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Nope... just a long time AVXL shareholder. Cut/paste error, sorry.
Plex,
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The Political Economist
I am the impassioned pundit at whyistherestillhunger.com. I have long studied and written about hunger, as...
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Approval For Anavex's Blarcamesine Looks Inevitable After Biogen's Leqembi Approved
Jan. 30, 2023 12:13 PM ETAnavex Life Sciences Corp. (AVXL)BIIB, LLY128 Comments
Sometimes my burdens and sorrows become too overwhelming to bear...
Cecilie_Arcurs/E+ via Getty Images
Based on Phase 2 data alone, the FDA has granted emergency approval to the Biogen/Eisai (BIIB) Alzheimer's drug, Lecanemab. As summed up by the prestigious science journal Nature:
The FDA’s decision does not take the phase III study into account — Biogen and Eisai asked for accelerated approval on the basis of phase II data, which they submitted before the latest trial results were announced. The phase II study found that lecanemab decreased plaques in the brains of 856 patients, but did not assess whether this affected patients’ cognitive abilities. This is the same pathway used to approve its predecessor, aducanumab, a similar antibody also made by Biogen and Eisai.
The FDA trumpeted the drug, now christened Leqembi, in its press release:
Leqembi is the second of a new category of medications approved for Alzheimer’s disease that target the fundamental pathophysiology of the disease. These medications represent an important advancement in the ongoing fight to effectively treat Alzheimer’s disease.
Did the FDA just say that Leqembi is disease-modifying? Read the next paragraph in the FDA press release of January 6th:
“Alzheimer’s disease immeasurably incapacitates the lives of those who suffer from it and has devastating effects on their loved ones,” said Billy Dunn, M.D., director of the Office of Neuroscience in the FDA’s Center for Drug Evaluation and Research. “This treatment option is the latest therapy to target and affect the underlying disease process of Alzheimer’s, instead of only treating the symptoms of the disease.”
Amyloid-clearer versus Sigmar1 agonist
The FDA declared that excess amyloid is part of the "underlying disease process." The logic is that excess amyloid is part of the cause of the disease; Leqembi reduces the amyloid in the brain (which also causes brain bleeding in some people); therefore Leqembi is disease-modifying, and should be approved on its ability to clear amyloid alone.
Thing is, many neurologists now see amyloid build-up as a symptom and not the cause of Alzheimer's disease, even as Leqembi, a drug that targets amyloid, seems to be effective.
The relevance of the Aß [amyloid] cascade hypothesis to the development of therapeutics for AD [Alzheimer's disease] appears disproven. Drugs targeting tau appear to be suffering the same fate but may yet produce better results. Alternative approaches are being pursued, some of them with initial small-scale, but promising, results.
One important new understanding of Alzheimer's is that the root cause of the disease is the malfunction in autophagy, the body's own self-maintenance system.
Anavex Life Sciences' drug, Blarcamesine, apparently spurs the autophagy systems by manipulating Sigmar1 genes and gene receptors; it appears to be more effective than the amyloid-clearing drugs, according to drug trials.
A groundbreaking, earlier study using Blarcamesine (Anavex2-73) as a Sigmar1-agonist (Sig-1R agonist) found the following:
Taken together, the in vitro and in vivo data so far clearly show that the Sig-1R agonist ANAVEX2-73 [Blarcamesine] induces autophagy, as indicated by autophagic flux measurements.
The study was completed by independent scientists and funded by German research foundations. Researchers focused also on how Sig1-R activation increased autophagic activity, which in turn would help the brain to maintain the correct levels of various chemicals:
Taken together, in both independent cell assays and in two different human cell lines, Sig-1R activation induced a significantly increased autophagic flux.
The study utilized both human tissue (in vitro) and live nematode worms injected with human tissue (in vivo):
Excitingly, ANAVEX2-73 is a potent inducer of autophagic flux in vitro and in vivo and ameliorates protein aggregate formation and paralysis in C. elegans.
For those who wonder exactly what "autophagic flux" encompasses:
autophagic flux refers to the whole process of autophagy, including autophagosome formation, maturation, fusion with lysosomes, subsequent breakdown and the release of macromolecules back into the cytosol...
In a journal publication in 2021, scientists who have been focusing on Sigmar1 as an activator of autophagy declared in their abstract that
Autophagy activation by the s-1Rs [Sigmar1's] along with other neuroprotective effects makes it an interesting target for the treatment of Alzheimer's disease. AF710B, T-817 MA, and ANAVEX2-73 [Blarcamesine] are some of the s-1R agonists which have shown promising results and have entered clinical trials. These molecules have also been found to induce autophagy and show cytoprotective effects in cellular models.
Upon publication of this important research, Anavex published a press release with two matter-of-fact bullet points:
SIGMAR1 is activated by ANAVEX-compounds
ANAVEX®2-73 has been shown to induce autophagy
Anavex Life Sciences is clearly making the case that Blarcamesine manipulates a specific biomarker (Sigmar1), and that that biomarker modifies the function of autophagy, which is at the heart of neurdegenerative diseases such as dementia and Alzheimer's. This sets up Blarcamesine for an emergency approval by the FDA based on Phase 2b/3 data demonstrating disease-modifying changes in a crucial biomarker, just like Leqembi.
New Efficacy News
The Blarcamesine Phase 2b/3 results are more impressive than the Leqembi Phase 3 results. The cognitive test results clearly favor Blarcamesine.
Blarcamesine reduced cognitive decline by 45% as measured by the ADAS-Cog, performing 40% better than Leqembi, and it did so in 11 months instead of 18 months. For a much more detailed comparison see my previous article.
New news: on a January 12 presentation at the J.P. Morgan Healthcare Conference, Anavex CEO Christopher Missling doubled down on the fact that Anavex's Blarcamesine is more effective and safer than Biogen's Leqembi.
This time, CEO Missling focused entirely on the reduction in cognitive and functional decline as measured by the CDR-SB. Both Blarcamesine and Leqembi succeeded in slowing decline by 27%, but Blarcamesine did so in 48 weeks and Leqembi took 78 weeks.
A never-before-seen graph was presented, showing the CDR-SB scores of the patients in the Blarcamesine Phase 2b/3 trial. We can see on this graph the decline in the cognitive/behavioral function of both the placebo group and the group who took the drug. After 24 weeks, the level of cognitive decline is about even. By 36 weeks, those taking Blarcamesine enjoy less cognitive decline than the placebo group, and by week 48 the lead held by the Blarcamesine group has widened considerably.
In fact, by Week 48, the worst score among the Blarcamesine group is better than the best score among those taking the placebo, according to this graph. Zero overlap. Every single one of those taking Blarcamesine was performing better than every single person taking the placebo.
Will the FDA grant approval of Anavex's Blarcamesine?
