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Whilst it's true that companies sp don't always rise on approvals, there is no way that is happening with an approved AD drug.
Also often when it doesn't rise after approval it's because approval is already priced in.
Times article - Genetic trait that virtually ‘guarantees’ Alzheimer’s identified
Researchers have identified a genetic trait that makes it virtually “guaranteed” a person will get Alzheimer’s in a discovery that may pave the way to better targeted treatments and earlier diagnoses.
A study found that having two copies of a specific gene makes it almost inevitable that a person will eventually develop symptoms.
Experts said the discovery may help the development of targeted treatments and could enable genetic testing and earlier interventions.
More than 900,000 people have dementia in the UK, the majority of whom have Alzheimer’s. There is no cure for the disease, although treatments have been found to slow its progress.
In the study, researchers in Barcelona found that 95 per cent of people over 65 with two copies of the APOE4 gene variant developed signs of the disease. About one in four people in the UK have one copy of this gene, while one in fifty — equivalent to more than a million people — have two.
“This gene has been known for over 30 years and it was known to be associated with a higher risk of developing Alzheimer’s disease,” said Dr Juan Fortea, director of the memory unit of the neurology service at Sant Pau Research Institute, and lead author of the study.
“But now we know that virtually all individuals with this duplicated gene develop Alzheimer’s biology.”
The researchers said their findings effectively amounted to the discovery of a new genetic form of the disease, because the presence of both genes was such a useful predictor for the condition.
The findings, published in the journal Nature Medicine, are based on data from more than 10,000 people and more than 3,000 brain donors.
Siân Gregory, the research manager at Alzheimer’s Society, said: “I think it’s definitely a breakthrough for the field in terms of how we think about the causes of Alzheimer’s disease.” She said it would make it easier to predict when symptoms might start and enable doctors to give people more advice at diagnosis.
Dr Richard Oakley, Alzheimer’s Society’s associate director of research and innovation, said: “Understanding the causes of the disease in greater detail is vital and can unlock new ways of diagnosing, treating and caring for people affected by Alzheimer’s disease in the future.
“The insights from the study suggest that in the future it could be important to take into account a person’s genetics when planning how to reduce their risk of developing Alzheimer’s disease, or when considering their treatment if they already have the disease.”
Previous studies have shown that having at least one APOE4 gene variant almost triples the risk of getting the disease, while having two copies increases the risk by up to twelvefold.
In the latest research, a majority of people with two copies of APOE4 showed some signs of the disease by the age of 55. By age 65, 95 per cent of them had abnormal levels of a protein known as amyloid in the fluid that surrounds the brain and spinal cord, which is a key sign of Alzheimer’s disease.
Professor Tara Spires-Jones, president of the British Neuroscience Association and group leader at the UK Dementia Research Institute at the University of Edinburgh, said: “This study adds compelling data to suggest that people with two copies of this gene are almost guaranteed to develop Alzheimer’s if they live long enough and that they will develop Alzheimer’s earlier than people without this gene.”
Dr Víctor Montal, a researcher who studies the molecular structure of the APOE gene at the Barcelona Supercomputing Centre, added that the findings could be used to monitor people with this gene from an early age for preventive interventions. Drugs such as donanemab and lecanemab have been shown to slow the progression of the condition in clinical trials.
https://www.thetimes.co.uk/article/alzheimers-disease-genetic-cause-treatment-jgwwtcccn
The CHMP is involved in both the application eligiblty and the actual submission. The CHMP involvement is mentioned in section 2.2 here - https://www.ema.europa.eu/en/human-regulatory-overview/marketing-authorisation/pre-authorisation-guidance
Anyone tempted by Annovis? I am tempted but the cash situation keeps stopping me. I believe under $5 they can't raise more funds from their current ATM deal.
Well he got Dr Marwan Sabbagh to join in September as chair of the scientific advisory board. I doubt Sabbagh would have trouble getting the word out -
"Prof. Dr. Marwan Sabbagh, MD, is a behavioral neurologist in the Alzheimer’s and Memory Disorders Program at Barrow Neurological Institute. He is also a professor and the Vice Chair of Research in the Institute’s Department of Neurology. He is board certified in neurology by the American Board of Psychiatry and Neurology.
