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If not, is it logical to conclude that the results are not bad meaning good.
Or, is he precluded from buying if the results are bad?
Article 23 of regulation (EC) No 726/2004. ...establishes that the holder of a marketing authorization for a drug for human use must have a QPPV.
A reason for the hire may be: "When a company submits an application for permission to bring a medicinal product onto the market, the company submits a description of its system for monitoring the safety of the product in actual use (a pharmacovigilance system) and proof that the services of a QPPV are in place."
https://en.m.wikipedia.org/wiki/Qualified_Person_Responsible_For_Pharmacovigilance
Here is a better question: Why would Rocio Garcia Canamaq, the founder of Leon Research—Anavex’s CRO for the phase 2 PDD trial in Spain accept a position with Anavex if the trial in Spain is failing?
In the European Union, the Qualified Person Responsible For Pharmacovigilance (QPPV) is an individual, usually an employee of a pharmaceutical company, who is personally responsible for the safety of the human pharmaceutical products marketed by that company in the EU. This function was established in 2004 by article 23 of regulation (EC) No 726/2004. The article establishes that the holder of a marketing authorization for a drug for human use must have a QPPV. When a company submits an application for permission to bring a medicinal product onto the market, the company submits a description of its system for monitoring the safety of the product in actual use (a pharmacovigilance system) and proof that the services of a QPPV are in place.[1]
https://en.m.wikipedia.org/wiki/Qualified_Person_Responsible_For_Pharmacovigilance
How will biotech be affected long term post pandemic? Will drug approval become more liberal? (Gileald’s drug, remdesivir I believe failed its endpoint —lowering deaths—in the study, and the FDA let them change the measure from lowering deaths to shortening hospital stays from an average of 15 to 11.) Will the FDA now apply that standard to other drug trials? If you rush drugs through to treat people for a virus, should you rush approval of drugs for people terminally ill from cancer, central nervous system diseases, etc.? Gilead’s drug received emergency approval. Will emergency approval be applied to terminally ill patients? Will it be applied to diseases that create financial burdens for individuals and governments?
Vaccines for the C-virus and possibly other drugs to treat the virus will be rushed to approval as well. Will governments, the FDA, politicians, and society simply accept that the drug approval process revert to what it was before the pandemic? Will governments and others be more forthcoming with funding of drug trials to treat other devastating diseases? Will this experience change drug approval for better or worse? Thoughts? Ideas?
I think the stock market in general and the economy are two different things. indeed though, the economy may affect the stock market in ways that influence sentiment. The economy right now is lousy, but stocks have been rallying off March lows. What is causing this rally? Sentiment. Feelings may change on a dime, and the rally reverses. Yet, individual stocks may do well even in the decline of the stock market. Why? Because sentiment, judgment prompted by feelings, affects stocks individually. It also sways the price of tulips, gold, Cabbage Patch Dolls, guns, etc.
Why am I writing about this? Globally, all of us in this together, are focused on our health for survival. We are looking for biotech and drug companies to develop new vaccines and drugs to treat us for viral infections. We are optimistic they can do that. Otherwise, stocks like REGN, INO, and others would not be bolting upward. We are all looking for good news. Some of this hope and enthusiasm is likely rubbing off on AVXL as well, chiefly since the PDD trial mid-year news is drawing closer.
Tom, maybe this is being reflected in your charts?
Peter: Thank you very much. Your work is insightful and very helpful. I wish you the very best! Sokol
Oligomannate - George posted this in November 2019:
Post # of 248033
Sodium oligomannate therapeutically remodels gut microbiota and suppresses gut bacterial amino acids-shaped neuroinflammation to inhibit Alzheimer’s disease progression
https://www.nature.com/articles/s41422-019-0216-x
Quote:
The analysis was conducted using Ariana Pharma’s KEM® Artificial Intelligence, an FDA-tested technology to systematically explore combinations of biomarkers. Results revealed that patients treated with ANAVEX®2-73 had high levels of two gut microbiota families, Ruminococcaceae and Porphyromonadaceae, which were associated with improved activities of daily living (ADCS-ADL) at week 148 (p<0.01 and p<0.04, respectively).
http://www.arianapharma.com/wp-content/uploads/2019/07/Anavex-Microbiota-Presentation-AAIC-July-2019-FINAL-1.pdf
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/
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.