If the FDA was willing to grant emergency approval to Leqembi based solely on what it does in altering levels of a biomarker (amyloid), it seems certain that the FDA will grant emergency approval and/or ultimate approval to a drug that is more effective, likely far cheaper, and certainly safer.
First, will Anavex request emergency approval? I believe it will request emergency approval, as it called its trial a Phase 2b/3 trial. If it was not interested in approval using data from this trial, it would not have labeled the trial Phase 2b/3.
Second, will the FDA require evidence of substantial changes in biomarkers in addition to clinical data? Not sure. Blarcamesine has demonstrated significant biomarker changes in its previous trials, and Anavex will reveal the biomarker data for the Phase 2b/3 trial in the coming weeks or months.
Third, will Medicare pay for Blarcamesine if it is given emergency approval? Yes, I believe so. The drug appears to be more effective than any drug ever developed. And it is far safer than any of the Biogen drugs recently approved.
In contrast, Leqembi is an amyloid-clearing drug and often swells and bleeds the brains of patients; Medicare will not pay for Leqembi until it has full approval by the FDA. Because Anavex's Blarcamesine is not an amyloid-clearer this policy does not apply to it.
Therefore, Medicare can approve of Blarcamesine based solely on an emergency approval by the FDA.
It is conceivable that Blarcamesine could reach the Medicare constituency before Leqembi, even if Leqembi is ultimately approved by Medicare.
The Biogen Investigation and Extension Study
During, or soon after, a 6-week open-label extension study on Leqembi, three patients taking Leqembi died. Two of the deaths were directly attributed to use of Leqembi; see my previous articles for details. Six weeks is not a long time for three out of some hundreds of patients to die in a study.
The FDA has not examined Leqembi's Phase 3 data, nor has it examined data from its extension study. Biogen/Eisai claims that the deaths were unrelated to use of Leqembi, but skeptical parties like ICER do tend to get involved in analyzing situations like this.
After Congressional investigation found FDA misconduct in the approval of Biogen's previous Alzheimer's drug, Aduhelm, the FDA will certainly try to avoid a similar situation. Nature did not pull any punches in its succinct assessment:
Many researchers thought that aducanumab, which also goes by the brand name Aduhelm, did not show a strong signal of cognitive decline. The FDA’s own scientific advisory panel recommended against approving the antibody in an 8–1 vote, and three panel members resigned after the FDA authorized it anyway. The FDA did not hold a public advisory meeting for lecanemab [Leqembi] before approving it.
I imagine that there will be public hearings before Leqembi (Lecanemab) can be ultimately approved, especially after the details of the three deaths are finally examined. In fact, one family seems determined to make public the assertion that their loved one was killed by use of Leqembi.
The use of blood-thinning drugs may have contributed to the three deaths, but nothing is clear as of this point. A long investigation and public discussion may delay the drug for months. The FDA met with Biogen on 115 occasions in order to get Aduhelm approved, and many of those meetings were not documented. This time, everything will have to be above-board, and that takes time.
The need to avoid the appearance of impropriety and the patient deaths makes it more likely that Leqembi is not granted final approval, or that it may be severely delayed.
The Blarcamesine Extension Studies
The Phase 2b/3 trial ended after Week 48, but participants were given the option of continuing on in an extension study of Blarcamesine.
It will be exciting to see whether the slope for the Blarcamesine-takers remains the same in Weeks 60 and 72 and 84. If so, the reduction in cognitive decline will be far greater than that achieved by Leqembi in 78 weeks.
Examining the slopes on the graph, it is likely that by the time Week 78 rolls around, those who have been taking Blarcamesine all along will have achieved a 50% reduction in cognitive decline. In that case, Blarcamesine would have achieved a reduction in cognitive decline approaching twice that of Leqembi in the same time frame.
When comparing their extension studies, Blarcamesine will almost certainly perform better than Leqembi in the area of safety. The side effects for Blarcamesine do not include brain bleeding, brain swelling, or death; they include dizziness and confusion in some users, which might be resolved by taking the drug before bed rather than in the morning, as required by the trial.
Also, Blarcamesine's Phase 2a extension study went on for over 200 weeks, and there were no terrible side effects associated with the drug. The number of participants was very small though.
Considering the approvals of both Aduhelm and Leqembi, the FDA should approve Blarcamesine based on its greater effectiveness, safety, and lower price. Medicare may reject Leqembi and approve of Blarcamesine based solely on the extreme expense of Leqembi compared to Blarcamesine. Conceivably, Leqembi may cost tens of billions of dollars a year to purchase, administer and deal with side effects like brain bleeding. Blarcamesine may only be in the billions.
Analyst Opinions and the "High Dose" of Blarcamesine
Since last I wrote, HC Wainwright slapped a $50 price target on AVXL stock; the stock is valued at about $10 at the time of this writing. I could not find any published opinion associated with the price target.
Investor Alex Carchidi published a headline on Dec. 17 declaring that AVXL could multiply its value by 5X by 2025! But they warn that "the biotech [company] will first need to assuage the concerns of experts by elaborating on its latest clinical trial data."
During the January 12 presentation, CEO Missling said that the next step is to publish the data and its analysis in a peer-reviewed journal and to meet with the FDA to see what they think.
The most sophisticated recent analysis came from Tom Bishop of the small firm, BI Research. Bishop reminded Forbes readers in January that while the Phase 2a data showed that Anavex at 50 mg performed considerably better than the 30 mg dose, the data available so far from the Phase 2b/3 trial combines the two groups into one data set. Bishop writes:
While the data already released was superior to Lecanemab [Leqembi], once the 50 mg alone cohort data comes out the results should be considerably better than the combined group.
Indeed the previous Alzheimer's studies conducted with Blarcamesine showed a major difference between the effect of the lower doses and the higher doses of Blarcamesine. SA writer and Anavex expert Lane Simonian has written on this extensively, and he tells readers that those in the highest dose showed a 3 point IMPROVEMENT in their MMSE scores after week 70! The number of patients taking the high dose in the extension study was 4, but that is still a stunning result; after 70 weeks, Alzheimer's patients typically suffer a substantial downslide in cognitive ability.
The same was found in the Phase 2, placebo-controlled Blarcamesine trials for Parkinson's Disease Dementia (PDD); patients taking the higher dose were much more likely to actually IMPROVE in their memory, cognition, and behavior.
Both of these trends toward actual improvement is likely why Anavex doubled down on a certain type of measure that has been looked down upon by critics. That measure is the increased probability that the patient actually improves. Why does Anavex insist on repeating that the 30 mg and the 50 mg dose-takers pooled together have a 167% greater chance of improving compared to placebo, when measured on the ADCS-ADL? STAT writer Adam Feuerstein and other writers were certainly not impressed by this finding.
