. Sponsors are therefore encouraged to analyze the results
287 of these biomarkers independently, though in a prespecified fashion, with the understanding that
288 these findings will be interpreted in the context of the state of the scientific evidence at the time
289 of a future marketing application.
Early Alzheimer’s Disease: Developing Drugs for Treatment Guidance for Industry
https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM596728.pdf
Bio and Kevli:
Excellent detective work. This is reassuring. We should all be thankful we have the addition of Dr. Goodsaid.
”Confirms role of patient selection biomarkers” I think that is significant going forward with our trials with all trials using these same biomarkers.
http://www.ctad-alzheimer.com/files/files/Late%20call%20for%20abstracts.docx.pdf
Thank you. And in Barcelona of all places.
Neiu: Thank you. Note that this patent pertains to:
”This invention addresses tetrahydro-N,N-dimethyl-2,2-diphenyl-3-furanmethanamine hydrochloride (ANAVEX2-73, AV2-73, or A2-73), ANAVEX1-41 and/or Anavex19-144 in a method of treatment for neurodevelopmental disorders. Particular reference is made to the treatment of autism spectrum disorder, cerebral palsy, Rett syndrome, Angelman syndrome, Williams syndrome, pervasive developmental disorder not otherwise specified (PDD-NOS), childhood disintegrative disorder, and Smith-Magenis syndrome. Additional reference is made to multiple sclerosis.”
What about the additional reference to MS?
Bio’s and Xena’s case for accelerated approval of AVXL 2-73 is compelling. I offer this in addition.
The Anavex clinical trial in Spain targets an unmet need in the treatment of PDD. If AVXL 2-73 demonstrates safety and any degree of efficacy, the approval of this drug will be accelerated in Spain and the EU. Australia, although not a member of the EU, is closely aligned with the EU in regulation of prescription drugs. If the shorter PDD trial in Spain is successful, I believe this will be a reason to support accelerated approval of AVXL 2-73 for PDD in Spain and the EU and for accelerated approval of AVXL 2-73 for AD in Australia and eventually the EU.
Accelerated approval in the EU
https://www.clinicaltherapeutics.com/article/S0149-2918(16)30455-6/fulltext
Accelerated Approval Paths: What they do Mean and What they Should Not Mean?
G. Calvo
Hospital Clinic of Barcelona and University of Barcelona School of Medicine, Barcelona, Spain
PlumX Metrics
https://doi.org/10.1016/j.clinthera.2016.07.012
Cognitive impairment in Parkinson’s disease: a report from a multidisciplinary symposium on unmet needs and future directions to maintain cognitive health
https://www.nature.com/articles/s41531-018-0055-3
Therapeutic Goods Administration in Australia is closely aligned with European Guidelines.
”EU guidelines
The TGA closely aligns its regulatory approaches to therapeutic products with those of comparable international regulatory counterparts wherever possible.
Technical data requirements for applications to register or vary the registration of prescription medicines in Australia are closely aligned with requirements set out in relevant European Union (EU) Guidelines and Guidelines issued by the International Conference on Harmonisation (ICH) of Technical Requirements for Registration of Pharmaceuticals for Human Use.
Prior to adopting an EU or ICH Guideline, the TGA undertakes an extensive process of internal and external consultation to ensure the Guideline is consistent with prevailing requirements in Australia. TGA publishes a List of European Union and ICH Guidelines adopted in Australia.
The Australian legislative requirements applying to prescription medicines are contained in the Therapeutic Goods Act 1989 and the Therapeutic Goods Regulations 1990, as well as in various legislative instruments such as Therapeutic Goods Orders, Notices and Determinations, see Legislation & legislative instruments.
While EU and ICH technical Guidelines adopted in Australia are generally not mandated in Australian legislation they provide guidance to sponsors to assist them to meet the legislative requirements and any deviation from a Guideline relevant to an application to register or vary the registration of a medicine must be justified.
Please Note: Where EU guidelines adopted in Australia include references to EU legislation (including EC Directives and Regulations), the requirements contained in the referenced EU legislation are not applicable to the evaluation of prescription medicines by the TGA.”
https://www.tga.gov.au/publication/scientific-guidelines
As I posted once before:
Australia and Spain - Excellent Choices for Anavex Trials.