Talon: This is a letter I wrote the WSJ a year or so ago about the Biogen drug and Biogen’s partner, Eisai. I received a response. The WSJ agreed with me. This is what I wrote back then:
“They, Biogen and Eisai, obtained a different outcome with a new measure of efficacy. Biogen’s partner Eisai, a Japanese pharmaceutical company, came up with a new standard to measure ”success”. This ”success” measured by a new internally conflicted standard should by itself raise a red flag.
Even then this ”success” may not be so great considering their drug is an infusion and the same WSJ article points out: The study involved 856 subjects in the early stage of the disease. Among the side effects that the companies reported were reactions at the sites of the infusion and swelling around blood vessels observed with brain imaging.
Making multiple trips to a clinic or medical office for infusions as opposed to taking a pill poses difficulties in addition to the risks of adverse events, and for what: BAN240 does not stop or reverse Alzheimer’s. To sum up : IV injected, only works at highest dosage at if at all, takes 6 months to kick in, and the cognitive tests we're created in house and not standard. And, what percentage of adverse events occurred at this highest dosage? It would be of interest to know what percentage of those receiving ONLY the highest dosage, the one that reportedly works, developed adverse events.”
H. Hampel as we all know is now Vice President and Chief Medical Officer (CMO) of the Neurology Business Group at Eisai Inc. and is a member of the company’s Executive Committee for the Americas. Cite: https://www.researchgate.net/profile/Harald_Hampel
Note: Hampel was not with Eisai at the time I wrote the above letter to the WSJ. Therefore, he was not involved in obtaining a different outcome with a new measure as I pointed out in that letter.
With Hampel’s current position at Eisai , Hampel as CMO, is “... responsible for leading Eisai’s medical affairs strategy and technical expertise in neurology with the aim of advancing opportunities for innovation and continuous improvement. With more than 25 years of experience conducting clinical trials in Alzheimer’s disease (AD) and related neurodegenerative diseases, I (Hampel) am overseeing the planning and implementation of Eisai’s global neurology clinical trial programs. I am also responsible for developing the global neurology medical strategies for the company’s commercial products, pipeline assets and late-stage compounds approaching the commercialization stage...”
I like the part about Hampel being responsible for “strategy and technical expertise in neurology with the aim of advancing opportunities for innovation and continuous improvement... overseeing the planning and implementation of Eisai’s global neurology clinical trial programs...”. I also especially like the fact that he is responsible for “...pipeline assets and late stage compounds approaching the commercialization stage...”.
Thank you, Power.
Thank you, Tred, and I concur with your post.
Yes, autophagy is a factor. I saw a reference to that when doing some of the research for this post. Thank you, George.
This post lost its format. I-Hub somehow converts post eliminating separate paragraphs. It makes it difficult to read. I suggest cutting and pasting it in a word processor, restore the separate paragraphs, etc., and make it readable.
The PDD trial in Spain, and the exposure of PDD trial patients to Covid-19.
This is a two part discussion. In the first part, I include my rough analysis that indicates that the PDD trial may have substanitally progressed before Covid-19 was recognized as a problem. In the second part, I discuss Covid-19, the "cytokine storm" (the deadly Covid-19 event), and exposure of PDD patients to the virus.
1. PDD trial in Spain:
The Anavex PDD trial is a 120 patient, 14 week study in Spain (Europe) along with 3 sites in Australia.
1. First PDD patient enrolled patient - October 30, 2018. https://www.anavex.com/first-patient-enrolled-in-anavex-life-sciences-phase-2-clinical-trial-of-anavex2-73-for-the-treatment-of-parkinsons-disease-dementia-pdd/
2. Trial recruitment reaches half way mark - March 13, 2019. https://parkinsonsnewstoday.com/2019/03/13/anavex-life-sciences-reaches-50-enrollment-threshold-in-anavex2-73-parkinsons-disease-dementia-pdd-phase-2-study-ahead-of-schedule/
3. Achievement of full enrollment - Jan 27, 2020. https://www.biospace.com/article/releases/anavex-life-sciences-announces-achievement-of-enrollment-target-for-the-anavex-2-73-blarcamesine-phase-2-parkinson-s-disease-dementia-pdd-clinical-trial/
4. "To offer eligible participants of the Phase 2 PDD study access to ANAVEX®2-73 (blarcamesine), participants completing the trial may enroll in a voluntary 48-week open-label extension study." (Same reference as #3 above.)