I believe Anavex focuses on actual improvement rather than "reduction in decline" to prepare us for the even more impressive "improvement" numbers to be released when we see the data for the 50 mg dose group. I believe we will likely see an even greater probability of clinical improvement than we saw for the combined group. What would the public think if they saw that they have triple the probability of getting better by taking the 50 mg dose of Blarcamesine?
Most of those who took the high dose in their Alzheimer's 2a (not the recent 2b/3) trial demonstrated improvement in their mental measurements.
Now, let's look at the patients in the Parkinson's Dementia placebo controlled Phase 2 trial. The vast majority of those in the 50 mg group of the PDD Phase 2 trial demonstrated actual improvement in the "episodic memory" measure, which includes "events and names". Most of the placebo got worse, and the 30 mg group was about half-half. Each of the three groups had 44 participants, so that includes 88 drug-takers in total.
In a press release in June 2021, describing further analysis of the Parkinson's Dementia Phase 2 trial, Anavex stated
ANAVEX®2-73 high dose demonstrated statistically significant improvements compared to placebo (ITT population) for MDS-UPDRS Total score (p = 0.034). From baseline to end of trial at 14 weeks, MDS-UPDRS Total score improved by -10.98 points in the ANAVEX®2-73 high dose group and worsened by 3.53 points in the placebo group, an adjusted mean difference of -14.51 points (p = 0.034). This corresponds to a relative improvement of 18.9 % over 14 weeks.
Not only is there a difference between the 30 and the 50 mg doses in effectiveness, the 50 mg dose produces never-before-seen improvements in Parkinson's patients.
When the 50 mg data for Alzheimer's come out, it will have an effect on the stock price, good or bad.
In the hands of the FDA
If Anavex asks for emergency approval for Blarcamesine, that approval could come very quickly. Biogen/Eisai presented its Phase 3 Leqembi trial data in November; the FDA granted emergency approval in January based solely on the Phase 2 data.
Anavex will likely present and publish in a peer-reviewed journal the Phase 2b/3 data in Q1 2023. Emergency approval by the FDA could come in Q2 2023. I am thinking as early as May.
The FDA could also reject emergency approval or demand another trial. The FDA last week rejected Eli Lilly's Alzheimer's drug, Donanemab, for emergency approval. The FDA required a minimum of 100 patients for an amyloid-clearing drug, if the drug is to be approved for emergency approval. Eli Lilly, for an unknown reason, did not have enough patients. This demonstrates that the FDA, despite its declaration of Leqembi as a disease-modifying drug, also has rules in place that require higher bars for the more dangerous amyloid-clearing drugs. There is some balance there.
Ultimately, the FDA seeks efficacy and safety, and it takes into account the need for a drug. In the US, 6.5 million people suffer from Alzheimer's and they need an effective treatment. They do not have one. The FDA is likely willing to trade off a bit on safety in order to meet that need, as in the case of Leqembi.
When in May the FDA might have the opportunity to grant emergency approval to Blarcamesine, it will not have to compromise on safety, in my opinion.
Upon FDA emergency approval, Medicare may decide to pay for Anavex's Blarcamesine. And when that happens, the value of Anavex Life Sciences may exceed $15 Billion as discussed in my above mentioned article; and if one takes into consideration the Parkinson's and the Rett syndrome applications, the company may be worth $20 Billion.
I have not mentioned the Rett syndrome approval which may also occur in the first half of 2023. Upon approval, some Alzheimer's patients may be able to buy Blarcamesine for "off-label" use; they will have to pay cash, and it will be in a liquid form rather than a pill. But people like myself, whose mother has Alzheimer's, we may be happy to pay that out-of-pocket price. I am guessing it will certainly be less than one-third the cost of Leqembi's $26.5K price tag and does not require several brain MRIs or biweekly trips to the doctor.
The Rett syndrome approval may prove to be the catalyst for the stock skyrocketing, if it happens before any movement on Alzheimer's.
Conclusion
On January 12, CEO Missling declared that Anavex had enough cash for 4 years of continued operation. However, the value of the company may increase a great deal this year if its Rett application is approved in H1, if the FDA looks favorably at its Parkinson's drug in H1, or if the Alzheimer's drug is given emergency approval or put on track for conventional approval.
If Blarcamesine is approved, the value of the stock will skyrocket; its market cap should break through $10 billion upon final approval. The current market cap is well-below $1 billion.
The next shoe to drop may be the publication of a scientific journal article featuring the full data set for the Phase 2b/3 trial of Blarcamesine. I suspect this will happen within a month or so.
This article was written by
The Political Economist profile picture
The Political Economist
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I am the impassioned pundit at whyistherestillhunger.com. I have long studied and written about hunger, as it killed some members of my family (a generation before me). Currently I am dedicating much of my life to convincing people that hunger can be abolished this year. A relatively small investment of about $30 billion would end the holocaust of hunger and slow population growth tremendously (as mothers are convinced that their children will survive). I have also been studying and investing in alternative energy companies for several years. A generational shift in attitudes about the climate and air quality continues to move policy in the direction of cleaner energy.
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Disclosure: I/we have a beneficial long position in the shares of AVXL either through stock ownership, options, or other derivatives. I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it (other than from Seeking Alpha). I have no business relationship with any company whose stock is mentioned in this article.
Additional disclosure: I do not short stocks.
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georgejjl
04 Feb. 2023, 7:24 PM
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The average twelve-month price prediction for Anavex Life Sciences is $45.25 with a high price target of $80.00
www.marketbeat.com/...
Good luck and GOD bless,
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georgejjl
04 Feb. 2023, 6:27 PM
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Kun Jin
Vice President and Head of Biostatistics at Anavex Life Sciences
www.linkedin.com/...
EXCELLENT recent hire!!!
Good luck and GOD bless,
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cucumberbatch
04 Feb. 2023, 8:37 PM
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@georgejjl EXCELLENT recent hire!!!
more like a bureaucrat cashing in on his insider contacts.
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georgejjl
Yesterday, 5:05 PM
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@cucumberbatch Dr. Kun Jin was the Statistical Team LeaderStatistical Team Leader at the FDA/CDER and had worked there for 27 years. Dr. Jin deserves a lot of respect.
GOD bless,
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The Political Economist profile picture
The Political Economist
02 Feb. 2023, 9:54 AM
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CORRECTION: Rett pediatric "topline" results likely to be released in H2. The company announced today that enrollment had exceeded what they sought or needed. The adult Rett Syndrome trial was already completed and successful. I believe the company wants to wait until the pediatric results come out to seek FDA approval, but again, this is an even more urgent matter than the Alzheimer's application for Blarcamesine as these children often have a very short lifespan that is often punctuated by great suffering.
I think when I wrote the article above I thought that Missling would ask for approval using only the adult Rett trial data. Let's listen to the conference call on Tuesday and see what their plans are. I am wrong, based on past statements by the company. Thanks, bradscat.
