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FWIW—ANVS results-
Adam Feuerstein
@adamteuerstein
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$ANVS CEO Maria Maccecchini, on a call last night, admitted the failure of its buntanetap Parkinson's study:
The primary endpoint was MDS-UPDRS Part Il in the ITT population n=523
Maria: "This is the ITT population before subdividing them into the groups. And if you look at MDS-UPDRS Part II, you see that it pretty much doesn't move. The total ITT population does not change at all in MDS-UPDRS Part I!."
MDS-UPDRS Part Ill is the most important secondary endpoint. It also failed.
Maria: "Now, the MDS-UPDRS Part Ill part in the ITT population looks pretty much identical to the ITT population in our Alzheimer patients, everybody improves because that's what we see. We had high placebo, we had good response. Minus 3 is excellent response, but the placebo also has minus 3."And below is the Annovis graph showing the failure. Lowered scores in MDS-UPDRS means improvement. Placebo performed better than butanetap.
This is why Annovis is falsely touting a win on a small subgroup of study participants with a Parkinson's diagnosis of greater than 3 years. The analysis is invalid and will be laughed out of the FDA if the company tries to file on it, but that's a story for another time.
Another IGGY to add to my list! Blaa blaa blaa blaa, Missling has a bad suit , his hair is too long, their website is bad. Blaa blaa
.23 ….umm …. Is someone going to tell him?
George, it’s.23 not.023
I am really surprised that the bashers have not jumped on the issue of Anavex claiming for the past year that “all end points were met”
All that really matters is what the EMA and FDA think.
Looks like things are changing at Anavex.
Dr. Sabbagh and Dr. Jin Kun with be doing the twe presentations at AAIC this year.
These two Dr’s are well respected, experts in their fields and will no doubt have a better credibility with the AD KOL’s in attendance.
Kun Jin, PhD, Anavex Life Sciences also presenting on Monday, July 29th AAIC-
Improve Statistical Efficacy Interence: Global Reduction Rate in Disease Progression
Guoqiao Wang, PhD, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA and Kun Jin, PhD, Anavex Life Sciences, New York, NY, USA
Abstract/Proposal
I Monday, July 29, 2024
© 8:00 AM - 8:45 AM
• 118 ABC (Pennsylvania Convention
From the AAIC PR-
“The blarcamesine group demonstrated improvement compared to the placebo group in all clinical endpoints at 48 weeks: when comparing least-squares mean (LSM) change in ADAS-Cog13 score (difference, -1.783 [95% CI, -3.314 to -0.251]; P = 0.0226), LSM change in ADCS-ADL score (difference, 1.019 [95% CI, -0.66 to 2.70]; P = 0.234), LSM change in CDR-SB score (difference, -0.456 [95% CI, -0.831 to -0.080]; P = 0.0175), and LSM change in CGI-I score (difference, -0.285 [95% CI, -0.474 to -0.095]; P = 0.0033). Participants with =1 serious treatment-emergent adverse events (TEAEs) occurred in 56 participants (16.7%) in the blarcamesine group and 17 (10.1%) in the placebo group. Common treatment-emergent adverse events included dizziness, which was mostly mild to moderate in severity.
Conclusion:
In this phase 2b/3 randomized clinical trial, we found that among participants with early AD, blarcamesine significantly slowed clinical progression on prespecified primary outcome global and cognitive measures at 48 weeks in the ITT population. These results suggest that blarcamesine may be an effective, safe, and novel scalable oral treatment for early AD.”
Welcome back Hoskuld, I really missed your contributions to the board!
The Rett results was definitely a disappointing , unexpected setback.
More from stjernerogvann on ST-
$AVXL my thoughts on the meeting yesterday:
- I have been concerned about all P3 trials to date being underpowered and CM addressed that yesterday IMO by acknowledging the new Rett trial needed to have 2x the # of patients and be more balanced. My expectation now is that the PD trial upcoming will be properly powered.
- CM reiterated that the EMA saw the data and asked for the MAA submission. The rapporteurs have been assigned on schedule and there is no reason to think MAA submission should go past September unless the OLE data and analysis is critical and not complete by then.
- While CM said 3-71 trial is ahead of schedule, even saying it could be complete by YE, I don't think anyone should assume that will actually happen.