I estimate that 75% or more enrollment was achieved as of August 2019 based on March 2019 50% enrollment achievement within a little less than 5 months after the first patient was dosed. In other words, 5 months and 1/2 after 50% was achieved, I am estimating that 75% enrollment was achieved by the end of August 2019. Therefore, by the end of December 2019, 14 weeks after 75% enrollment, the vast majority of patients 75% (90) or more patients should have completed 14 weeks of dosing of either AVXL 2-73 or the placebo. By sometime in May of this year, all patients in the PDD trial will complete the 14 week trial. However, more than 75% have now, as of April 2020, completed this trial. 100% may complete the trial by the end of May, assuming no interference from the C-virus.
It does seem that the Anavex PDD trial was and is far enough along so that any complications to this trial caused by the C-virus are likely not significant enough to invalidate the trial.
Some number of patients, probably at least 60, PDD clinical trial participants will complete dosing of AVXL 2-73, assuming 50% of the PDD patients receive AVXL 2-73 and 50% receive the placebo. More that 60 from the PDD trial will be AVXL 3-73 dosed, assuming some PDD placebo patients were switched to the real thing once they completed their 14 week regimen of the placebo. Additionally, I assume that a number of AD patients, at the very least those patients in the initial AD trials, continue to receive the drug. "Interim 2-Year (104)-Week) data from the Phase 2a ANAVEX®2-73 (blarcamesine) extension study, with Alzheimer’s disease patients followed for up to five years, will be presented at the 12th Clinical Trials On Alzheimer’s Disease (CTAD) 2019 Conference in San Diego, CA (December 4-7, 2019)." https://www.anavex.com/anavex-life-sciences-presents-anavex2-73-blarcamesine-data-at-12th-clinical-trials-on-alzheimers-disease-ctad-2019-conference/.
Seemingly, all of the 120 PDD clinical trial patients that complete the PDD trial, will have an opportunity to receive AVXL 2-73, Therefore, using only the PDD numbers and the number from the previous AD trials, unless we have a high drop out rate, we should have more than 100 or so PDD patients (potentially most of the PDD patients will receive AVXL 2-73 with voluntary enrollment in the extension study) during this year from which we may evaluate AVXL 2-73. The number is higher if we consider all patients in all AVXL 2-73 trials.
We all know what will happen if the PDD trial fails. We may have mixed results that leaves us uncertain, which would set us back. Hopefully, we will see a high percentage of success rate among PDD patients in this precision trial, but I am sure that arguments may be made that it is unrealistic, even if this is a trial for an unmet need, to expect approval of AVXL for PDD or any other disease based on this number alone. Even so, if the PDD trial is successful, this will be an attention grabber.
2. EXPOSURE OF PDD TRIAL PATIENTS TO COVID-19
Potentially, patients in Anavex's clinical trials have been exposed to Covid -19. My question is: How have Covid-19 infected clinical trial patients fared? I ask this question because it has been intimated that AVXL 2-73 has a beneficial impact on neurological inflammation.
Inflammation is the major problem causing deaths in Covid -19 patients. It is sometimes referred to as the "cytokine storm". This virus adversely impacts the central nervous system and organs throughout the body. Here is a list of articles about the "cytokine storm'', inflammation caused by the C-virus, and the adverse impact of the virus on the central nervous system.
1. WSJ article "Haywire Immune Response Eyed in Coronavirus Deaths, Treatment - Researchers are looking at treatments to suppress ‘cytokine storm,’ increasingly linked to the most severe Covid-19 cases"
Haywire Immune Reaction Linked to Most Severe Cases
2. Pro-inflammatory cytokines in Alzheimer's disease].
Stamouli EC1, Politis AM1.
