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BigBioBoom fromST-
SAVA looks like dead junk.
Wow. once they put in a placebo. in
12 months likely.no difference
between sava and placebo.. 6
months was not statically
significant. There goes another
competitor ..
And then there is this little tidbit x3-
Kun Jin, Ph.D
Dr. Jin had a distinguished career of more than 27 years at the FDA. During his tenure at the agency, Dr. Jin has contributed extensively to statistical review issues and trial designs surrounding the regulatory approval of drugs for the treatment of neurological diseases including Alzheimer’s disease, Parkinson’s disease, migraine, epilepsy, and multiple sclerosis, as well as rare diseases, such as ALS and DMD. Dr. Jin was the lead author in top theoretical statistics, biostatistics, and molecular genetics journals. He was also a winner in a worldwide innovation competition on clinical cardiology data processing (Predicting Acute Hypotensive Episodes).
Dr. Jin has extensive research experience in Alzheimer’s clinical trials. He has been an invited speaker and has authored publications on topics in Alzheimer’s disease endpoints and trial designs. He conducted FDA/CDER The Oak Ridge Institute for Science and Education (ORISE) Summer Fellowship projects, built the Integrative Alzheimer’s Trial Database, FDA/CDER Regulatory Science and Review (RSR) Project and the results have been communicated at Accelerate Cures/Treatments for All Dementias (ACT-AD), Drug Information Association (DIA), and Joint Statistical Meetings (JSM). Before joining the FDA, Dr. Jin was Assistant Professor at the Division of Biostatistics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania. Dr. Jin received his Ph.D. in Statistics from the University of California at Berkele
Emmanuel O Fadiran, RPh, MS, PhD
Dr. Emmanuel O (“Tayo”) Fadiran, Senior Vice President of Regulatory Affairs has over 26 years of experience in government service, of which 24 years were dedicated to the Food and Drug Administration (FDA). Prior to Anavex®, Dr. Fadiran served as Clinical Pharmacology Team Leader at the Food and Drug Administration’s (FDA) Center for Drug Evaluation and Research (CDER). During his 24 years (1993-2017) tenure at the FDA he reviewed hundreds of NDAs, sNDAs, BLAs, ANDAs and INDs for approval and strategic recommendations for the development of several products across many therapeutic categories. He was also on review teams for several novel therapies including first in class approvals. Dr. Fadiran also led a cross-disciplinary NDA review team and authored the first Cross-Discipline Team Leader (CDTL) review for the Division of the Pulmonary & Allergy Products, Office of Drug Evaluation II, CDER. He was actively involved in the writing, internal/external training and the implementation of the US FDA Guidance for Industry for population pharmacokinetics.
Dr. Fadiran has been involved in the formulation of significant strategic FDA regulatory initiatives including serving as a member of the Senior Management Teams for the Data Standard (Janus) and Sentinel Initiatives. He was an active member of the FDA Senior Science Council working group for the creation and launching of the FDA’s Strategic Plan for Regulatory Science in 2012. Recently he has played an active role in the development of the Comprehensive in vitro Proarrhythmia Assay (CiPA) for future replacement of the thorough QT studies. As a long-term member of the FDA Institutional Review Board (IRB) he actively contributed to the development of standard operating procedures (SOP) for the committee.
Dr. Fadiran holds a BS (Pharmacy) and MS from Obafemi Awolowo University, Ile-Ife, Nigeria and a PhD in Pharmaceutical Sciences from the University of Strathclyde, Glasgow, UK. Dr. Fadiran is a recipient of the prestigious Fogarty International Fellowship of the National Institutes of Health (NIH) (1991-1993) as well as numerous awards from the FDA, among them the Commissioner’s Award of Excellence, in recognition of his outstanding contributions to regulatory review of applications and development of regulatory guidance and policies.
Dr. Adebayo Laniyonu PhD
Dr. Adebayo (Bayo) Laniyonu, Senior Vice President for Nonclinical Development, has over 24 years’ experience with US Food and Drug Administration (FDA).
?