From the pr: today announced the total enrollment of 92 patients with Rett syndrome for the ANAVEX(R)2-73 (blarcamesine) EXCELLENCE Phase 2/3 study in Rett syndrome patients ages greater-than or equal to 5 years to 17 (inclusive). This exceeds the original enrollment target and the Company expects to announce topline results from this study in 2H 2023.
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sparkmeister profile picture
sparkmeister
02 Feb. 2023, 12:24 PM
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@The Political Economist One possible strategy is to obtain Rett approval with the FDA, first, which would secure the Voucher ($100M), while also pursuing Rett and AD approvals in AU and EU.
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The Political Economist profile picture
The Political Economist
01 Feb. 2023, 4:03 PM
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NEWS: Anavex announces earnings and holds conference call on Tuesday morning. Listen to the call and then call your Congressman to tell them about the drug we need for our parents, uncles and aunts, and eventually ourselves. I will call my representatives that day too.
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s19104
01 Feb. 2023, 11:02 AM
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You keep saying emergency approval but no AD medication has emergency approval. In your article you state "Based on Phase 2 data alone, the FDA has granted emergency approval to the Biogen/Eisai (BIIB) Alzheimer's drug, Lecanemab" That is incorrect. The FDA granted accelerated approval (AA) as was clearly stated in the quote that followed the above statement. Emergency use authorization (EUA) is not AA. There are many differences between the pathways. You might want to acquaint yourself with public FDA guidance before your next piece of fiction. There are several expedited programs, AA being the one that allows drugs to gain limited approval earlier than typical. No AD drug will be approved through EUA and blarcamesine will have difficulty trying to get AA. To get AA, there must be a surrogate endpoint (biomarker) that has been shown to correlate with benefit. What biomarker will Anavex use for blarcamesine? Lecanemab may not be covered by Medicare under the AA but by the end of the year, it may have full approval and then be covered. It is not a great medication but will offer mild benefit to some patients and families. Blarcamesine appears to have mild benefit but not enough clinical effect was seen in the single small phase 2b/3 and a larger trial will be needed.
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UP & DOWN
01 Feb. 2023, 11:51 AM
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@s19104 Why didn't SAVA use Biomarkers in there most recent data release?
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s19104
01 Feb. 2023, 12:39 PM
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@up & DOWN They are going the more traditional route with2 large phase 3 studies in progress.
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UP & DOWN profile picture
UP & DOWN
01 Feb. 2023, 1:47 PM
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@s19104 But no P value ....means no Stat Sig ! Seems more and more like the SAVA FUD machine ship is slowly sinking.
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The Political Economist profile picture
The Political Economist
31 Jan. 2023, 2:00 PM
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Like I said, buried in the article above, Blarcamesine could in theory be approved by Medicare before Leqembi is approved; this is a result of the special rules regarding amyloid-clearing drugs. This would be a disaster for Biogen / Eisai, and would give Anavex first to market advantage.
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The Political Economist profile picture
The Political Economist
31 Jan. 2023, 1:59 PM
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recent news: from Benzinga: In the U.S., lecanemab was granted accelerated approval as a treatment for AD by the U.S. Food and Drug Administration (FDA) on January 6, 2023. On the same day, Eisai submitted a Supplemental Biologics License Application (sBLA) to the FDA for approval under the traditional pathway based on the results from the Phase III Clarity AD confirmatory study.
In Japan, Eisai submitted a marketing authorization application to the Pharmaceuticals and Medical Devices Agency (PMDA) on January 16, 2023.
In China, Eisai has initiated submission of data for a BLA to the National Medical Products Administration (NMPA) of China in December 2022.
Biogen moving fast to get approvals. The competition will speed up activity -- people will want alternatives, especially in Australia where the people already have knowledge of Blarcamesine. I talked to a SCIENCE magazine reporter who reported on Leqembi and he seems to think that Blarcamesine must be years behind Leqembi and cannot get approval any time soon. Things will move fast in the Alzheimer's realm; he didn't know alzhe drugs can be approved on Phase 2 data alone, I believe.
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badkindle46
31 Jan. 2023, 8:57 AM
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My questions: will the FDA approve the drug without the company having a US IND? There have been no US sites for AD and only a very small (n~20) in Rett. Also, how can you compare lecanemab to 2-73? There's been no H2H study and Anavex has yet to publicize some very important data.
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brad_scat
31 Jan. 2023, 1:20 PM
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@badkindle46 a usa IND is not needed when running foreign clinical trials as long as conditions set by the fda have been met, and they have.
Rett N will be about 110 after the 84 patient phase 3 pediatric trial is completed this spring.
The small N you are referring to was the adult pediatric trial, it is much harder to find adults living with rett vs children, due to the early mortality rate.
We know lecanemabs data, and it is not impressive. The ITT patients in the avxl study performed 40% better than those on lean i and that includes the less optimal dose.
Also, The pooled mid dose and high dose data showed 84% likelihood of declining 0.5 points or less. This is already better than lecanemab. The mid dose has had historically weak results and likely dragged down the average.
Taking it one step further, If you single out the high dose group, which is the data we are waiting for… in those with a positive response AKA responders I expect an AVERAGE of greater than -5 points in ADAS-cog which is incredible and blows away every treatment on earth, and the approved treatments by leaps and bounds.
From previous avxl genomic studies it is estimated 80-85% of patients respond positively to the drug.
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sts66 profile picture
sts66
31 Jan. 2023, 4:04 PM
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@brad_scat "The pooled mid dose and high dose data showed 84% likelihood of declining 0.5 points or less. "
Are you saying that 16% of patients in the drug group declined more than 0.5 points? "Likelihood" is a rather odd term to use when talking about efficacy - sounds like odds to me - not a placebo adjusted result with a p-value and CI's. If that 84% number has no p-value and CI associated with it, it's essentially meaningless from a clinical and statistical standpoint. Hope that doesn't make me sound like Sage Advisors, who generally ridicules all talk about efficacy from the trial.
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cucumberbatch
31 Jan. 2023, 4:12 PM
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@sts66 it's essentially meaningless from a clinical and statistical standpoint.
it's just gobbletygook. no trained biostat would ever utter such nonsense. they're just attempting to put lipstick on the pig.
here's the gag:
in math stats there's something called the 'likelihood ratio', so these knuckleheads are hoping to head fake the retail rubes into thinking that's what's on offer. it's not.
there's also, in inference, the maximum likelihood estimation. it's not that, either.
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bufnyfan1
31 Jan. 2023, 8:16 AM
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Failure to approve blacamesine by the FDA would just prove without any doubt that the FDA is being influenced by "Big Pharma". You can be sure Biogen won't be thrilled with the approval of a drug that is cheaper/safer/easier to take (orally vs IV) and better than Lecanemab. In fact, it is recommended that when patients are on Lecanemab that they undergo periodic brain MRIs to rule out any bleeding (one of the side effects). Just the annual cost of this kind of screening alone is far more expensive than being on blacamesine
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Davy Crockett
31 Jan. 2023, 11:41 AM
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@bufnyfan1 There simply aren't enough medical facility resources available to cover the AD patient load if twice monthly IV treatments plus periodic brain MRIs become the standard treatment.