Author information
Abstract
Alzheimer's disease (AD), the most common progressive neurodegenerative disorder in the elderly, is clinically characterized by progressive impairment of cognitive functions, including reduced critical capacity, weakness of decision-making and problem orientation, while in the more advanced stages it is accompanied by behavioral disorders and impaired verbal ability. Neuropathological characteristics of the disease are the neurofibrillary tangles (NFT), the neuritic plaques (NP), the prominent synaptic loss and eventually the neuronal loss. The presence of inflammatory process seems to be playing important role in the progression of the disease. This process is directed by the activated glial cells and it leads to the overproduction of acute phase proteins, complement factors activation and induction of inflammatory enzyme systems. These inflammatory factors can contribute to neuronal dysfunction and cell death. Cytokines belong to the acute phase proteins, which are secreted from glial cells. They can either strengthen the inflammatory reaction or suppress it, adjusting the intensity and duration of the immune response. In the category of cytokines belong several interleukins (ILs) and various factors (TNF-a, TGF-ß). Interleukins are involved in complex intercellular interactions among neurons, microglia and astrocytes, as well as intracellular signal transduction events, which are necessary to promote the inflammatory cascade characteristic of AD neuropathology. It has been observed that increased levels of pro- inflammatory cytokines, including tumor necrosis factor (TNF), interleukin 1ß (IL-1ß), interleukin 6 (IL-6) and interferon ? (IFN-?), may suspend phagocytosis of amyloid Aß in brains of patients with AD. Thus, it may interfere with the effective removal of plaque from microglia, promote astrogliosis and neural death. Normally, during immune surveillance, a balance is maintained between pro- and antiinflammatory influences. Yet, during AD, the abnormal accumulation of soluble amyloid oligomers triggers excessive release of pro inflammatory factors, such as cytokines and other acute-phase reactants, out of proportion to the regulatory components, such as IL-4, IL-10, receptor antagonists, interleukin inhibitors and others, ultimately leading to neuronal and synaptic injury and loss and cognitive decline. These changes in the brain parenchyma are often accompanied by changes in levels of these inflammatory proteins in peripheral blood. Even though literature is presenting conflicting studies, efforts are being made for the detection of cytokines in peripheral blood and association of their levels with the progression of AD. Inflammatory pathways, involving the signaling of cytokines, could be potential targets for the prevention of AD and the development of new therapies. The aim of the present work is to review studies indicating a correlation between these inflammatory agents and AD pathogenesis.
https://www.ncbi.nlm.nih.gov/pubmed/28114090
3. These slides were used at the Anavex July 2019 presentation:
http://www.arianapharma.com/wp-content/uploads/2019/07/Anavex-Microbiota-Presentation-AAIC-July-2019-FINAL-1.pdf
See specifically the slide entitled: SIGMAR1 Restores Homeostasis Caused by Neuro-inflammation
https://www.anavex.com/wp-content/uploads/2019/12/CTAD2019_ANAVEX2-73_P84_Microbiota_.pdf
4. These articles touch how the C-virus may invade and effect the central nervous system:
A. "Lost Smell and Taste Hint COVID-19 Can Target the Nervous System"
https://www.the-scientist.com/news-opinion/lost-smell-and-taste-hint-covid-19-can-target-the-nervous-system-67312
B. "The Surprising Neuroscience of COVID-19
Effects on the central nervous system might contribute to respiratory failure."
https://www.psychologytoday.com/us/blog/long-fuse-big-bang/202003/the-surprising-neuroscience-covid-19
It is reported that recovered C-virus patients have lingering effects from the virus and potential damage to their bodies, including the central nervous system. We have a long way to go before we know about any of this, but there is a need for treatments for complications in recovered C-virus patients. What those drugs may be is anyone's guess, and I do not wish to give anyone the impression that AVXL 2-72 may be one of those drugs. AVXL 2-72 has not yet been approved for any use, it has not been studied for Covid-19 treatment or prevention, and it is unrealistic to speculate about whether it will ever be available for or of any use in treating recovered C-virus patients.
Lastly, I raise the question of why it is that Covid-19 is more deadly among the elderly population? Is it because of underlying diseases that come with age? Is it due to degeneration of the body and its ability to maintain internal stability (homeostasis)? Why do some young people that otherwise appear healthy die from Covid-19? If we have a drug or drugs that helps to restore homeostasis of the central nervous system, may it be of use (not now for Covid because there is not enough time to test for that) prophylactically in the future to prevent diseases and infections from developing?
We have a long way to go, and we have many interesting things to explore.
Inverted head and shoulders bottom (daily chart)?