- 3-71 will be tried on AD - supposedly soon.
- Peer review: CM was confident this will happen soon, but, I am not counting on it. I do think CM believes (and the EMA believed) that the data is excellent. But, I have no opinion about when/ if paper will be released.
More SHM notes from stjernerogvann on stock twits-
1. CM said we should assume by YE for MAA filing...but CM also suggested that was a CYA date. FWIW, 07SEP2024 should be around the date of filing if we follow the regulatory timeline breadcrumbs.
2. CM said the paper that will be released will make us happy. Great data across the board (endpoints, biomarkers, MRI) and we will be happy with the dose dependency, too.
3. OLE info will be a key component to the filings.
4. There is a Rett conference this week and something should be announced there (probably regarding new trial.)
5. The new Rett trial will be 2x as large as the last trial, will have a larger % of placebo patients, and the inclusion/exclusion criteria will be slightly modified based on lessons-learned.
Steady, I just relayed the post from stjernerogvann on stock twists,
I would be interested in your thoughts on the comments from meeting. Any surprises?
Notes from SHM stjernerogvann from ST-
SAVXL notes from today's ASM:
1. Paper due before MAA
2. MAA should come before end of SEP but could slide to YE
3. Cohort 1 referred to low dose Part A group in 3-71 schizophrenia trial - high dose cohort also accrued and dosed now. Part B coming up. Possible completion by YE.
4. PD and Rett trial should start this year.
5. Autophagy is key component of MOA
(Sigmar1 promotes autophagy, the recycling of underperforming or unhealthy cells)
6. They have not met with FDA since end of P2/p3 - plan to do so when they have OLE data/analysis and can show the same data that MAA has seen
If more occurs to me then I will add later.
New insider purchase-
Peter Donhauser purchased 2835 shares on 6/14/24.
Not large but good to see!
https://archive.fast-edgar.com/20240617/AN2ZVQ2CX222UZR222232ZE26DA6Z2229862/
Plex, Let’s see what happens when the peer review paper is published.
If a reputable publication such as NEJM or Nature publishs a positive, detailed report on the p2a/3 results and it’s MOA, it “SHOULD” get everyone’s attention.
We shall see. Keep in mind this is a very disruptive drug in the CNS space and a lot of BPs and other parts of the CNS complex that stand to lose billions if Anavex is successful.
Alberto Espay's Post on Linkin-
Alberto Espay
Professor of Neurology, Advocate of precision me...
11h • Edited
Open Letter To My Dear Alzheimer's Patients
Like the FDA-approved lecanemab (Leqembi), the soon-to-be-approved donanemab will not improve you. You might worsen slower than if you were not on this infusion, but by so little, you won't be able to notice it. On the other hand, you have a 1-in-3 chance of having side effects, including a 1-in-4 chance of getting brain swelling, brain bleeding, or both (we doctors sanitized these under the acronym
"ARIA," for "amyloid-related imaging abnormalities").
Also, your brain will shrink faster. A smaller brain is of great concern. There has been little transparency about what this means in the long term, but can't be good.
The attached figures give you the full perspective: the risks are high, whereas any benefits are elusive or minuscule.
You may have heard these infusions are "better than nothing" and a "first step." Sometimes, doing nothing is best. Improving nutrition and exercising are more desirable to satisfy "do something" urges. Even the old and modest donepezil (Aricept) is twice as effective as lecanemab.
Lecanemab, donanemab, and other treatments developed over the past two decades aim to remove amyloid from the brain. Amyloid is the brain's normal response to various things we get exposed to as we age, not the cause of Alzheimer's disease. Most people with amyloid in their brains do not have Alzheimer's. Removing amyloid creates the illusion of progress but does not address the underlying causes or improve memory.
One last thing. Although your health should always come before any financial considerations, lecanemab infusions are highly profitable for hospitals and doctors like me. They can also drain a family's savings and strain Medicare. We could break the bank if a treatment makes a real difference. This is not worth it.
With love, Alberto Espay, MD
Powerwalker , do you know what ever happened to Hoskuld? I know he stopped posting here after the Rett results.
Great response! You are so right… thanks ,very helpful!