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earljr1
30 Jan. 2023, 11:11 PM
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Since it would take a few seconds to poke the sort button to distinguish the 30mg group from the 50mg, we can only conclude that AVXL is intentionally leaving this info unrevealed. Why? And why do they imply that it takes a lot of time when we all know it doesn't?
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Sage Advisors profile picture
Sage Advisors
31 Jan. 2023, 8:36 AM
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@earljr1 Of course the first thing done by statisticians is to run the stats on the PRE-SPECIFIED endpoints. Yes, the results for the 30 mg, 50 mg and the placebo. If the data was so extraordinary, why not just report it. You would have to believe they had no time for the actual stats they were supposed to run based on the protocol but they had time to run silly stats not recognized by regulators. Quite a stretch of logic.
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The Political Economist profile picture
The Political Economist
31 Jan. 2023, 1:49 PM
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@Sage Advisors You seem to be the expert on this. How do you handle the various titrations that occurred between the patients -- they uptitrated, they down-titrated, some dropped out or switched perhaps to a different dose. Having dozens of professional shorters trying to create errors that aren't even there, do you think they would be very careful when they are trying to distinguish who is counted as part of the 30 and the 50 mg groups? Plus, if they are not required to divide the groups up immediately, why would they? Obviously they have more data of all sorts to report. Some of it may be better or worse. The new info reported on the 12th at J.P. Morgan was better than expected. I guess you assume that all of the bad news is coming later, and that they have been lying, deceiving and hiding the entire time, risking everything they have been working for for decades so that they can maybe have one of their buddies sell some shares while the stock is still up. This is not what these people are working for. That type of behavior belong to the shorts. They create a storm of controversy out of nothing so that they can make a short-term gain on a stock, they have no regulations on them as long as they can say they are journalists making honest mistakes. They sow doubt by posting ridiculous posts -- on articles like mine -- saying things like "They have no data" or "They are hiding data" or "they put a spin on the data" or they dragged out dog and pony show, when they have no evidence or logic behind their deceptions and no SEC regulation either. People like Missling have actual laws applied to them, not like people like you, or cucumber or me for that matter.
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cucumberbatch
31 Jan. 2023, 2:02 PM
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@The Political Economist risking everything they have been working for for decades
all they've accomplished, as any such micro-cap PhRMA, is syphon off lots of moolah from gullible retail plungers. there is a reason lamestream PhRMA (and, it appears, the medical community) has had nothing to do with AVXL and SAVA. 'normal' micro-cap PhRMA (with revolutionary tech, of course!) have multiple collaborations on their resume; making clear that what they've got 'Baby you want it!'. at least on the Yahoo! Finance page, nary a one. why might that be?
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ponymon
30 Jan. 2023, 9:27 PM
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Actually, the US has had some experience with Anavex 2-73 as it was used at several sites in the US for the phase 2 Rett Syndrome trial. Check out the various locations in the US that offered it by scrolling down to the bottom: clinicaltrials.gov/...
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User 6715991 profile picture
User 6715991
30 Jan. 2023, 6:23 PM
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Great analysis
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georgejjl
30 Jan. 2023, 5:26 PM
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The Political Economist,
This is a great article.
BE AWARE and BEWARD of FUD (FEAR, UNCERTAINTY, and DOUBT) from bashers.
Watch, listen and learn
jpmorgan.metameetings.net/...
www.anavex.com/...
Good luck and GOD bless,
George
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The Political Economist profile picture
The Political Economist
31 Jan. 2023, 1:50 PM
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@georgejjl Thanks for posting the links. Also, people should just explore on the AVXL website and read for instance the "hand-in-hand" journal article about Sigmar1 agonist action.
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UP & DOWN profile picture
UP & DOWN
30 Jan. 2023, 4:53 PM
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All the best to your investing success.
www.youtube.com/...
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winnnerwinnerchickendinner
30 Jan. 2023, 4:20 PM
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Very optimistic this drug truly supplies a benefit to this patient population. There was a lot of discussion around their trial results…have those concerns been put to bed or are we still waiting for a better understanding of the 2b/3 data?
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doctahJonez
30 Jan. 2023, 4:05 PM
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"Anavex will likely present and publish in a peer-reviewed journal the Phase 2b/3 data in Q1 2023." any source for this?
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doctahJonez
31 Jan. 2023, 8:13 PM
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@The Political Economist ?
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Sage Advisors profile picture
Sage Advisors
30 Jan. 2023, 3:54 PM
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"Blarcamesine seems certain to be approved based on Phase 2b/3 data." I respectfully disagree- The chances FDA approves this based on the data shown to investors is virtually zero IMHO. They would have to show FDA the data on the pre-specified endpoints, not combination data and not silly stats like how likely a patient was to improve. Post hoc derived results are not relevant in the regulatory process. They would also have to produce full safety data. Neither were provided for investors. When a company wont share with investors the data FDA will require, it is a red flag.
"When in May the FDA might have the opportunity to grant emergency approval to Blarcamesine, it will not have to compromise on safety, in my opinion." That is an opinion that is based on safety data that excluded 37 patients from the safety chart. So, the safety profile could be VERY different in those excluded patients.
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rx7no1
30 Jan. 2023, 5:42 PM
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@Sage Advisors all your points will be answered in the peer reviewed medical journal article.
Which will be published prior to or in conjunction with the NDA with the FDA.
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brad_scat
30 Jan. 2023, 10:38 PM
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@Sage Advisors they will show all of that data to the fda. What investors saw was a very preliminary readout that was created just 24 hours after they received full data, due to a trial site failing to lock the data on time.
They aren’t going to take the top line data from ctad to the fda and hope for approval??
They have 3 senior FDA officials on their team. They know what it takes to get approved. I’d trust them long before you. They are to going run a full genomic analysis for each patient. The data will be robust, and prove how effective the compound is from many different angles. Missling said they are going to aggressively pursue approval across the globe.
Blarcamesine has been safe and well tolerated through its history of clinical trials ranging from teenagers to 85 year olds.
You will be proven wrong soon.
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cucumberbatch
30 Jan. 2023, 10:58 PM
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@brad_scat They have 3 senior FDA officials on their team.
gee, that's sounds a lot like corruption!! :) one hopes you mean 'former FDA officials'????
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The Political Economist profile picture
The Political Economist
30 Jan. 2023, 3:19 PM
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In response to CucumberBatch, the FDA DID APPROVE of an Australian Covid drug test recently, so it has approved of Australian medical products. The FDA also has a long-term agreement with the Australian version of the FDA, as well as the EU, to cooperate on drug approvals so that billions in repetitive trials are not required.