Spain encourages clinical trials to be conducted in country, and Spain passed new regulations on clinical trials to increase transparency and simplify procedures. See: http://www.barcelonaclinicaltrials.org/en/spain-passes-new-regulations-clinical-trials-increase-transparency-and-simplify-procedures.
It seems that recruitment of patients for clinical trials in Spain with its National Healthcare system is likely to move along more quickly than in many other countries. http://www.farmaindustria.es/web_en/documents/press-releases/2017/03/09/clinical-trials-early-stages-growing-steadily-spain-already-make-51-total/
We do know that recruitment for the PDD trial in Spain commenced. http://pddtrial.com
The Spanish healthcare system is one of the best in the world.
https://www.expatica.com/new/es/healthcare/general-healthcare/healthcare-system-101467/
Life expectancy in Spain ranks number 3 in the world
http://www.worldlifeexpectancy.com/spain-life-expectancy
Spanish have highest healthy life expectancy in Europe
https://www.theguardian.com/world/2013/mar/05/spanish-highest-life-expectancy-europe
Australia is an ideal country for Alzheimer’s clinical trials because it offers more support for the trials, including funds for our trials.
It has also launched the world-first dementia network to fast-track treatment and research.
https://www.9news.com.au/national/2018/07/02/20/06/australian-dementia-network-launched-to-track-diagnosis-and-care-of-patients
As far as locations for Anavex trials are concerned we are good to go. I am thankful Anavex chose to conduct two of its clinical trials in Australia and Spain, and I say this after much research and thought.
Thank you. Interesting, after you retrieve the first page of this website, click on ES (trial protocol) for details. Go to estimated duration of the trial. It says 5 months.
http://www.clinicaltrialsregister.eu/ctr-search/trial/2017-004335-36/ES
Additionally, the other web site you provided, in addition to the one above, now shows 7 hopsital sites active versus 6 shown active last week.
Glucose Metabolism - M3 and SR1 activation may restore blood pressure to normal levels as I posted yesterday. Abnormal blood pressure resulting in impaired cerebral blood flow is associated with AD. M3 also plays a role in glucose metabolism. Impaired glucose metabolism is a dementia/AD risk.
New findings on glucose metabolism, oxidative stress and Alzheimer’s disease
May 22, 2017
“Glucose metabolism, oxidative stress and AD
Impairment in glucose metabolism and insulin resistance has been a hot topic in AD research in recent years, and for good reason. Type II diabetes is a known risk factor for AD – in a recent review, Saedi and colleagues noted a 45–90% association of diabetes with AD, and also that even pre-diabetes, regardless of progression, confers a higher risk of AD. Brain atrophy has also been noted in diabetic patients (3).
The link between Type II diabetes and AD may lie in the effects of glucose metabolism dysregulation and oxidative stress. Verdile et al. note that 3 aspects of insulin resistance present in Type II diabetes, hyperglycemia, hyperlipidemia and hyperinsulinemia, are all known to boost accumulation of amyloid beta, one of the hallmarks of Alzheimer’s disease, and that the inverse, amyloid beta promoting insulin resistance, has also been demonstrated in the liver. Even independent of insulin resistance, studies have shown that excess glucose leads to persistently higher amyloid beta in interstitial fluid as well as lowered neuronal activity and hippocampal metabolism, suggesting that these damaging processes may begin even prior to full-blown T2D (4).”
http://biomarkerinsights.qiagen.com/2017/05/22/ngs-glucose-metabolism-and-alzheimers/
Role of the M3 muscarinic acetylcholine receptor in ß-cell function and glucose homeostasis
Abstract
The release of insufficient amounts of insulin in the presence of elevated blood glucose levels is one of the key features of type 2 diabetes. Various lines of evidence indicate that acetylcholine (ACh), the major neurotransmitter of the parasympathetic nervous system, can enhance glucose-stimulated insulin secretion from pancreatic ß-cells. Studies with isolated islets prepared from whole body M3 muscarinic ACh receptor knockout mice showed that cholinergic amplification of glucose-dependent insulin secretion is exclusively mediated by the M3 muscarinic receptor subtype. To investigate the physiological relevance of this muscarinic pathway, we used Cre/loxP technology to generate mutant mice that lack M3 receptors only in pancreatic ß-cells. These mutant mice displayed impaired glucose tolerance and significantly reduced insulin secretion. In contrast, transgenic mice overexpressing M3 receptors in pancreatic ß-cells showed a pronounced increase in glucose tolerance and insulin secretion and were resistant to diet-induced glucose intolerance and hyperglycaemia. These findings indicate that ß-cell M3 muscarinic receptors are essential for maintaining proper insulin secretion and glucose homeostasis. Moreover, our data suggest that enhancing signalling through ß-cell M3 muscarinic receptors may represent a new avenue in the treatment of glucose intolerance and type 2 diabetes.