So only negative posts are acceptable.
itsthrillhouse on ST-
SAVXL if OLE is good, and EMA approves, but FDA looks at an empty 3 decimals of tail end probability on brain volume and *still* requires more trial, they are doing that for one reason and it's not the assurance of verifiable science.
Earlbefree from Stock twitz-
$AVXL so far in 2024 the CHMP has issued 48 opinions, 47 positive and 1 negative. MAA submitted, only thing ! want to hear. Bullish
Looks like Tom Bishop might have hit a nerve at the last cc!
“Some welcome news. A very small amount but still ok. Lets see some more of the executives join in.
https://archive.fast-“edgar.com/20240517/AB2ZLG2CX222OZO2222P2ZE299RTZ2229I62/
Reddit.. AMC, GME
IMO . Dr. Jin and his team has been having discussions with the FDA about the new AD guidance and the path forward for Anavex.
Maybe it’s just a coincidence that after almost two years after the ph2’3 AD trial completion, Anavex finally revealed the ADCS-ADL endpoint miss at the same time the FDA dropped it from the new guidance.
Interesting details on the new FDA AD guidance-
IV. OUTCOME MEASURES
Both clinical outcome assessments and biomarkers* should be included in clinical trials enrolling subjects with AD Stages 1-3; however, the approval pathway may differ based on the selection of the primary endpoint and its ability to measure a clinically meaningful change. Direct measures of clinical benefit or validated surrogate endpoints may support a traditional approval.' Surrogate endpoints or intermediate clinical endpoints that do not directly measure clinical benefit but that are considered reasonably likely to predict clinical benefit may support an accelerated approval® (see section IV. C.). Under the accelerated approval pathway, postapproval trials have been required to verify and describe clinical benefit.
A.
Clinical Endpoints
Historically, studies to support approval for drugs in the overt dementia stages of AD (Stages 4 through 6) have used an approach which required the assessment of both cognitive and functional (or global) measures as co-primary endpoints. The co-primary endpoint approach was used, in part, because the cognitive assessments used in the studies were not considered inherently clinically meaningful. Conventional approaches to assessing the cognitive deficits of AD use highly sensitive formalized measures of neuropsychological performance directed at particular domains that are capable of discriminating small changes in cognitive measures that may be of uncertain clinical meaningfulness when assessed alone. This approach was typically used in the setting of a therapy intended to treat disease symptoms in later stages of AD (i.e., Stages 4 through 6) and was intended to ensure that a change on a cognitive assessment was accompanied by an observed functional benefit, and alternately, that any observed functional
4 For definitions of clinical outcome assessments and biomarkers, refer to the BEST (Biomarker, EndpointS, and Other Tools) Resource, available at https://www.ncbi.nlm.nih.gov/books/NBK338448.
for serine distin sues and halogies May all, please see the guidance for industry Expedited Programs
"Section 506(c)(I)(A) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 356(c)(1)(A)).
Contains Nonbinding Recommendations
Draft — Not for Implementation
benefit could be attributed to a benefit on cognition and was not attributable to changes in other conditions. This remains a generally acceptable approach for stages of AD with detectable cognitive and functional impairments (Stages 3 and higher). Using this approach, the typical duration of a clinical trial in the symptomatic stages of AD has been 2 years or less; however, FDA recognizes that it may take longer to establish a clinically meaningful treatment effect in early AD due to the minimal or absent cognitive and functional deficits seen in those stages of the disease.
Additionally, many of the assessment tools typically used to measure functional
impairment in patients with later dementia stages of AD (Stages 4 through 6) would not be sensitive to detect subtle functional changes in early AD. Therefore, FDA may consider other approaches, including endpoints based on cognitive assessments or surrogate endpoints, which may allow for shorter trial durations as a basis for approval in the earliest stages of AD (i.e., Stages 1, 2, and early 3).
Cognition, in its entirety, encompassing all its constituent processes and domains, is essential for daily functioning. As previously noted, it can be challenging to interpret the clinical meaningfulness of small changes detected on sensitive neuropsychological tests; however, more marked cognitive changes may represent a change that is clearly clinically meaningful. It follows, in concept, that cognitive changes of a particular magnitude, or breadth of effects across multiple domains, or change in trajectory over time, may represent clinically meaningful change, independent of measures of functional change.