Prior to joining Anavex, Dr. Laniyonu served as Supervisory Pharmacologist/Toxicologist at the FDA Center for Drug Evaluation and Research (CDER). He has reviewed hundreds of NDAs, BLAs (including first in class), sNDAs, ANDAs and INDs and provided high impact regulatory and strategic recommendations to the Sponsors of these products. He organized, chaired and presented at FDA workshops and at scientific sessions of professional societies where he presented on FDA current thinking on regulatory issues, he has also presented at FDA Advisory Committee meetings. His review and Supervisory experience span several therapeutics areas including Rare Diseases and Medical Genetics, hematology, Medical Imaging, Radiation Medicine and Medical Counter Measures products. Dr. Laniyonu played pivotal roles in the development of several FDA regulatory guidance documents.
Dr. Laniyonu holds a PhD in Pharmacology from the University of Glasgow, UK where he was a Commonwealth Scholar. He was also a Canadian Cystic Fibrosis Post-Doctoral Fellow. Dr. Laniyonu was a recipient of many FDA distinguished awards including Department of Health and Human Services Secretary’s Award for Distinguished Service, FDA Award of Merit, FDA Outstanding Service Award, FDA Group Recognition Award, CDER Excellence in Communication Award, CDER Excellence in Mentoring Award.
Not a single Missling Option post since yesterday!
Is it almost over???…the Missling option non-stop drama??
Welcome the “ second half of 2023”, hopefully the fun begins!
I can’t wait until everyone’s obsession with Missling’s options passes!!
I don’t get it. This wasn’t a surprise.
I was much more interested in the news today.
“Study Demonstrates Disease Modifying Effects of ANAVEX®2-73 “
Him and Doc wouldn’t be impressed in the drug was approved for all indications!
https://www.partex.io/our-platform/
Impressive company!
Looks like a good move.
And no, this is not the BP partnership replacement, that will come after approval per Dr Missling’
From excellent poster on ST- 100fold 1m
SAVXL I listened to the call and my
reflections follow:
-The call covered 4 main topics: AD,
PD,RETT, financials, partnerships
-Confirmed that the company is
excited about taking the AA approach
to approval, where they have the
same or better bio marker
improvement that the approved
MAB's have. Indicated that
Lecanemab trial screened out 80% of
AD population, and they included
80% of all trial applicants. Nothing
on timing of full data.
-Confirmed PD trial will be pivotal
and start this year. Excited about
results from
"drug holiday' to see
patients discontinue and worsen and
then continue and improve.
Longest discussion was about Rett.I
sense from CM that they will go for
the voucher and expect
To get $80 - $100 MM on its sale. This
means RETT approval before AD. He
said if the Excellence trial has good
results the drug will be approved.
Strategy was to follow Trofinetide, an
inferior indication, to market to
establish pricing ($500,000) and
insurance procedure codes.
Interesting ST posts- plotdog 9:34 AM
$AVXL Key Near Term
Pipeline Updates:
• Alzheimer's disease: Full data
ANAVEX®2-73-AD-004, including
newly available preliminary results of
surrogate biomarkers of pivotal
Phase 2b/3 clinical trial. The
Company intends to discuss these
findings with regulatory authorities
in the context of the ongoing clinical
development of ANAVEX®2-73 in this
indication, with the goal of providing
a much-needed treatment to the
millions of patients living with
Alzheimer's disease with a
convenient once-daily oral
treatment. The Company plans to
proceed in parallel with the initiation
of a confirmatory Alzheimer's disease
study.
This possibly could have the
potential to completely change how
science and medicine looks at
Alzheimer's disease. Exciting stuff.
100fold 52m
@plotdog This might explain the
delay in the PD and Fragile X trial
initiation. The FDA may have
recommended they go for AA to
provide cover for the similar
approvals of the MAB's, rather than
cut a new path to gain traditional
approval on what many consider
subjective endpoints, even though I
believe they not only met endpoints,
but the data will be robust in its
improvement of patient quality of
life. By going the AA route, they
would need to initiate a confirmatory
trial per AA protocol. So all hands on
deck for AD trial? And all hands on
deck for RETT approval. That's my
guess.
I am expecting excellent results from the Rett trial in a couple months leading to an NDA and approval.
Having an already approved drug on the market will definitely help with the AD approval process.
Also, there is the Dr Jin factor. Jin just recently retired from the agency where he was very well respected and still has strong connections.
Some here may disagree, but I know how things work in the real world. Sometimes, it’s not what you know/have, it’s who you know!
I believe Dr Jin is having off the record talks with his former colleagues about the drug and how to get it approved.