The Australian government is likely to approve of Blarcamesine before anyone else in large part simply because the drug has gotten a great deal of positive publicity, including reports of individuals who have benefited greatly from the drug.
Also, there has been talk of "super-responders" to the drug in Australia and that will only encourage the Aussies to approve the drug quickly.
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cucumberbatch
30 Jan. 2023, 3:44 PM
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@The Political Economist there has been talk of "super-responders" to the drug in Australia and that will only encourage the Aussies to approve the drug quickly.
I would urge you to re-read your Stats 101 text. to wit: 'outliers' pull the mean. median much less so. so, what it means is - do folks mean the mean length of response to the drug, or the median? or neither, citing only the fact of the existence of outliers? I believe it's been just the last, as such has no clinical meaning. unless, of course, the sponsor can get very specific wrt outlier patient characteristics. but, of course, the sponsor would need to run another trial including patients with those characteristics. TANSTAAFL
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brad_scat
30 Jan. 2023, 10:40 PM
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@cucumberbatch
What are you going to say when their 509 patient trials has a larger number super responders whose disease course has been halted and even reversed?
Their lead clinician stated he has observed these effects in many individuals, himself, following his presentation at CTAD.
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cucumberbatch
30 Jan. 2023, 10:59 PM
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@brad_scat What are you going to say when their 509 patient trials has a larger number super responders whose disease course has been halted and even reversed?
about the same as some guy who claims to have climbed Everest in his boxer shorts. in winter. not much.
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ConfirmationBiasSuxs
30 Jan. 2023, 3:14 PM
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Great article, keep up the amazing work!, since you mention possible off label use I'm wondering if you have any information about the US "Right to Try" legislation passed back in 2018?... Does that allow people to start taking Blarcamesine now? And if the answers are positive for either question have you asked Anavex if they have any sales that are prescribed under the compassionate use doctrine? on a side note... did the Alzheimer's Ass. ever get back to you with an opinion on Blarcamesine?
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The Political Economist profile picture
The Political Economist
31 Jan. 2023, 1:54 PM
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@ConfirmationBiasSuxs Read my earlier comment regarding the Alzheimer's Association. The top scientist there had not looked at the initial results of Blarcamesine Phase 2b/3, but said that they support any drug that works and that the communications arm was to blame for the organization looking so pro-Biogen.
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sts66 profile picture
sts66
31 Jan. 2023, 3:42 PM
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@ConfirmationBiasSuxs Right to try just means a patient can either pay for a drug that might help them out of pocket or the company can donate the drug for free. And AFAIK it's restricted to life and death situations, not slow developing diseases like AD.
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smikhail profile picture
smikhail
30 Jan. 2023, 3:06 PM
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@The Political Economist
"I have not mentioned the Rett syndrome approval which may also occur in the first half of 2023."
Are you referring to FDA approval and/or Ex-USA? Any thoughts as to when AVXL will report on the EXCELLENCE trial?
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The Political Economist profile picture
The Political Economist
30 Jan. 2023, 3:22 PM
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@smikhail In our Rett syndrome program, we are nearing completion of the randomized, placebo-controlled EXCELLENCE Phase 2/3 study for the treatment of paediatric patients with Rett syndrome.
The above from Nov 28 earnings call transcript available on SA.
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smikhail
30 Jan. 2023, 5:12 PM
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@The Political Economist
What about my first question regarding Rett syndrome approval?
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brad_scat
30 Jan. 2023, 10:40 PM
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@smikhail I’ll play. I actually think the author is off on his rett timeline. The rett trial was still recruiting as of last month. So the 11 week trial will not be completed until end of Q1, data like by end of q2… then filing in 2H of 2023, approval possible at the very end of 2023 but probably early 2024.
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Downtown10 profile picture
Downtown10
30 Jan. 2023, 3:05 PM
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Nothing factually incorrect here that I see. Overall a well done article but, for a bunch of reasons (no US patient participation, modest trial size, extremely tiny Phase 2a trial size, FDA bias against small biotechs, choice of trial results measurement, unknown MOA, Sigmar-1 not universally acknowledged as a AD biomarker) wildly optimistic. I’ve been long AVXL for years, but my belief is that the chances of the FDA approving Blarcamesine for AD without an additional Phase 3 confirmatory trial are somewhere between slim and none. Could the Aussies approve prior to the FDA on this data alone? Possibly, I don’t know their history in such matters well enough to have an opinion, but such an occurrence must be rare.
The author has provided a very reasonable case for what the FDA should do, but is again, wildly optimistic IMO, when it comes to what the FDA will do.
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brad_scat
30 Jan. 2023, 10:36 PM
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@Downtown10 this trial was designed following updated EMA clinical trial guidance in 2016.
The responder analysis and trial design line up with what the EMA is looking for. I think that will be their first filing the. AuS and USA to follow
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sparkmeister profile picture
sparkmeister
30 Jan. 2023, 11:43 PM
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@Downtown10 fully expect the TGA (AU) and EMA (EU) to approve blarcamesine this year, then the compromised FDA will feel the pressure and be shamed once again.
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Downtown10
30 Jan. 2023, 11:59 PM
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@sparkmeister Hope you and @brad_scat are right!
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2959 profile picture
2959
30 Jan. 2023, 2:36 PM
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Any thoughts on the comparison to the BIVI (BioVie) pipeline?
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The Political Economist profile picture
The Political Economist
30 Jan. 2023, 3:14 PM
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@2959 I am not familiar enough to give you an opinion. Didn't Lane Simonian write on BIVI and AVXL recently?
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Lane Simonian
30 Jan. 2023, 3:38 PM
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@2959 I am working on an article that touches on Biovie's drug candidate NE3107 for Alzheimer's disease. NE3107 inhibits the phosphorylation of ERK (extracellular regulatory kinase) which limits oxidation, nitration, and neuroinflammation. To what extent that would modify the course of Alzheimer's disease and Parkinson's Disease has yet to be determined.
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2959
30 Jan. 2023, 3:41 PM
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@Lane Simonian Thanks, I will look for it and add you to my follow list. Take care.
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Lane Simonian
30 Jan. 2023, 2:34 PM
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Your articles add a great deal to our understanding of blarcamesine and to its chances for at least emergency approval.
Blarcamesine helps to limit the formation of amyloid (which may contribute to Alzheimer's disease at least in ApoE4 carriers), the removal of amyloid, inhibit the misfolding of tau protein (which inhibits neurotransmissions), prevent mitochondrial dysfunction, reduce neuroinflammation, oxidation, and nitration, inhibt the breakdown of acetycholine, maintain levels of critical neurotransmitters, allow for the regeneration of neurons, and greatly reduce the death of neurons. Matching the mechanism of action in early Alzheimer's disease with the likely positive results from the 50mg group gives one a great deal of hope.