It is traditionally said that when the U.S. dollar drops, gold rises. My opinion, do your own DD though, is that the dollar will likely continue to rise, but gold will rise as well with the massive stimulus, etc. You must note that global debt is denominated in U.S. dollars. Global debt is massive, and it is a huge problem. The U.S. dollar is in demand because global debt is repaid in U.S. dollars at a time that currencies worldwide are devalued in terms of dollars. With world currencies weakening, gold is in demand, and gold is holding up well as Bigworid points out.
Bigwoid also points out that stocks may decline further. I think that is highly likely. The U.S. is a debtor nation. It is very much unlike Japan, which is creditor nation. When U.S. dollars are needed foreigners will also be selling U.S. securities as needed.
U.S. is a debtor nation - Foreigners own more U.S. assets than we own foreign assets. This matters because foreigners have two ways to get dollars when they really need them. They can participate in international trade, or they can sell their U.S. dollar-denominated assets. In healthy markets, they choose the first option - international trade. However, during a global recession, that trade disappears. Therefore, when dollar debts need to be paid, they are will need to sell U.S. assets for dollars.
There are other reasons why U.S. securities will continue to be in trouble even though you see “false rallies”.
An important factor is you can kiss buy backs goodbye, and corporate buy backs were the big factor in the stock market rise up until now.
Added to this situation is the massive global debt, the global pandemic, and an oil war between the Saudi's and Russia, two of the worlds biggest oil producers. However, the oil problem may be remedied for now depending on the meeting this Thursday. Reportedly, Russia and Saudi are close to a deal...
We shall see.
ElsaSara: Salud y riqueza!
Anavex does not burn $27.5 per quarter. It burns more like $5 million per quarter. It had $27.5 million on hand year end 2019 as I previously pointed out. In addition, it receives other funding as I pointed out. Anavex may have raised additional cash when its share price was higher earlier this year; however, even with the cash on hand at year end, it had/has adequate funding to carry it past the first quarter of 2021, and it will be receiving additional funding between now and then. In any event, let’s wait and see what the financial situation is next week, April 7.
Coronavirus cases in Spain may be slowing, the country's foreign minister has told the BBC.
https://www.bbc.com/news/world-52092898
Anavex is well funded. As. Xena says it has no debt. Anavex had a cash balance of $27.5 million at year-end 2019 and burns through about $5 million per quarter. It receives non-dilutive grant money from the Australian government and other sources that extends its cash runway through all of 2021.
To Missling’s critics:
"It is not the critic who counts; not the man who points out how the strong man stumbles, or where the doer of deeds could have done them better. The credit belongs to the man who is actually in the arena, ....who strives valiantly; who errs, who comes short again and again, because there is no effort without error and shortcoming; but who does actually strive to do the deeds; who knows great enthusiasms, the great devotions; who spends himself in a worthy cause; who at the best knows in the end the triumph of high achievement, and who at the worst, if he fails, at least fails while daring greatly, so that his place shall never be with those cold and timid souls who neither know victory nor defeat."
Teddy Roosevelt
Bio:
Thank you for bringing this to our attention. I had forgotten about the neurological disorders that may be caused by Zika and other viruses. This article you cite is of particular interest to me since my sister died at the age of 22 from encephalomyelitis and the neurological problems caused by that disease.
These are desperate times. People are frightened by the spread of Coronavirus. Notably, we have also seen a dramatic impact taking place in the stock market. Societies and governments, unfortunately, often do not respond except when faced with a crisis. We are, at the very least, on the verge of catastrophe with the Coronavirus virus that is also inflicting economic damage and political consequences.
AVXL 2-73 has passed safety tests. If AVXL 2-73 clinical trials continue to show promise for AD, Rett, then PDD with numerous scientific articles also indicating that it may be beneficial for other diseases; this may help in the approval of the drug. Or, at least it may mean more financial backing to move AVXL 2-73 forward. See also Plexrex's post this morning that quotes Kevin Francis, Ph.D., with Sanford Research: "And yes I agree, Anavex’s portfolio of compounds has a lot of potential for a number of conditions. My hope is we can apply some of these products to a number of diseases..."
In desperate circumstances, people abandon their usual complacent concerns such as, in the case of drug testing, following the traditional slow and cautious drug approval process. And after all, AVXL 2-73 is safe. It shows promise in helping to combat serious disorders, and it should be of even more interest as we face a potential pandemic with no known drugs available to be of much, if any benefit.