https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1463-1326.2007.00781.x
Yes, I agree.
AVXL 2-73 may be eligible for accelerated approval for treatment of PDD, an unmet need.
Accelerated approval in the EU
https://www.clinicaltherapeutics.com/article/S0149-2918(16)30455-6/fulltext
Accelerated Approval Paths: What they do Mean and What they Should Not Mean?
G. Calvo
Hospital Clinic of Barcelona and University of Barcelona School of Medicine, Barcelona, Spain
PlumX Metrics
https://doi.org/10.1016/j.clinthera.2016.07.012
Cognitive impairment in Parkinson’s disease: a report from a multidisciplinary symposium on unmet needs and future directions to maintain cognitive health
https://www.nature.com/articles/s41531-018-0055-3
Sorry, l was tired last night. I misunderstood your post.
I think Investors reply to your post is a good guess. I add the following:
In Parkinson disease dementia, postural instability and gait abnormalities are more common, motor decline is more rapid, and falls are more frequent than in Parkinson disease without dementia. https://www.merckmanuals.com/professional/neurologic-disorders/delirium-and-dementia/lewy-body-dementia-and-parkinson-disease-dementia
Our PDD trial ”...will focus on the effect of ANAVEX®2-73 on both the cognitive and motor impairment of Parkinson’s disease,” said Christopher U Missling, PhD, President and Chief Executive Officer of Anavex. “We continue leveraging our precision medicine approach to drug development to provide intelligence beyond many traditional neurology trials to disease areas with high unmet needs.”’
”The brain changes caused by Parkinson’s disease begin in a region that plays a key role in movement. As Parkinson’s brain changes gradually spread, they often begin to affect mental functions, including memory and the ability to pay attention, make sound judgments and plan the steps needed to complete a task.[1]”
[1] Source: www.alz.org/dementia/parkinsons-disease-symptoms
https://www.anavex.com/anavex-life-sciences-receives-approval-to-initiate-phase-2-clinical-trial-of-anavex2-73-for-the-treatment-of-parkinsons-disease-dementia/
I suppose that if our drug is works in the PDD trial an improvement in noticeable/measurable movement and functions will be detectable in a shorter time frame. If improvement occurs with the 80% genetic group versus the 20% genetic group and/or the placebo group, it will be presumed that our drug is causing this meaningful result -- just my guess.
Power:
Bio posted detailed discussions about this today that you should read. Briefly, it is believed, from the genome work do so far, that AVXL 2-73 may get the same response from patients in the PDD trial as we have seen so far in the AD trial.
All three clinical trials (AD, PDD and Rett) will be looking at the same genetic groups as identified in the AD Phase 2a trial. If we can show that patients included in the 80% genetic success group show positive results for AVXL 2-73 whereas the 20% genetic group does not respond to the drug, we can attribute the drug’s success to the gene matching identified in Anavex’s genome work completed and announced at AIC 2018.
In other words, it is expected that our drug, if successful, should get a positive response from the 80% of patients that have genes matching the 80% of the patient population and those that do not get the same result, 20% of the population, should be in the genetically identified failure group. if we get the same response in the PDD trial as has been identified in the AD trial this far, it should indicate proof of efficacy to be further confirmed later with the completion of the AD Phase 2/3 trial (48 months), which will be longer than the PDD trial in Spain (14 months).
It is getting late for me so I hope I have accurately expressed what we will be looking for in any or all of the 3 clinical trials. We can discuss this more later.
Anavex should not fire Missling. Anavex is attempting something transformational, which takes time. I say this from personal and other experiences.