Let's hope that Dunn and others at the FDA are rationale actors, not so wedded to a particular hypothesis of Alzheimer's disease or to particular companies, that they cannot approve a drug that should help many people.
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UP & DOWN
30 Jan. 2023, 4:59 PM
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@Lane Simonian www.youtube.com/...
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Lane Simonian
30 Jan. 2023, 5:46 PM
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@up & DOWN Good work by Jesse as always.
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sts66
31 Jan. 2023, 3:38 PM
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@Lane Simonian Blarcamesine acts on a whopping 11 different brain functions/actions? I think you're missing the word "may" in that 2nd paragraph.......
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The Political Economist profile picture
The Political Economist
30 Jan. 2023, 2:20 PM
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Regarding the ALZHEIMER'S ASSOCIATION, I spoke to one of their top scientists at length, and I am convinced that they are NOT fully dedicated to the amyloid hypothesis because they are funding a tremendous number of studies, mostly in Phase 1, and they kept pounding me with the "diversity" of their treatments funding.
The problem was, they did not seem to be aware of Blarcamesine's trial. They knew there was a trial, but they literally said to me, "Let me look it up." The most promising drug ever tested, and she has to look it up because they have not really read the trial results. That's the sad thing.
She kind of blamed the communications arm of the association for all the focus on the amyloid-clearing drugs -- that the scientific research arm was dedicated to any treatment that works.
Unfortunately the scientific arm informs the communications arm, in part at least, as to what drugs to show support for.
I am certain that when the full Phase 2b/3 data comes out, they will be focused on it like a hawk. If not, I will give them another call.
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Sage Advisors
30 Jan. 2023, 4:08 PM
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@The Political Economist The CTAD audience is filled with researchers in AD. When a company presents data, with nonsensical "endpoints" which differ from the actual pre-specified endpoints and labels them "primary endpoints", people take notice. When data is spectacular, you just present it in full and identify the actual endpoints. You are not going to fool an audience of experts by telling them patients are more likely to improve nor are you going to confuse them with endpoints that are post-hoc derived results. Clinical researchers know how to read data- when patients are missing from the safety data, they do not make assumptions like, "it must be safe." The stock's reaction, the lack of excitement from Alzheimer's foundation are both clear signs.
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brad_scat
30 Jan. 2023, 10:35 PM
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@Sage Advisors they didn’t have the full data. That is known and was clear.
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sparkmeister profile picture
sparkmeister
30 Jan. 2023, 11:05 PM
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@Sage Advisors that's the biggest bunch of FUD I ever read. Take note: Blarcamesine will be the next SoC for a host of neurodegenerative and neurodevelopmental diseases. The ineffective toxic MABs are toast.
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Goudadog
30 Jan. 2023, 2:06 PM
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Concise with a strong reminder this approach isn't about plaque and its not limited to Alzheimers. My mother had Parkinsons and one of the reasons the Michael J Fox Foundation is a financial supporter here. Rett is devastating, and Parkinsons patients have no resources for long term improvement, only a few drugs to deal with specific symptoms. My mother took them all, and continued to diminish over 10 years and was very aware of her decline. She had mild cognitive impairment, fairly serious short memory loss, physical declines associated with Parkinsons including falling, hand coordination, and issues with swallowing which were all disheartening, disabling, and for a once beautiful successful woman - embarrassing. Thank you for your organization in this article and the reminders to drugs recently approved with limited results which have individuals and the FDA grasping at straws.
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The Political Economist
30 Jan. 2023, 3:24 PM
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@Goudadog Frankly, their Parkinson's results look maybe as good as any of their results. People probably don't realize that their Parkinson's trial was placebo controlled! And the results are pretty amazing, considering the lack of treatments.
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rx7no1
30 Jan. 2023, 5:56 PM
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@The Political Economist The lack of a follow up Parkinsons Phase 3 trial is discouraging.
They talk of an imaging trial with support from the Michael Fox Foundation but then inaction of the follow through after two years is very troubling.
TGD also promised TL data on the open label trial extension of the phase 2 by end of last year and nothing!
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sts66
31 Jan. 2023, 3:33 PM
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@rx7no1 Wait a sec - AVXL finished their PD P3 2 yrs ago and have done nothing with it yet? WTF? Did they release the results? Something doesn't pass the smell test here.
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Small Pharma Analyst
30 Jan. 2023, 1:41 PM
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Since Rett syndrome is a rare disease, pricing will likely be quite high, similar to other rare disease drugs. Something like $300,000 per year. If approved for Rett, it won't likely be used off-label for Alzheimer's disease.
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The Political Economist profile picture
The Political Economist
30 Jan. 2023, 2:00 PM
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@Small Pharma Analyst Are you saying this because of economies of scale? The drug described as a "small molecule", and I do not know how it is synthesized. But it will be in liquid form for Rett. And it may be the preferred treatment. My sense is that 300k is too high, for preparing millions of doses. So, you're saying that if 26.4k females in the USA who have Rett buy this drug, AVXL will earn nearly 8 billion dollars in revenue. And the rest of the world? Add another 2 billion in revenue? I guess what you're saying is that no one will be administered the Rett drug. Do you have any evidence for the drug being that expensive?
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rx7no1
30 Jan. 2023, 5:59 PM
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@The Political Economist I recall Missling on one occasion mentioning $500 - 600,000 annual cost as being reasonable compared to other drugs for significant rare diseases with no approved drugs.
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brad_scat
30 Jan. 2023, 10:35 PM
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@The Political Economist Missling himself mentioned a range for potential rett price of 200k-600k a couple of years ago.
It does have to do with economies of scale regarding price. No companies would spend time and money researching and running trials for rare disease treatments without being granted the ability to charge a price that would reward them for their efforts.
Go Capitalism????????
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DawesR
30 Jan. 2023, 1:22 PM
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What is the estimated cost of treatment for Blarcamesine as compared to Leqembi?
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The Political Economist
30 Jan. 2023, 2:01 PM
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@DawesR My guess would be less than one-third. That's just based on the fact that it's a pill and hundreds of millions of doses would be likely produced each year. Economies of scale.
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sts66
31 Jan. 2023, 3:17 PM
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@The Political Economist I wouldn't be so sure of that - AVXL might try to charge what the market will bear - it has no incentive to undercut it's price with no competition around (yet).
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brad_scat
30 Jan. 2023, 1:08 PM
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Indeed.
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Stockdoc96
30 Jan. 2023, 1:02 PM
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While I think your time lines for AD, Rett and Parkinson's approval are the most optimistic possible, of course I hope you are right. One thing is clear, the FDA is bending over backwards to provide Alzheimer's sufferers with something (ANYTHING, apparently) to give them hope. But the data also needs to convince doctors to prescribe it and Medicare to cover it and I doubt that for either Biogen drug, at least to any great extent. One last thing, you did not emphasize enough that Biogen's drug(s) are INFUSION/IV therapy (that have a cost also, including time and the hassle of biweekly trips to the infusion center). I don't know who on this planet would prefer infusions to taking a pill once a day (blarcamesine).