Dr. Sabbagh’s expertise includes the diagnosis and treatment of Alzheimer’s disease and other memory disorders. He is a fellow of the American Academy of Neurology.
Dr. Sabbagh earned his medical degree from the University of Arizona College of Medicine in Tucson and his undergraduate degree from the University of California—Berkeley. He completed his neurology residency at Baylor College of Medicine in Houston, Texas, and a geriatric neurology and dementia fellowship at the University of California San Diego School of Medicine.
Dr. Sabbagh is a leading investigator of many prominent national Alzheimer’s prevention and treatment clinical trials. He serves on the editorial boards of the Journal of Alzheimer’s Disease and Alzheimer’s and Dementia: Translational Research & Clinical Interventions. He is the editor-in-chief of Neurology and Therapy. Dr. Sabbagh is a prolific author who has written and edited books on Alzheimer’s disease and has contributed to hundreds of medical and scientific articles.
“I’m excited to join Anavex’s Scientific Advisory Board at this time of important progress of the Company,” said Professor Dr. Sabbagh. “There is such a significant unmet medical need around the globe caused by Alzheimer’s disease and given the robust clinical data of blarcamesine (ANAVEX®2-73) in Alzheimer’s disease I look forward to joining the scientific team at Anavex to move forward a path for patients and their loved ones to be able to provide an effective therapeutic which can be taken orally and is generally safe.”
IMO I'm guessing Anavex most likely recieved mixed/ambiguous feedback in regards to applying to FDA in 2023, especially in regards to ADL end point. Missling was perhaps going to wait for OLE data and/or the peer review (perhaps even hoping for the peer review to in part make the case that ADL was difficult to show in early AD trials).
Now with the change in FDA draft guidance if all this was the case that it seems things have obviously changed. Perhaps companies might still want to wait for the guidance to become official? Either way it would seem AVXL could apply to FDA anytime...they said they went with EMA first because that process takes the longest and the EMA pr's came out of nowhere last time so there may not be much warning beforehand.
Seems like the issues for annovis is the analysis they did wasn't pre-specified, the fact it's only based on 12 weeks and the ADL fail (though less of a problem with new FDA guidance) plus quite low cash. Also noticed they had about 50% screened out from being in the trial (though I suppose no worse than the BP trials).
On the 4th March video conference in the q and a part he mentions in a slightly jargled way they are in the rapporteur process and awaiting being assigned a co rapporteur.
When the second paragraph from the PR is added with the "early as possible in 2024" line it seems to sway it to saying "Given the focus on speed in the December PR and some lead time, it's reasonable to guess they might submit the application sometime between April and June 2024. However, the rapporteur details mentioned in March could cause a slight delay"
For what its worth when I copied into google gemini the December 2023 PR opening paragraph plus the fact that the company had 40 employees and the CEOs currently getting rappatour comments in early March it guesses a submission date between June and September 2024.
Maybe Bishop is confusing it with the peer review which Missling said "this year"? Bishop did seem a bit confused last time he was on a call.
Tom I hate to be rude but...could you not just say the price could go up or down?
But we already know it was significant...the Sept 2023 PR from Anavex (overseen by Dr Jin who has 25 years with FDA as a lead on AD trials) had ADAS COG with a p value of 0.026 i.e 2.26 in a 100 chance that the improvement was due to chance. The FDA draft guidance now states this is the end point they care most about now, not ADL as it's too difficult to show in early AD studies (though Missling did say ADL was trending in right direction in latest call).
Tootalljones the ADAS-COG end point (the one the FDA cares most about) was met with a 2.26 in 100 chance of it being due to chance and the reduction in brain volume loss was met with a 1 in 2,000 chance of it being due to chance, so I'm not sure why you are saying "no compelling evidence".
The other bears were criticizing the company for not having enough staff, you're saying they have too many.
Perhaps if in charge of a company that is about to submit applications for an AD drug in Europe/US and Asia that would mean huge revenues after having the FDA almost seemingly tailor their approval guidelines to suit the companies drug results it's difficult not to be a FOMO master?