AMSTOCKS:
Excellent! Thank you.
Yesterday’s announcement is potentially very serious for AAPL. No one knows the extent of the virus problem except we know one thing. It is not over. First, Apple has derived a good percentage of its revenue from sales of its products in China, and second its supply of products has been disrupted. Just like a recession, there is a psychological response to a large scale virus outbreak. You can re-open stores and businesses in China, but you cannot force people to come. People will return when they think it is safe to return. Apple has opened stores, but customers have not decided to return. You can certainly understand why - especially in China - when the government responds the way it has. Seizing people with the suspected virus and throwing them in an enclosed container in the back of a pickup is one vivid example that stands out in the minds of everyone. The government’s response has made the problem worse, both literally and figuratively. Even if the virus begins to wane, the psychological impact will remain for a while. It is not likely to go away over night.
Fireman: Forbes article - Tom Bishop agrees the odds are in our favor:
“Tom Bishop, BI Research
Anavex (AVXL) is a bio-pharmaceutical company that amazingly few know about, but those who do are passionate about. Its lead drug is Anavex 2-73 (A2-73), an orally available drug with a clean safety profile that gives every indication so far of being highly effective against Alzheimer’s disease.
I’ll explain. Though there are 4 drugs approved, none of them really works beyond 6 months. It is currently in a 1-year, 450-patient Phase 2b/3 Alzheimer’s trial that is halfway through enrollment. If successful the company will file for provisional approval.
In an earlier, smaller Phase 2 study, comparable patients in the ADNI data base not taking Anavex 2-73 saw 4 times the deterioration in their Activities of Daily Living (ADL) scores as those protected by the higher dosage of Anavex 2-73 after two years.
In Anavex’s Phase 2a trial the high dosage of A2-73 cohort saw only a 3-point decline in ADL score (a normal score is about 70 or better) as compared to a 25 point decline (8 times the decline) in the low dosage group (that basically did not work so was effectively a placebo) at 148 weeks.
Same story with the Mini Mental State Exam (MMSE) score (perfect is 30, in this realm scores run below 26) where those taking the higher dose of Anavex 2-73 saw a drop of 1.1 in the MMSE score over two years vs. a drop of 4.4 in untreated patients.
This is phenomenal. Nothing on the market today can come even close to this and if the company can prove this in the Australian trial it will be on track to become the lead Alzheimer’s drug in a market that is at least $10 billion worldwide.
Proof of the pudding, 94% of those who have completed the current 1-year trial period are voluntarily continuing to take A2-73, and some (from the earlier Phase 2a trial) have continued for as much as 3 to 4 more years now. Sometimes that speaks louder than the hard data.
In addition, Anavex is currently wrapping up a Phase 2, 120-patient study with A2-73 for Parkinson’s dementia and is working on three Phase 2 trials for Rett Syndrome, a devastating disease that strikes girls in infancy handicapping them severely in almost every function.
Data from these trials are expected in 2020. I could go on for pages. There are no guarantees on Wall Street, but I hope you will agree that the above at least stacks the odds in our favor.”
https://www.forbes.com/sites/moneyshow/2020/01/03/7-hot-drug-stocks-to-buy-in-2020/#1693184c392c
However, we know even more since this article was published in Forbes.
“Placebos Can Also Produce Side Effects
Conversely, individuals can experience negative symptoms as a response to a placebo, a response that is sometimes referred to as the "nocebo effect." For example, a patient might report having headaches, nausea or dizziness in response to a placebo.”
How the Placebo Effect Works in Psychology
By Kendra Cherry Reviewed by Amy Morin, LCSW Updated on January 13, 2020
https://www.verywellmind.com/what-is-the-placebo-effect-2795466
I doubt it will hurt the clinical trial. I would argue too that untreated patients and treated patients still do not know if they are taking a placebo or AVXL 2-73. Not all patients taking the actual drug have side effects, and some patients taking the placebo do have side effects. There is no evidence the patients have been informed about what they are taking. Even before the MacFarlane statement patients taking the placebo and experiencing side effects believed he or she has taken the real thing, and those patients taking the real thing that do not experience side effects may conclude they have not been administered AVXL 2-73.