In the setting of therapy that targets underlying disease pathophysiology, changes in the long-term course of core cognitive measures of AD relative to placebo may potentially provide evidence of clinically meaningful effect with respect to the clinical progression of the disease. It would generally be expected that such effects on cognitive measures would be supported by similarly persuasive effects on the characteristic pathophysiological changes of AD.
In patients in the earliest clinical stages of AD (refer to section IV. D., Considerations for Specific Stages of Early AD), FDA will consider strong justifications that a persuasive effect, considering both magnitude of effect and statistical robustness of the findings, on cognition alone as assessed by sensitive neuropsychological tests may provide adequate support for a marketing approval. Given the array of available neuropsychological tests, a pattern of putatively beneficial effects demonstrated across multiple individual tests would increase the persuasiveness of the finding; conversely, a finding on a single test unsupported by consistent findings on other tests would be less persuasive. Whether effects on cognitive outcome measures would be capable of providing evidence of effectiveness in the absence of a meaningful change in function to support either traditional or accelerated approval would require detailed discussion with the Agency. However, in a trial with relatively short-term assessments, such as a trial for a therapy intended to treat symptoms of AD, an effect on sensitive measures of neuropsychological performance of uncertain independent clinical meaning (e.g., a word-list recall test) would generally not allow for an overall finding of efficacy in the absence of meaningful functional benefit.
Contains Nonbinding Recommendations
Draft — Not for Implementation
B.
Time-to-Event Analysis
The use of a time-to-event analysis approach (e.g., time to the occurrence of a clinically
development.
C.
Surrogate Endpoints
Clinical trials showing an effect on a surrogate endpoint that is determined to be "reasonably likely to predict clinical benefit" can be the basis for accelerated approval,' including for drugs intended for the treatment of AD. For example, in certain circumstances, FDA has considered a reduction of the brain amyloid beta burden, as assessed by positron emission tomography, to be a surrogate endpoint that is "reasonably likely to predict clinical benefit." That endpoint, in clinical trials that enrolled participants with Stage 3 and 4 AD, has thus been used as a basis for accelerated approval for monoclonal antibodies directed against aggregated forms of amyloid beta, with postapproval trials required to verify and describe clinical benefit.
The acceptability of a surrogate endpoint for use in a particular therapeutic development program for early AD may depend on the stage of disease, population enrolled in trials, therapeutic mechanism of action, and availability of current treatments. A surrogate endpoint that is determined to be appropriate for use in a particular therapeutic clinical development program should not be assumed to be appropriate for use with a different product or trial population.
Sponsors considering the use of a biomarker as the primary measure of effect should discuss their plans with FDA early in development. In general, even if accelerated approval is considered as the initial approval pathway, clinical outcome assessments should be included in clinical trials for early AD to assess early clinical changes that may potentially provide support for any changes observed on biomarkers. Evolution of the scientific understanding of AD may also influence these considerations.
FDA strongly supports and encourages continued research in understanding the role of biomarkers in AD and stresses the potential importance of biomarkers in the successful development of effective treatments appropriate for use in the earliest stages of AD.
Precompetitive structured sharing across the AD scientific community of rigorously collected standardized data is a crucial component of this research.
https://erpbiomarkers.org/
Thanks Nidan!
Powerwalker, have you heard anything from Hoskuld? He disappeared from the mb after the January 2nd Rett announcement.
I know he was heavily invested here,
Also pertains to AVXL…IMO
Smitty5150 on lhub
While NWBO and NVDA are in two very different Industry's, there are some parallel's here. I met Jensen Huang in 2017 at CES in Las Vegas.
He told me: "When you are on the right track, you will face massive resistance from virtually every angle. When you are off track, no one will attack you because you are not a threat to anyone's technology. They will just let you sink yourself".
Okay, he got that out of the way, another Rett trial will be required to move forward.
Now AD full steam ahead!
Hoping to at least get some useful nuggets from the Q&A this morning on the peer review or discussions with the regulators.