I have a personal understanding of cancer immunotherapy. It is limited to me. I will get back to this later, and why it is relevant to understanding what Anavex and Missling are doing. First, here is a little background.
I have 20 years experience with problems and delays involved in clinical trials, drug development, regulatory approvals, and more, which I will not delve into entirely in this short post. Instead, I will provide a more personal point of view. I suppose my experiences in life relevant to the current tipoc, although I did not know it at the time begin long ago. Before Vietnam in the 1960s where I served as a young Marine, but I will begin there. I was lucky. My first cousin and best friend were not. My best friend died instantly. My first cousin is living a mentally tormented life with intervals of relief as long as he receives his monthly VA ”shot.”
I believe that I am the luckiest person in life that I know. I had thought this from childhood when my sister was stricken with a dilabiating CNS disease carried by a mosquito, and I continue with this belief to this very day based on problems experienced by relatives and friends my age and older.
My encounter with immunotherapy grew out of cancer I developed presumed to be related to agent orange exposure in Vietnam. I was determined to overcome that problem. I did research, and I found a small gene therapy trial in progress in Houston at Methodist Hospital conducted by Dr. Butler and Dr. Teh. It was labeled a suicide gene therapy trial. This clinical trial was in the 1990s. I will spare you the details, but I had a severe immune response, and my wife thought I was dying. Unfortunately, this small trial was shut down for several reasons that have nothing to do with the effectiveness of the excellent people conducting it. I believe that clinical trial is at least partially responsible for me being here today. I prefer to believe it altered my immune system to recognize and destroy cancer.
I continue to visit with Dr. Butler and Dr. Teh every year. They remain dedicated to finding treatments for cancer, and they together with others have made progress. However, it has taken a very long time because of a multitude of reasons whether environmental with flooding in Houston where their lab was in a basement, political and religious beliefs, regulatory barriers, competition, etc.
My point in telling you all this is to attempt to relate to you that developing a new and transformational drug -- especially one that may do something that no one has ever accomplished -- takes a very long time regardless of the highly competent and skilled people that are striving to do so.
I hope you can begin to understand that what Anavex is attempting to do. It is a far cry from executing a turn around in existing technology company producing chips and other components not subject to the barriers and problems involved with drugs digested or injected into human beings. My journey in life is a long one. Based on that journey, I do not understand this idea about merely hiring new management in this particular area of finding a new treatment for human beings that will execute, execute, execute to suit our impatience and short-term desires. It is not possible given the environment for startup biotech clinical trial development, and I do not know of any good reason to fire Christopher Missling to suit the whims of shareholders.
Progress in drug development has always been slow. However, I have a purpose in living, and I hope I live long enough to see more growth in drug development, especially in the CNS area.
Another reason why AVXL 2-73 may be efficacious.
Impaired cerebral blood flow is associated with dementia and Alzheimer's. AVXL 2-73 may alleviate blood pressure and increase cerebral blood flow.
Aggressive lowering of blood pressure reduces MCI risk, study shows
Jul 25 2018
Significant reductions in the risk of mild cognitive impairment (MCI), and the combination of MCI and dementia, have been shown for the first time through aggressive lowering of systolic blood pressure in new research results from the federally-funded SPRINT MIND Study reported at the Alzheimer's Association International Conference (AAIC) 2018 in Chicago.
https://www.news-medical.net/news/20180725/Aggressive-lowering-of-blood-pressure-reduces-MCI-risk-study-shows.aspx
Anavex Life Sciences Reports Potential Normalization of Hypertension with ANAVEX®2-73 Published in The Journal of Clinical Hypertension. https://www.anavex.com/anavex-life-sciences-reports-potential-normalization-of-hypertension-with-anavex2-73-published-in-the-journal-of-clinical-hypertension/
“NEW YORK, Jan. 16, 2018 (GLOBE NEWSWIRE) -- Anavex Life Sciences Corp. (“Anavex” or the “Company”) (Nasdaq:AVXL), a clinical-stage biopharmaceutical company developing differentiated therapeutics for the treatment of neurodegenerative and neurodevelopmental diseases today reports that the peer-reviewed scientific journal The Journal of Clinical Hypertension [1] has published a post-hoc analysis of blood pressure data collected during the Phase 2a study in mild-to-moderate Alzheimer’s disease patients demonstrating that ANAVEX®2-73 seems to normalize systolic blood pressure (SBP) in a patient population with risk for hypertension.