Crescent yes I remember him saying something like that almost as an aside where I think he said something like "either in the peer review or the presentation" but can't remember where it was in the 30 min video now.
Dr Sabbagh talking at the American Academy of Neurology a few days ago (he became chairman of the scientific advisory board for Anavex in Sept 2023). https://www.linkedin.com/feed/update/urn:li:activity:7185618553235013632/
He says ADL was "trending in the right direction but not totally significant by itself". Obv have to take CEOs words with grain of salt but when you consider this and the other co primary being under p = 0.025 plus the secondary under p = 0.025 plus the brain loss reduction p - 0.0005 (5 in 10,000 chance the improvement was due to chance) plus the new FDA guidance almost like it's written for anavex with them saying ADL can take longer to show in early AD etc so end point not required, the mild side effects, the ease of taking a pill and the low amount of patients screened compared to other AD trials then it it all seems quite bullish in terms of the science. Just have to keep being patient.
Biochecker, are you sure it's wise to be invested in what you call "a charade"? Normally after the 300th negative post in a row about a company I would expect the poster to no longer be invested.
Treden I think you should be careful saying positive things or suggesting the share price could be higher in future, it seems to upset a lot of the "investors" here.
"Going to the $40's? Making excuses for the peer review delay? IMO that's a FOMO building pumping post."
He said if we get everything we want i.e peer review and EMA submission/FDA submission which could certainly all be in the next couple of months.
Market would then be a lot more focussed on predicted revenue etc in this massive market (obviously with discount factors for time and chances of approval - this has improved with FDA updated guidance)
I don't see how $40s would be that excessive, $45 a share would put market cap at around $3.7 billion.
Biochecker is there anything you view as bullish about your Anavex investment? Clearly you must be more bullish than bearish otherwise why would you be invested?
At-least if in the next couple of months Anavex announce the EMA submission and FDA AA submission (especially now with the better FDA guidance as mentioned in the presentation) then the stock should respond very nicely and as a loyal investor you will be rewarded Biochecker...I'm sure you will be celebrating with all of us.
"The problem for Anavex is that they are not using validated response biomarkers. We also don't know details - who was included/excluded, n. AB42/40 had p=0.048 so these points matter as no wiggle room."
According to google gemini there is an estimated 70% correlation between neocortical amyloid burden and plasma 42/40 and as Mayo pointed out - Blarcamseine performed ~73% better than Lecanemab at 52 weeks and about 60% better than Lecanemab score at week 72.
Donanemab failed to show effect against plasma 42/40, providing only a 2% over placebo.
Also talking about inclusion and exclusion I prob don't need to remind that Lecanumb excluded around 70% odd of their potential patients from the trial.
It's funny that for all the Anavex bashers whenever you ask them what drugs should an Alzheimers patient take instead they never have an answer. The FDA don't have the luxury of going quiet on this point, they actually have to find the best drug for patients even if it's not perfect because no drug nor drug trial is.
To me I don't see how the FDA can ignore a finding like patients on the drug having a reduction in brain shrinkage with a 5 in 10,000 chance of it being due to chance (p=0.0005) and that was before the updated favourable guidance.
Most of the bearish sentiment isn't based on the science it's based on the share price being down which is something that can change very quickly.
But no-one forced him to sell after Rett excellence failed, it wasn't the major part of the pipeline? There is risk and reward in shares and share prices fluctuate.
If people can sue anytime as aspect of a biotech outcome doesn't go their way that would be amazing deal, just get the reward but no downsides because you can just sue.
There is still is nothing in this lawsuit that is strong or tangible against Anavex' main goal which is AD that surely makes up most of the market cap.
A judge is not going to take some twitter quotes from a "bio tech journalist" very seriously, there are much more respected people on the Anavex team who clearly still believe in the potential for Blarcamesine.
It comes across as some disgruntled day trader wanting compensation, no-one forced them to sell and realize their loss after the RETT Excellence drop.
I don't really get the lawsuit...it seems to be only focussed on RETT which is arguably a minor part of the pipeline and the Excellence trial. It states that the stock fell 35% after the excellence read out, why sue Anavex for this though, sue the market makers for making it fall that hard?