From ST-SAVXL I see the mass frustration on the boards. I understand it. The share price erosion does not align with what we've been told...that there's been a stat sig, "landmark" study, where data has been shared with at least one regulatory body, and a submission coming. We've also seen a trickle of additional, good data shared at the recent investor conferences i.e AB 42/40 marker of response blowing the socks off Biogen or Lilly). Chris was confident as hell in these last two presentations. So where is the peer-review?...and what's up with the daily lawsuit 'news', the general market turning risk-off, and now Chris selling a super tiny fraction of his shares???
This is all noise. If I ignore this noise and work from the topline data, additional data we have seen, and the people they've attracted to execute, this by all accounts remains an amazing story with unparalleled potential. I'm chosing to believe in the well documented science, versus the panicky 'fraud' nonsense.
GLTA Bullish
THANKS VELIGER from ST for this great post!
Dr. Daniel Klamer (VP, Business Development & Scientific Strategy / longtime, key member of the management team at Anavex) will be presenting at the 15th Annual Outsourcing in Clinical Trials East Coast 2024 conference on May 21st:
CASE STUDY: TARGETING ALZHEIMER'S DISEASE AND DEMENTIA IN PARKINSON'S DISEASE WITH BLARCAMESINE (ANAVEX®2-73)
Clinical efficacy is associated with biomarker expression and restoration of neurodegenerative pathways
• Blarcamesine (ANAVEX®2-73) treatment result in significant improvements in patients with Alzheimer's Disease and in Parkinson's
Disease Dementia
• Analysis demonstrates predictive biomarker of efficacy in Alzheimer's Disease and in Parkinson's Disease Dementia
• Whole blood transcriptomics analysis (RNAseq) identifies treatment impact on pathways impaired in neurodegenerative diseases
https://www.arena-international.com/event/
octeastcoast/#agenda
Outsourcing in Clinical Tri
OCT East coast
arena-international.com
THANKS Michael Tavares from the FB group!
Trulieve 2:05 from ST-
•$AVXL fda.gov/media/110903/ download has anyone seen this updated guidance from the FDA? It seems that this is HUGE NEWS! See lines 145-210 but what it looks like is that you only need one endpoint met to be cleared for approval now. For US ADAS COG does it. Didn't we do great with this endpoint? I hope we are going hard for approval right now and not waiting for EMA. How come this is not out in the mainstream?
https://www.fda.gov/media/110903/download
MayoMobile 2:11 PM
@Trulieve EMA realized that in very early patients (FDA defined as stage 1 through 3; Anavex of which enrolled primarily stage 2 and early 3) it is very difficult to assess activity of daily living improvement - because most of these patients don't have problems with ADL.
Now all you need is a strong cognitive endpoint (ADAS-COG), global endpoint for stage 3 patients (CDR-SB), and effect on underlying physiology (amyloid, tau, brain atrophy, etc).
Anavex likely to be granted
Accelerated Approval under this guidance.
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MayoMobile 2:11 PM
@Trulieve FDA****
https://www.earth.com/news/junk-proteins-responsible-for-aging-cause-als/
Anavex Life Sciences Corp.
50m • G
The accumulation of 'junk proteins' has been identified as one cause of aging.
SIGMAR1, which is activated by ANAVEX compounds, has been demonstrated to reduce the accumulation of junk proteins.
#Anavex #Dementia
#Neuroscience #junkproteins
Accumulation
NEW YORK, Feb. 26, 2024 (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 disorders including Alzheimer’s disease, Parkinson’s disease, Rett syndrome, schizophrenia and other central nervous system (CNS) diseases, today announced that it will present at the 44th Annual TD Cowen Health Care Conference, March 4-6, 2024. Christopher U Missling, PhD, President & Chief Executive Officer will present the Company in a session scheduled at 1:30 PM (ET) on Monday, March 4th, 2024, at the Boston Marriott Copley Place in Boston, MA.
A live audio webcast will be accessible through the Investors section of the Company’s website at www.anavex.com. An archived edition of the session will be available later that day.
Now that’s GREAT NEWS George!!
Schizophrenia is huge.
https://www.anavex.com/post/anavex-life-sciences-announces-phase-2-clinical-trial-anavex-3-71-schizophrenia
Sab, Dr Missling did mention something about the large turnout!
Maybe people are starting to pay attention.
Although it sure isn’t reflected in the share price.