… High blood pressure, or hypertension, occurs when either systolic or diastolic pressure remains elevated over time. High blood pressure is dangerous because it makes the heart work too hard and its extra force can damage arteries. Uncontrolled high blood pressure can lead to heart disease, kidney damage or stroke. New evidence also links high blood pressure to increased risk of cognitive decline and dementia. [2] https://www.alz.org/we_can_help_blood_pressure.asp
… Blood pressure measurement was not a primary goal of this trial, however, the potential beneficial effect of sigma-1 receptor activation restoring homeostasis on blood pressure normalization merits further investigation in future clinical studies,” stated Christopher U. Missling, PhD, President and Chief Executive Officer of Anavex.”
It is interesting to note that the majority of the patients in the Anavex Phase 2a study had elevated blood pressure according to Missling.
See also:
Systolic blood pressure as a potential target of sigma-1 receptor agonist therapy
https://onlinelibrary.wiley.com/doi/full/10.1111/jch.13197
“.. Based on existing physiologic evidence, this class of medication might have a feasible mechanism for BP reduction. In rats, sigma-1 receptor stimulation promotes endothelial and neuronal nitric oxide synthase activation and nitric oxide production, resulting in vasodilation and potentially mediating BP decline.3 In addition to acting as a sigma-1 receptor agonist, ANAVEX2-73 also has muscarinic (M1–M4) receptor activity. M3 receptor stimulation triggers nitric oxide–mediated central vasodilation.7Medication-induced activation of this receptor may further contribute to BP reduction.“
Vasodilation is the widening of blood vessels.[1] It results from relaxation of smooth muscle cells within the vessel walls, in particular in the large veins (called venodilators), large arteries, and smaller arterioles. The process is the opposite of vasoconstriction, which is the narrowing of blood vessels.
https://en.m.wikipedia.org/wiki/Vasodilation
”When blood vessels dilate, the flow of blood is increased due to a decrease in vascular resistance. Therefore, dilation of arterial blood vessels (mainly the arterioles) decreases blood pressure. The response may be intrinsic (due to local processes in the surrounding tissue) or extrinsic (due to hormones or the nervous system). In addition, the response may be localized to a specific organ (depending on the metabolic needs of a particular tissue, as during strenuous exercise), or it may be systemic (seen throughout the entire systemic circulation).
Endogenous substances and drugs that cause vasodilation are termed vasodilators. Such vasoactivity is necessary for homeostasis (keeping the body running normally).”
https://www.health.harvard.edu/newsletter_article/blood-pressure-and-your-brain
Blood pressure and your brain
Published: October, 2009
”Hypertension is a circulatory disease. Many patients with high blood pressure develop coronary artery disease or heart failure, and many die as a result. But all parts of the body depend on the circulation, and many organs suffer from the impact of untreated hypertension. One of the organs at greatest risk is the brain.”
https://www.health.harvard.edu/newsletter_article/blood-pressure-and-your-brain
Lower cerebral blood flow in subjects with Alzheimer's dementia, mild cognitive impairment, and subjective cognitive decline using two-dimensional phase-contrast magnetic resonance imaging
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5717294/
Bio,
Your post is perfect! If we receive reports form any of the three clinical trials that indicate the link below (quote from your post) is being established in any of those trials, Anavex will attract immense interest.
"Editorial:
Once they establish the link between a response in those patients with the gene variants and none in those without, they have legitimized those as biomarkers (like a cholesterol test), as Missling states: it is necessary to have the variants and non variants in the trial in order to use the non variant as a control (that, indeed, the drug does not work) so that the biomarkers can be recognized and proven as biomarkers."
Everyone will be monitoring the Parkinson's Dementia trial in Spain for signs of whether Anavex is getting the hoped for response. Interim trial reports that give any indication that this link is again being established will create much excitement. So far, the PDD trial is the shorter of the two announced trials. I believe it is likely we may know something from that trial as opposed to the AD phase 2/3 trial, but we may receive news from Australia as well.