The feds desperately need a win after the last couple of failures!
Factanonverba from the stockwits message board first posted it.
Coming from the Alzheimer’s Association, I think it’s significant, as they have somewhat shunned Anavex until now.
Is this considered a “peer reviewed “article ?
https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.059024
Coming from the Alzheimer’s Association is a big step forward IMO!
Anavex's Blarcamesine: Sigma-1 Receptor Agonists And Antioxidants For Alzheimer's Disease
Jun. 06, 2023 9:00 PM ETAnavex Life Sciences Corp. (AVXL)11 Comments
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Lane Simonian
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Summary
Blarcamesine, a sigma-1 receptor agonist, may be a more effective antioxidant than Aricept and galantamine in treating Alzheimer's disease.
If granted accelerated approval by the FDA, Anavex's stock value is expected to rise significantly.
Anavex may provide the best investment opportunity and drug hope for the near long-term stabilization of mild Alzheimer's disease in those with functioning sigma-1 receptors.
Woman contemplating nature of Sweden relaxing on moss in the forest
Anastasiia Shavshyna/E+ via Getty Images
Sig-1R agonists would be ideal drug candidates for translational medicine, because the known ligands have limited side effects: their modulatory action starts only under pathological conditions… [However] Application of Sig-1R agonists alone, very probably, will not be sufficient for the treatment of neurodegenerative diseases (source of quote).
The inflammatory mediator peroxynitrite, when generated in excess, may damage cells by oxidizing and nitrating cellular components. Defense against this reactive species may be at the level of prevention of the formation of peroxynitrite, at the level of interception, or at the level of repair of damage caused by peroxynitrite (source of quote).
I have compared the effects of the sigma-1 receptor agonists Anavex’s (NASDAQ:AVXL) 2-73/ blarcamesine and Aricept/donepezil in a previous article (and most recent article). In this article, I will also compare blarcamesine with another (likely) sigma-1 receptor agonist: the isoquinoline alkaloid galantamine. The comparison should clarify the combined role that sigma-1 receptors and direct antioxidants play in the treatment of Alzheimer’s disease.
Blarcamesine may be a better antioxidant than Aricept and galantamine which may explain why it helps nearly stabilize early stage Alzheimer's disease over longer periods of time. If granted accelerated approval by the FDA (allowing the drug to be sold while a confirmatory trial is run), AVXL stock value should rise considerably.
Sigma-1 Receptor Agonists in the Treatment of Alzheimer's Disease
As sigma-1 receptor agonists, Anavex’s blarcamesine, Aricept, and galantamine limit the formation of peroxynitrite. Blarcamesine, Aricept, and galantamine may also scavenge oxidants (such as peroxynitrite), but the evidence for this is inconclusive at this point. Aricept may not be an effective antioxidant at therapeutic doses. The antioxidant effects of galantamine may be partially offset by its activation of NMDA receptors. The evidence that blarcamesine is an antioxidant is largely indirect. More studies on the potential antioxidant capacities of each is needed.
Sigma-1 receptor agonists on their own slow down mild Alzheimer’s disease for about a year. The following results once adjusted for different baselines are nearly identical (the expected placebo decline from a Mini-Mental State Examination score of 21 is around 2.3 points at one year).
Galantamine (280 patients at one year)
23.17 to 22.98
Aricept/donepezil (492 patients at one year)
22 to 21
Anavex 2-73/blarcamesine (at the highest dose: 9 patients at 57 weeks; approximate calculation)
21 to 19.3
Sigma-1 receptor agonists are less effective or ineffective in those with deficits in sigma-1 receptors (either low levels or low activity). They only slow down the progression of mild Alzheimer’s disease. And they have almost no effect on moderate to severe Alzheimer’s disease (as will be discussed later).
In regards to the second point, sigma-1 receptor agonists do not completely stop the release of intracellular calcium which contributes to oxidative stress and they do not inhibit the production of diacylglycerol which also contributes to oxidative stress (see chart below).