I certainly agree with “where she stops....no body knows”.
Of course.
Yes, of course, I read that before I posted that along with other statements by the company, NNVC.
NanoViricides Confirms It Has Been Working On A Treatment For The Novel Wuhan Coronavirus
"We have already initiated a program for developing a treatment for the 2019-nCOV," said Anil R. Diwan, PhD, President and Executive Chairman of the Company, adding, "Our platform technology enables possibly the most rapid pathway for new drug development against viral diseases. Of course, we will need support from governmental and international agencies such as the US CDC, WHO, and Chinese CDC to successfully develop these treatments, and, if developed, to get them to the patients in the fastest possible time. At this time, the Company does not have a collaboration with any of these agencies, and we have not been contacted by any of these entities or asked to develop a treatment for this virus. We had collaborations with the CDC and USAMRIID in the past. The Company intends to pursue a relevant collaboration for testing of our drug candidates soon."
The new 2019-nCoV is known to be closely related to the SARS-CoV of 2002-2003 epidemic. In fact it has been shown to use the same cell surface receptor as SARS-CoV, namely ACE2.
"We have already found some lead candidate ligands in our chemical library that can bind to the SARS-CoV spike protein in the same fashion as it binds to the cognate receptor, ACE2, using molecular modeling tools," explained Dr. Diwan, adding, "We believe this means we may already be significantly ahead in developing a potential treatment for the new Wuhan virus."
https://finance.yahoo.com/news/nanoviricides-confirms-working-treatment-novel-232000756.html
Yes, patients, caregivers, and health care providers all had positive comments including modifying the disease, becoming motivated and functional again - reading, painting, woodwork(?), etc. Real World Evidence. The following is some of what I posted before, but it it relevant to the find by TTT (thank you TTT):
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/
Yes, if a patent is listed in the Orange Book for a brand name drug, the FDA will not approve a generic version of that drug. The FDA acts in a minesterial capacity, and it does not determine the validity or enforceability of patents, it merely maintains the Orange Boook and list patents according to its procedural guidelines/applications, etc.
Every clinical trial that has ever been conducted begin with an hypotheses and a hope. Hypotheses are necessary and nothing new has ever been accomplished without hope. Hope is necessary because absent hope nothing will be tried - no action will be taken.
Controvesy and doubt exist in every instant where a new hypothesis is being tested. Innumerable examples exist. Take smallpox by way of only one example.
https://www.tandfonline.com/doi/abs/10.1179/isr.2001.26.2.125
“From its introduction in 1798, smallpox vaccination was always the subject of fierce controversy, particularly in England, where waning immunity from the first vaccinations coincided with government attempts to enforce compulsory vaccination. Unfortunately some supporters of vaccination tended to exaggerate its safety and benefits, while opponents equally played up the dangers and failures. Although some critics had legitimate concerns about safety and the duration of immunity, others denied that vaccination had any value at all, and claimed that its only effects were dangerous. This story has been told many times as a battle between government interference and growing demands for freedom of the individual from an increasingly articulate public – an early manifestation of the 'nanny state' and reaction against it...”
It seems that some things never change. Despite the value of vaccinations for society as a whole, we continue to witness opposition to vaccinations to this very day. Some of the diseases that we thought were elimated are beginning to recur because of the refusal of parents to vaccinate their children based on some beliefs that vaccinations are dangerous, etc.
Returning to the subject of treating AD, the hypothesis that has repeatedly failed so far is one based on amyloid plaque removal. However, this hypothesis remains based on hope that one day it will somehow be proven to be effective in some sort of clinical trial. We will have to wait and see about this, and we will have to wait and see about whether Anavex’s hypothesis bears fruit in treating CNS diseases, including AD and others. In the meantime, we must have hope, or we may abandon an hypothesis that proves to be beneficial. In my opinion, I think we should be thankful that Pasteur and others did not in the face of fierece criticism abandon their theories about vaccinations.
Falconer: Agreed. Thank you.
Thank you. I try to have lower expectations for my investments because of the many variables and risks involved in startup biotech investing.
Understood. Thank you. As a start, what I have done in the past for other drugs is attempt to determine what exclusivity in the U.S. for that drug may mean. In other words, I suppose you may use for comparison the sales of Donepezil in the U.S. to estimate what the sales of AVXL 2-73 may mean for Anavex in the U.S. alone. You may add other countries or continents (Europe for example) to that calculation after that, but I think starting with the U.S., the most lucrative market, makes sense.