I would mention Rett except trial approval has not been announced, and comment abou it may invite contentious and unproductive discussions. However, I certainly do not rule it out.
Thank you for enlightening this board.
Wait, wait! The PDD trial in Spain is a dementia trial! What happens if we get good or bad results from the PDD trial? If we assume that what Clint reportedly said is true, we may be getting news of results by February - April 2019 if not before because we should receive news as the PDD trial progresses. If we receive negative dementia results in the PDD trial, we do not need to guess what may happen. However, if we receive positive news from the PDD trial, we should be attracting partners for Alzheimer’s and Parkinson's.
Therefore, 9 months (or 12 months) for the PDD trial in spain is excellent news for me. We have know all along the Phase 2/3 AD trial will be longer. The PDD trial in Spain is key.
My thinking here is, considering what we know about the scientific basis for AVXL 2-73, that if the PDD trial shows results similar to what occurred initially with the 2-73 Alzheimer’s to date we should generate serious interest.
However, Bio is better suited than to speak/elaborate about all of this.
Xena:
For the PDD trial in Spain:
Go to this site: https://reec.aemps.es/reec/public/web.html
Type in Anavex
Click on calendar symbol. Look at time line. See INICIO DE ENSAYO.
Translation: Start of the essay or study. It gives the date of 9/9/2018
However, I could not find any information to very numbers of patients enrolled.
Doc:
Go to this site: https://reec.aemps.es/reec/public/web.html
Type in Anavex
Click on calendar symbol. Look at time line. See INICIO DE ENSAYO.
Translation: Start of the essay or study. It gives the date of 9/9/2018
Bio,
I could not access the board as well, and I thought my post did not go out last night. Thank you for your reply. Based on our well documented understanding of how our drug works in restoring homeostasis within the body to allow the body to heal itself, it seems that applying our drug to cells in a Petri dish is an improbable way to ”...examine the therapeutic role ANAVEX 2-73 may play in permitting remyelination in the brain..” as Missling stated in the announcement of the Biogen agreement. https://www.anavex.com/anavex-compound-to-be-tested-in-biogen-neurological-protection-model/
So, as you suggest, maybe someone here with the appropriate background and experience can offer an explanation of what Biogen and Anavex think could be accomplished by making that agreement.
Bio:
Thank you. You are making it easier for us to read the tea leaves. Biogen is indeed interested in Anavex’s areas of focus. I think you are on to something.
After reading your post, I went back to look at the announcement of that agreement Anavex signed with Biogen in 2016. It was a material transfer agreement with Biogen in September 2016 to conduct tests with AVXL 2-73 in relation to demyelinating diseases. The studies were to ”...examine the therapeutic role ANAVEX 2-73 may play in permitting remyelination in the brain..” https://www.anavex.com/anavex-compound-to-be-tested-in-biogen-neurological-protection-model/
How does one study the role our drug plays ”in permitting remyelination in the brain” without performing work that may relate to other CNS diseases? The answer is that this study cannot be conducted without knowledge and understanding of how AVXL 2-73 effects the Central nervous system. Therefore, the study must relate to the role AVXL 2-73 plays in treating CNS diseases in general. See this previous post: https://investorshub.advfn.com/boards/read_msg.aspx?message_id=143320176
Thus, Biogen undoubtedly has and is studying AVXL 2-73 and how it may treat any CNS disease.
Bio:
Thank you. You are making it easier for us to read the tea leaves. Biogen is indeed interested in Anavex’s areas of focus. I think you are on to something.
After reading your post, I went back to look at the announcement of that agreement Anavex signed with Biogen in 2016. It was a material transfer agreement with Biogen in September 2016 to conduct tests with AVXL 2-73 in relation to demyelinating diseases. The studies were to ”...examine the therapeutic role ANAVEX 2-73 may play in permitting remyelination in the brain..” https://www.anavex.com/anavex-compound-to-be-tested-in-biogen-neurological-protection-model/
How does one study the role our drug plays ”in permitting remyelination in the brain” without performing work that may relate to other CNS diseases? The answer is that this study cannot be conducted without knowledge and understanding of how AVXL 2-73 effects the Central nervous system. Therefore, the study must relate to the role AVXL 2-73 plays in treating CNS diseases in general. See this previous post: https://investorshub.advfn.com/boards/read_msg.aspx?message_id=143320176
Thus, Biogen undoubtedly has and is studying AVXL 2-73 and how it may treat any CNS disease.