Inositol Triphosphate Pathway
Pathway in Early Alzheimer's Disease (Science Signalling)
GPCR: G Protein-Coupled Receptor
rTK: receptor Tyrosine Kinase
PLC: Phospholipase C
PIP2: Phosphatidylinositol 4,5 Bisphosphate
IP3: Inositol 1,4,5 triphosphate
ER: Endoplasmic Reticulum
Ca+2: Calcium Ion
DAG: Diacylyglycerol
Sigma-1 Receptor Agonists and Antioxidants
For mild Alzheimer’s disease, a sigma-1 receptor agonist must also be a strong antioxidant or combined with a strong antioxidant to stabilize or nearly stabilize the disease over longer periods of time. The stronger the antioxidant the better the results. Blarcamesine and panax ginseng for instance, may help reduce and reverse oxidative and nitrostative stress via the scavenging of hydrogen peroxide (early in the disease) and peroxynitrite. Blarcamesine is a tetrahydrofuran derivative and tetrahydrofurans appear to be excellent hydrogen and electron donors, which is what is needed to accomplish the above. De-nitration and/or the reversal of oxidation leads to an increase in critical neurotransmitters in Alzheimer’s disease (including those needed for the accessing of short-term memory, sleep, alertness, social recognition, and balanced mood), the partial regeneration of neurons, and the reduced death of neurons.
Three year studies appear to confirm the value of the sigma-1 receptor agonist/antioxidant approach to the treatment of mild Alzheimer’s disease. One should note that there was a high dropout rate in the galantamine and donepezil studies which may have reduced the number of participants with sigma-1 receptor variants and very few individuals with a sigma-1 receptor variants completed the Anavex phase 2a trial, so the results in the general population may not be as good.
For patients with mild cognitive impairment and mild Alzheimer’s disease and who did not have sigma-1 receptor and catechol-o-methyltransferase gene variants, blarcamesine at the highest concentration produced a 2 point improvement in MMSE scores at 57 weeks and a three point improvement in MMSE scores at 70 weeks. In eight patients at high concentrations (most, but not all of whom, fit the description above) the decline was about 1 point at 148 weeks (from a baseline of around 21). In the case of Aricept the decline in MMSE scores at three years was 3.8 points (from a baseline of 22). For galantamine, the decline in MMSE scores at three years was 2.6 points (from a baseline of 23.17).
By combining the functions of a sigma-1 receptor agonist and a peroxynitrite scavenger, blarcamesine appears to nearly stabilize mild Alzheimer’s disease for at least 148 weeks in those who having a functioning sigma-1 receptor.
By comparison, panax ginseng which inhibits phospholipase C activity and is a peroxynitrite scavenger, produced a 2.6 point improvement (21.4 to 24) at the higher dose in those with mild Alzheimer’s disease at 96 weeks (clinical trial). Importantly this improvement occurred regardless of sigma-1 gene status.
For Moderate to Severe Alzheimer's Disease
Sigma-1 receptors have little to no effect on moderate to severe Alzheimer’s disease because some of the receptors and enzymes involved in the onset and initial progression of Alzheimer’s disease become damaged by oxidation and nitration. The nitration of protein kinase C, for instance, largely abrogates the effects of sigma-1 receptor agonists on moderate to severe Alzheimer’s disease. Despite the inactivation of protein kinase C, the NMDA receptor remains over-activated for some time at least due to high levels of glutamate (caused by the peroxynitrite-mediated disabling of glutamate transporters).
Glutamate Excitotoxicity
Alzheimer's Disease Pathways (Frontiers in Cellular Neuroscience)
Key acronyms
PKC: Protein Kinase C
mGluR: metabotropic Glutamate Receptor (a g-protein coupled receptor)
NMDAR: N-Methyl-D-Asparate Receptor (an ionotropic glutamate receptor)
ONOO-: peroxynitrite
GSH: Glutathione
Ginseng may help improve glutamate transport. It may also inhibit peroxynitrite formation after NMDA overactivation via inhibition of nuclear factor kappa B as well as scavenge peroxynitrite. In part due to these actions, panax ginseng may stabilize moderate Alzheimer’s disease for at least a year.