The global Donepezil market is valued at 920 million US$ in 2018 and will reach 880 million US$ by the end of 2025, growing at a CAGR of -0.6% during 2019-2025.
North America is the largest consumption region of Donepezil, with a sales market share nearly 37% in 2017. Europe is the second largest consumption region of Donepezil, enjoying Sales market share nearly 29% in 2017.
Donepezil was developed by Eisai and Pfizer and is sold as a generic by multiple suppliers. Remember, however, that Anavex 2-73 will not be sold as a generic for the period that Anavex has exclusivity. Therefore, AVXL 2-73, if approved, will have sales in excess of the generic suppliers of Donepezil. Once a brand name drug goes generic, the price of that drug may drop as much as 80%.
Sales of AVXL 2-73, if approved in the U.S., may conservatively be estimated to be $350-$550 million. Sales in the U. S. and Europe upon apporval may conservatively be estimated to be $550 million to $1 billion. $1 billion is considered to be blockbuster status. Of course, all of this is conjecture, and it depends on the efficacy of the approved drug. However, my rough calculations are for AD alone. If AVXL 2-73 is approved for multiple uses, sales of the drug should exceed $1+ billion.
Total profits on brand-name drugs are higher than generic drugs, as companies retain exclusivity for a certain time period once the drug is approved by the Federal Drug Administration. Profit margins vary. According to an old WSJ article that I do not have the citation for: “At the manufacturer's level, prescription drugs can be enormously profitable for makers of both branded and generic drugs. Although gross profit margins vary widely, branded pills can have a margin of 90% or higher at the manufacturer's level, while generics can have gross margins of 40%, analysts say.” If we assume evenutal sales of approved AVXL 2-73 in the U.S. and Europe to reach $1 billion and a 75% profit margin, Anavex would conservatively obtain profits of $750,000,000.
If we further assume that Anavex has 100,000,000 shares outstanding at that point (roughly double what it has now), that would mean a profit of $7.50 per share. If we assume a price earnings ratio of 10 for Anavex, that would then provide a price per share of roughly $75.00. I caution everyone to not rely on this very speculative calculation. The assumptions made here may not turn out to be true. Even if something like this turns out to be true, it will occur, if at all, in the future — meaning it could be years in the future. I doubt that many “traders” or “investors” are willing to endure the ups and downs of Anavex over a number of years. Therefore, most shareholders will never realize much, if anything, in the way of a return on this company even if the company is able to gain approval. An investment in Anavex bears an extremely high risk, and I have no idea what the chances are that it will ever be successful. Any investor in Anavex should be prepared to lose all money placed at risk.
Yes, Anavex has competent patent counsel. I believe it is doing the best it can for patent protection. In addition to patent protection, Anavex may obtain some statutory or regulatory exclusivity. If efficacy is proven, Anavex will have some form of exclusivity in the U.S. — possibly elsewhere as well. The U.S. is the most lucrative market.
Patent protection is governed by the Patent and Trademark Office and generally runs 20 years from the date of filing (there may be some extensions of the 20 year period and some I mention below). FDA approval involves varying periods of exclusivity as follows:
Orphan Drug (ODE) - 7 years
New Chemical (NCE)- 5 years
"Other" Exclusivity - 3 years for a "change" if criteria are met
Pediatric Exclusivity (PED) - 6 months added to existing Patents/Exclusivity
Patent Challenge – (PC) – 180 days (this exclusivity is for ANDAs only)
Of course, it would be best to eliminate any patent challenge whatsoever and to obtain as much patent coverage as possible world wide, but anyway you look at it Anavex has significant exclusivity.
Yes. The Patent Cooperation Treaty is an international patent law treaty, concluded in 1970. It provides a unified procedure for filing patent applications to protect inventions in each of its contracting states. A patent application filed under the PCT is called an international application, or PCT application.
As of June 2018, ”...the PCT includes 152 member countries. In the words of WIPO Director General Francis Gurry, the PCT is a “truly a global system and a global treaty” that is at “the center of worldwide patenting activity.”
https://www.wipo.int/wipo_magazine/en/2018/03/article_0001.html