Australia’s initiative is to cut recruitment time for AD trials.
ADNet head discusses vision for future of dementia
https://www.australianageingagenda.com.au/2018/07/10/head-of-dementia-initiative-talks-to-ccr/
A new dementia initiative aims to cut recruitment time for trials from the current waiting period of three years to just six months, the man at its helm says.
“We really want to try and get a treatment, that’s what we’re crying out for,” Professor Rowe said.
“We aim reduce to recruitment time from the current three years for an average Alzheimer’s trial down to six months, and find out whether treatments are working or not much quicker.”
A new dementia initiative aims to cut recruitment time for trials from the current waiting period of three years to just six months, the man at its helm says.
Measuring effectiveness of AVXL 2-73, see:
Early Alzheimer’s Disease: Developing Drugs for Treatment Guidance for Industry
https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM596728.pdf
This is interesting. How has Anavex designed the phase 2/3 AD trial in Australia? If designed this way, this may be a measure (or an acceptable substitute for a measure) of effectiveness of AVXL 2-73, assuming these new guidelines (or at least the below alone) are/is adopted by the FDA.
”A randomized-start or randomized-withdrawal trial design (with clinical outcome measures) is the most convincing approach to demonstrating a persistent effect on disease course. Generally, a randomized-start design would be most appropriate for use in AD. In this study design, patients are randomized to drug and placebo, and at some point, placebo patients are crossed over to active treatment. If patients in the trial who were initially on placebo and then assigned to active treatment fail to catch up (after a reasonable period of time) to patients who received active treatment for the entire duration of the trial, a persistent treatment effect on disease course would have been shown.”
To find the above quote, go the the website reference and begin reading on line 270. The lines are numbered.
Yes, thank you both, Bio and Nidan, for your efforts and insight. You have provided a big leap in knowledge and understanding of the difficulties that must be overcome to make the leap to finding an effective treatment for AD that regulatory authorities will approve.
As I believe you point out, it may be that adequate or acceptable measures may be more evident with Parkinson's and some other CNS diseases. If so, our PDD trial may help to demonstrate this relatively soon. The PDD trial is shorter, and it includes fewer trial participants.
We should also look more closely how, if ever, AVXL 2-73 may be approved in Australia and what that may mean.
You have provided much food for thought. I, for one, will undoubtedly be thinking about this.
Doc:
Thank you. The Canadian company I mentioned in an earlier post, if true that Missling is a reference for that company, may be a reliable manufacturer for quality product. This is the company:
Toronto Research Chemicals, which purpotedly manufactures AVXL 2-73 for research. See the website and Missling is listed as a reference. This company's website is:
https://www.trc-canada.com/product-detail/?
CatNum=A637195&CAS=195615-84-0&Chemical_Name=Anavex%202-73&Mol_Formula=C%E2%82%81%E2%82%89H%E2%82%82%E2%82%83NO%E2%80%A2%20(HCl)#
Of course, quality and purity may not be assured. I suppose regulatory athourities have approved whatever source Anavex uses to produce AVXL 2-73 for its chemical trials, but, like you, I would be extremely cautious about ordering AVXL 2-73 from just any source. Actually, I would not try to obtain the drug unless it was done through Anavex under a right to try request or something like that. However, I am sure it would be expensive because no company is producing the drug in commercial quantities. Once approved, the regulatory authorities must approve the manufacturing facility for production of the drug as approved.
I think it can only be sold for research and certification/documentation may be required. Patent rights would prevent it from being sold without Anavex’s approval, I believe.
That was a nice buy at $2.73 today - 30,000 plus shares.
Toronto Research Chemicals manufactures AVXL 2-73 for research. See the website and Missling as a reference.
https://www.trc-canada.com/product-detail/?CatNum=A637195&CAS=195615-84-0&Chemical_Name=Anavex%202-73&Mol_Formula=C%E2%82%81%E2%82%89H%E2%82%82%E2%82%83NO%E2%80%A2%20(HCl)#