Chinese herbs and Alzheimer's Disease
Herbs plus Conventional Therapy for the Treatment of Alzheimer's Disease (BMC Complementary and Alternative Medicine)
Alzheimer’s disease is like a stopped sink. If you turn down the tap you slow down the filling up of the sink, but if you turn down the tap and remove some of the water, you can stabilize the water levels in the sink. Early in Alzheimer’s disease and in those with the “right” genetic makeup, sigma-1 receptor agonists inhibit oxidative and nitrostative stress, neuroinflammation, mitochondrial dysfunction, synaptic dysfunction, and the death of neurons (i.e. they turn down the tap), but they can only stop or nearly stop the progression of the disease when combined with compounds that also scavenge and reverse part of the damage done by peroxynitrite (i.e. bail out the water). Blarcamesine may come closer to achieving this objective than Aricept and galantamine, because it may be a more effective antioxidant than either. By working further upstream and downstream than blarcamesine, panax ginseng may help those without a functioning sigma-1 receptor and those with moderate Alzheimer’s disease for a while at least.
If the 50mg group numbers in Anavex’s phase 2b/3 clinical trials match those of the high concentration numbers in its phase 2a trial, then the FDA is likely to grant accelerated approval for blarcamesine for mild Alzheimer’s disease in individuals who have functioning sigma-1 receptors. An accelerated approval would allow Anavex to sell blarcamesine while it runs a confirmatory phase 4 clinical trial. Even taking into account the skepticism that has followed overall positive results in the past, Anavex’s stock value should rise quite significantly following such a decision. If however, Anavex has to run a larger (and perhaps longer) phase 3 clinical trial to gain the FDA’s approval that would seriously hurt the company’s stock value (although it currently has the resources to complete such a trial). FDA approval of an Anavex compound for another neurological condition (such as pediatric Rett syndrome) would soften the blow a little bit.
In conclusion, despite their slow release of data, Anavex may provide the best investment opportunity and the best drug hope to date for the near long-term stabilization of mild Alzheimer’s disease in those with functioning sigma-1 receptors.
Any thoughts on this?
Annelise's Army
20h • G
Annelise's dad is currently in Nashville
representing the Rett Syndrome Association of
Australia at the IRSF Rett Syndrome Scientific
meeting. What a buzz it will be there today with
the news released a few hours ago that an
adult with Rett Syndrome had been the first
patient to be given the first dose of Gene
Therapy as part 1/2 investigation trial.
Thank you patient number one.
ir.tayshagtx.com
Also , this was clearly stated- “In communication with the FDA, the Company received the Agency’s input on the study endpoints, which were utilized in this clinical study. “
Looks like they finally learned from the past!
Anavex is a silver sponsor however!
https://www.rettsyndrome.org/2023scientificmtg/
Biogen, Denali to halt late-
stage trial for Parkinson's
disease drug
Jun. 05, 2023 10:26 AM ET | Denali Therapeutics Inc.
(DNLI), BIIB By: Dulan Lokuwithana, SA News Editor
Parkinson's Disease
Denali Therapeutics (NASDAQ:DNLI)
announced Monday that the company and
its partner Biogen (NASDAQ:BIIB) have
decided to discontinue a Phase 3 trial for
Parkinson's disease (PD) candidate BIIB122
(DNL151).
The company said the decision follows a
review of its portfolio timelines and existing concerns related to BIIB122.
In line with a collaboration, Denali (DNLI)
and Biogen (BIB) were advancing BIlB122 in
two global late-stage clinical trials: Phase
2b LUMA study targeted at early-stage PD
and Phase 3 LIGHTHOUSE study for PD-
related to LRRK2 mutations.
The companies said that patients already
enrolled in the LIGHTHOUSE trial could join
the LUMA study, which, as part of the
review, has also been modified to include
PD patients with LRRK2 mutations.
Interesting post fromMinnesotastockdude on ST
$AVXL Imo, it is clear Missing is
waiting to release the full data in a
detailed scientific publication, that
covers ten years of clinical results
Including:
Alzheimer's p2a + extension
Alzheimer's p2b/3
Parkinson's p2 + extension
Genomic sequencing
mRNA analysis showing correlation
between the MoA and patient's
Sigmar 1 receptor
A variety of other data (e.g gut
microbiome)
I'm not saying missling's
communication and speed isn't
frustrating
I am saying that after 10 years of
meticulous moves, it makes sens
wait to release the full data in a
published paper
Detailed published papers take
longer to be produced and released
than the analyzation of data itself
After a 10 year wait, a few more
months is well worth it to ensure the
publication and application is
bulletproof. Imo
For David, I also think it's highly
beneficial that our application will
come after Goliath was corruptly
approved. The bar is clearly set and
missing can show exactly how their
results beat it Bullish
Sorry VG, I didn’t see that you already posted the article.