I believe Missling mentioned the PDD data being in a peer review only once, whereas the AD peer review has prob been stated over 10 times in the last 6 months, it feels a lot more like it will happen.
"Some people seem to spend a ton of time here pumping and hating. A real study in anonymous human interactions on the internet."
I would say the more strange phenomena is the ones with apparently have no position in this company or even claim to be long who spend their free time posting mostly bearish comments here every hour or so.
If these people said they were short then this constant negative posting wouldn't be strange because they would be 'invested' so to speak, but not many on here ever seem to state they are short.
Managements fiduciary role is to get long term sp growth. Clearly that hasn't happened when compared with a year ago however in terms of looking ahead management aren't going to put out PRs just to boost the short term sp. If they believe peer review will be relevatively soon they will wait for the peer review publication. If people sell coz they are worried before the publication that would be tough luck on them but it isn't managements responsibility to massage investors short term concerns or worries about the share price variability.
Only time a company might care about short term sp would be if they wanted to sell shares for more company cash but Anavex has a decent amount of cash and no debt.
Why are the lawyers targetting Rett if Misslings handling of it "seems far less troubling than AD"?
He's not on ST, he's on Yahoo
Interesting...don't usually follow yahoo but purely based on looking at this persons posting history they seem fairly legit rather than someone who would make something up but can't say for sure of course.
"However, the FDA has acknowledged that it may take longer to establish clinically meaningful treatment effect among patients with early Alzheimer’s due to the very limited (if any) cognitive and functional deficits seen at those stages of disease. Additionally, many tools often used to measure functional impairment in patients with later stages of Alzheimer’s may not be able to identify subtle changes in early-stage disease, the agency explained.
Given these two factors, the FDA is considering other approaches, including endpoints based on cognitive assessments or surrogate endpoints, which may allow for shorter trial durations in the earliest stages of disease.
Direct measures of clinical benefit or validated surrogate endpoints may support a traditional approval, according to the FDA, while surrogate endpoints or intermediate clinical endpoints that don’t directly measure clinical benefit but are considered reasonably likely to predict clinical benefit may support the case for accelerated approval."
https://www.fiercebiotech.com/biotech/new-fda-guidelines-consider-amyloid-reduction-reasonably-likely-predict-clinical-benefit?utm_medium=email&utm_source=nl&utm_campaign=LS-NL-FierceBiotech&oly_enc_id=5901F6483778B1Z
People saying that the presentation is short at 15 mins but if it's mostly about the brain loss reduction finding of which we only really know the p value and have a visual of the the p values in different brain regions then it's hard to see how there wouldn't be new info with 15 mins mostly on this topic?
If as you say their drug candidate is no good can you say which are the "good" AD drugs patients should be having instead?
Dr Marwan Sabbagh clearly wasn't hired for RETT. He said the following: "I’m excited to join Anavex’s Scientific Advisory Board at this time of important progress of the Company. There is such a significant unmet medical need around the globe caused by Alzheimer’s disease and given the robust clinical data of blarcamesine (ANAVEX®2-73) in Alzheimer’s disease I look forward to joining the scientific team at Anavex to move forward a path for patients and their loved ones to be able to provide an effective therapeutic which can be taken orally and is generally safe.”
Even if there is not a perfect correlation it would seem overall studies recently have tended to find an around 60-80% correlation between plasma Aß42/40 and global amyloid burden measured by PET (according to google gemini). Therefore I would says it is worth more than a "regulatory side note". It would be rather crazy for Anavex not to mention the differences with competition even if not a perfect comparison.
Mayo noted on stocktwits that it did 73% better than Lecanemab at 52 weeks and about 60% better than Lecanemab score at week 72. So this wasn't a slim impovement even if only measuring something with a 70% odd correlation.
Obv this is ignoring the other biomarker of brain volume loss reduction in blarcamesine in the dosed group vs placebo with a 5 in 10,000 chance of this being due to chance. The Mabs instead shrink the brain quicker than placebo.
Yes that's the same chat GPT release I'm using. I am in UK but prob makes no difference.