Thanks George, looks like they they are building a pretty solid IP protection.
I remember a couple years ago, this was a popular topic for the “FUDSTERS “
Proven wrong once again and more to come.
Dr Missling has his issues, but the man is no dummy.
He has surrounded himself with a very experienced and capable team.
I’ll say it again, recruiting Dr Jin was one of his best moves for many reasons.
Energy independence
Kun Jin, Ph.D
Dr. Jin had a distinguished career of more than 27 years at the FDA. During his tenure at the agency, Dr. Jin has contributed extensively to statistical review issues and trial designs surrounding the regulatory approval of drugs for the treatment of neurological diseases including Alzheimer’s disease, Parkinson’s disease, migraine, epilepsy, and multiple sclerosis, as well as rare diseases, such as ALS and DMD. Dr. Jin was the lead author in top theoretical statistics, biostatistics, and molecular genetics journals. He was also a winner in a worldwide innovation competition on clinical cardiology data processing (Predicting Acute Hypotensive Episodes).
Dr. Jin has extensive research experience in Alzheimer’s clinical trials. He has been an invited speaker and has authored publications on topics in Alzheimer’s disease endpoints and trial designs. He conducted FDA/CDER The Oak Ridge Institute for Science and Education (ORISE) Summer Fellowship projects, built the Integrative Alzheimer’s Trial Database, FDA/CDER Regulatory Science and Review (RSR) Project and the results have been communicated at Accelerate Cures/Treatments for All Dementias (ACT-AD), Drug Information Association (DIA), and Joint Statistical Meetings (JSM). Before joining the FDA, Dr. Jin was Assistant Professor at the Division of Biostatistics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania. Dr. Jin received his Ph.D. in Statistics from the University of California at Berkeley, California.
Are there any restrictions placed on a drug that has received AA? Is the marketing and sales given full authorization as if it is fully approved?
If approved ,can Anavex and it’s partner sell the drug off label for other indications?
If after a few months into the confirmation trial and overwhelming efficacy is being reported, can the trial be halted early and given full approval?
TIA
HB
“Dr. M.did note that the 30 mg performed almost as well as the 50 mg in the improved group. “ -From Powerwalkers notes
I would like to hear thoughts about this!
Is this a positive or negative?
I thought that everyone was assuming that the 50 mg group would have blowout results when separated from the 30mg group.
Thanks so much Hoskuld, Bourbon and Power walker for your SHM reports!
It all sounds pretty encouraging, just a few more weeks/months of patients.
Powerwalker, thanks for the updates, I, and I’m sure the rest of the longs here , would really appreciate any nuggets of information that you or any one else that attended can give to us!
Thanks again
Pitch forks and torches today as some one posted a couple weeks ago?
Kind of odd that there are no premarket trades.
We have all seen this movie many times before. I’ll leave it at that.
Who knows, maybe we will get a surprise PR before the meeting
What kind of PE could we expect with that type of revenue? 15?, 20?
Did you happen to notice my post started off with “IMO” mr. scoreman?
Did you take what I posted as facts as to what was for sure happening to require links?
Maybe in your mind only verifiable facts are to be posted with no opinions or possibilities welcome?
IMO, the reason Anavex is keeping the the AD data so close to the vest is that they are in talks with the TGA, EMA and the FDA about getting approvals,
For that matter, I’m sure that they are in talks with several BP’s for partnering.
Letting the cat out of the bag now to the whole world would just complicate the ongoing discussions.
Although sometimes difficult, I am trying to be patient and trust the Anavex is making the right moves to get the drug on the market.
Repost of Tom Bishops comments-
Tom Bishop talked to Anavex post CC. Here are his comments.
Anavex’s (AVXL $9.20, +9%) (… and wow, Aris is up 25% this morning, I’ll hit that next!) quarterly release and conference call was this morning. And after speaking with the Company and clarifying a few issues, there were some exciting revelations. First and foremost, the Company now believes, after 5 months of evaluating the data, that the data from the resent Phase 2b/3 Alzheimer’s trial, and especially the data from the improvement in surrogate biomarkers that are associated with the pathology of Alzheimer’s are strong enough that it intends to apply to the FDA for approval of A2-73 based on the “Accelerated Approval Pathway.” Now this doesn’t just mean the process moves along more quickly while it now does a full phase 3 trial. This means conditional approval for commercial sale of A2-73 based on the data already collected from the Phase 2b/3 trial, especially that based on improvement in the various Alzheimer’s disease pathology biomarkers, along with the cognitive and other improvements in functional data itself. And then a confirmatory study would be done while the drug is already approved. Recent Alzheimer’s drug approvals (Biogen and Lilly) have all utilized this pathway and evidence of improvement of various biomarkers for Alzheimer’s disease. So this is rather exciting as there is a reasonable chance now that the Company could get approval relatively soon without waiting to first conduct a full blown Phase 3 trial. No guarantees on this, but very encouraging re the potential time line to market acceleration. Here is something more on this pathway–
“The pathway specifically allows FDA to approve drugs based on a determination that the product has an effect on certain surrogate endpoints or intermediate clinical endpoints. Surrogate or intermediate endpoint can be based on a laboratory measurement (like blood glucose level for diabetes), radiographic image (like tumor size reduction), physical sign (like blood pressure for cardiovascular disease) or other measure. For instance, reduction of viral load in HIV patients, reduced tumor size in cancer patients or alleviation of symptoms can all be used to show a treatment’s benefit to patients. Congress has clarified, through statute, that the accelerated approval pathway does not alter the standards of evidence required for approval.
After a medicine is granted accelerated approval, companies are required to conduct, and provide updates on, confirmatory trials and the FDA is required to make this information publicly available.
Companies are required to conduct confirmatory studies of medicines granted accelerated approval and are subject to reporting requirements on the status of these studies. The FDA is required to track, and make publicly available, progress of confirmatory trials.”
Remember that the safety data is much better than those Alzheimer’s drugs recently approved that can cause brain swelling/bleeding (maybe even death) and the need for periodic/expensive MRI’s to monitor this. AND A2-73 is an oral formulation not infusion therapy. So all things being equal, what are you gonna take?
Now the other cool thing here is, as announced in a press release last week, the Company has filed for a patent covering A2-73’s use to lower high blood pressure. As you might expect, when patients came in for periodic trial evaluations, they got their blood pressure taken. And the Company noticed that those coming in with high blood pressure saw that drop back into the normal range! So while the Company is a ways off from pursuing this indication on its own, if it can claim this side benefit, in addition to the Alzheimer’s benefits above … like I said, which one are you gonna choose? Duh. (I also recall some potential benefits regarding improved sleep, I hope we get data on that also.) It’s like how they have discovered lately that some of the diabetes drugs (Eli Lilly’s in particular)) cause significant weight loss! So now these diabetes drugs are in short supply because other people are taking them just for weight loss. So A2-73, if approved, could then potentially be prescribed off label for blood pressure, or at least more likely advertised as a side benefit. The blood pressure data has not been disclosed but perhaps will be in the full release in a medical journal that will cover all the things we have been waiting for (30 vs. 50 mg, ADL and COG, sigma1 normal gene vs. the variant, all the other biomarker data … ).
Elsewhere, I believe they are at last getting very close to announcing the Phase 3 Parkinson’s disease trial initiation, in addition to the full A2-73 data release, plus in H2 the Rett Pediatric data. While this seems to move very slowly the Company is meticulous in its approach, avoiding the pitfalls so many companies fall into with their failed clinical trials and I would remind everybody once again that they have never failed one of their clinical trials. They have all been successful in showing efficacy, and that consistency itself tells you something. Small wonder Dr. Missling reiterated in closing that “… looking forward we’re very excited about the Company’s potential as well as to build the bio-marker driven precision medicine studies…”
There was more meat on the bone than today’s stock market reaction gives credit for (it was down in the pre-market but I see as I finish this that it is now up 8%, still … plenty of room ahead)- Buy.
Thanks Booka!
If a PH3 is to be ran with AA, does the trial have to be recruited and fully running to market the drug? Or can the drug be sold during the planning/recruiting?
If a PH3 is to be ran with AA, does the trial have to be recruited and fully running to market the drug? Or can the drug be sold during the planning/recruitment phase?
If Anavex is getting a strong signal that they will get AA for AD, will they still holdout for the RETT voucher or just go ahead with the AD approval?
I would forfeit the 100 mil voucher if it means AD approval.