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The Political Economist
30 Jan. 2023, 1:49 PM
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@Stockdoc96 I think that is the key here. The FDA knows it serves the American public and it must give them a chance at drugs to treat one of the most feared and loathed diseases among humankind. That's the key. Even the FDA knows they are being watched by someone, and it only takes a few people to make an enormous stink. Like me. I have led movements, changed institutions. I hope to start a movement for the lesser known Alzheimer's drugs, if necessary.
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brichnyc
31 Jan. 2023, 8:29 AM
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@The Political Economist Excellent job with this article. Thanks for doing the research, it’s appreciated. Big question, you stated “I hope to start a movement for the lesser known Alzheimer's drugs, if necessary”. Why not start the movement right now? We know that it will be a struggle so let’s amp up the pressure and exposure to Anavex now to get the visibility.
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The Political Economist
31 Jan. 2023, 11:15 AM
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@brichnyc Call your Alzheimer's Association to support this drug. They have their heads up their tails as they are focused on their own Phase 1 trials that they fund. I am already a nuisance over there. I am looking for an Alzheimer's organization that is more interested in fighting for their constituents. If you know of one, let me know.
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sierranvin
30 Jan. 2023, 12:41 PM
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A lot of blue sky here! I am long AVXL and hope for all the outcomes you project. Yet I fear the recent FDA insanity of ignoring the medical advisory panel and the varied, subsequent troubles may result in a constipated slowdown of FDA action. I must say I don't understand what's wrong at the FDA!
I can't stop wondering if they were bribed to approve Aduhelm.
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Carlos54
30 Jan. 2023, 4:24 PM
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@sierranvin I doubt “bribed”. More likely “group think”. They have heard for years about the analogue hypothesis. Their first Biogenesis approval stank so then an “improvement” on that treatment looked like a no brainer
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cucumberbatch
30 Jan. 2023, 5:13 PM
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@sierranvin if they were bribed to approve Aduhelm.
just remember: it wasn't the working scientists who wanted it approved, in fact many objected; it was the political appointees and the SES (look it up) who are beholden on the political appointees to keep their jobs.
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sparkmeister
30 Jan. 2023, 11:32 PM
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@sierranvin thankfully, there is TGA (AU) and EMA (EU) to provide first approvals this year, while the compromised FDA cleans egg off their faces.
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rbordogna378
30 Jan. 2023, 12:35 PM
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One can only hope you are correct. However, both the FDA and the Alzheimer’s Association seem fully invested in the plaque theory. The article written by Professor Adriane Fugh-Berman of Georgetown University and published in the Miami Herald is a devastating indictment of Leqembi, Aduhelm as well as the conduct of both the FDA and the AA.
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The Political Economist
30 Jan. 2023, 12:37 PM
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@rbordogna378 thanks for the heads up. I will have to read that article!
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Downtown10
30 Jan. 2023, 1:02 PM
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@rbordogna378 Here is a link to the article: www.miamiherald.com/...
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Ronny1703
30 Jan. 2023, 12:33 PM
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Great article and research. Many thanks. Agree with the author 100%. I just hope FDA acts as a neutral entity and not only working for big pharma in this case. And lets hope for the journal review soon. Dr. M was very confident in SFO and even had the courage to compare B vs L in his presentation. He wouldnt be doing such a thing at JPM conference if they did not have something to show for. I hope its all true what they are saying and know the consequences if not correct.
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The Political Economist
30 Jan. 2023, 12:39 PM
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@Ronny1703 thanks for the comment. After so many conferences, I forget that there's a certain gravity to presenting before these global finance institutes. You've got to be completely truthful and playing no games. After following Missling for so long, I trust him.
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The Political Economist
30 Jan. 2023, 12:30 PM
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NEWS ALERT: Japan put BIIB/Eisai's Leqembi on the fast track for approval after looking at Phase 2 and 3 results. Anavex's Blarcamesine could be approved first by the home-nation of Australia. That would not be surprising whatsoever. I would look out for an announcement by the Aussie government, as posted via an AVXL presser.
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cucumberbatch
30 Jan. 2023, 1:18 PM
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@The Political Economist Aussie government
update me if I'm wrong:
- most/all of AVXL's trial work was conducted there
- FDA is phobic about approving drugs with no USofA trials
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The Political Economist
30 Jan. 2023, 1:43 PM
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@cucumberbatch I believe some commenters on SA on AVXL boards have listed drugs that were approved that had foreign patients in its trials. So, my hunch is that FDA is not phobic. I don't have a percentage approval versus domestic trials data set for you.
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The Political Economist
30 Jan. 2023, 1:45 PM
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@The Political Economist If Australia approves of the drug, I do believe it will give a boost to U.S. approval. But like I said in the article, it has to do more with the need for the drug and the side effects. There is an enormous need, and there are milder side effects than Leqembi and Aduhelm. The FDA has approved foreign drugs before, and if it were to approve any foreign drug, it would be for a drug in great need with a better safety profile, from a nation that has high standards (like Australia).
Steve Bryson, PhD avatar
by Steve Bryson, PhD | March 17, 2022
UCB0599 | Parkinson's News Today | clinical trial | clinical trial graph illustration
Anavex 2-73 (blarcamesine), an investigational oral therapy for Parkinson’s disease dementia, led to clinically meaningful improvements within all four MDS-UPDRS assessments for patients treated daily at high dose, according to new data from a completed Phase 2 trial.
These benefits, in both motor and non-motor Parkinson’s symptoms, were also significantly tied to a rise in Anavex 2-73’s target receptor, called SIGMAR1, confirming the therapy’s mechanism of action and this receptor as a reliable biomarker of response.
Its developer Anavex Life Sciences now plans to launch a Phase 3 study of the therapy’s effects on cognition and other disease symptoms in patients with and without dementia, according to a company press release.
“I am impressed with the robust improvement of the MDS-UPDRS across all sub-score parts I-IV coupled with the biomarker correlated outcome measures and I support the implementation of the ANAVEX 2-73 Phase 3 studies in Parkinson’s disease and Parkinson’s disease dementia, respectively,” said the trial’s principal investigator, Jaime Kulisevsky, MD, PhD.
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New data were presented as a poster by Kulisevsky, a professor of neurology at the Medicine Autonomous University of Barcelona and director of the Movement Disorders Unit at Sant Pau Hospital in Spain, at the AD/PD 2022 International Conference on Alzheimer’s & Parkinson’s Diseases and related neurological disorders held March 15–20.
The poster is titled, “ANAVEX2-73 (blarcamesine) – Analysis of Movement (MDS-UPDRS) and Cognitive (CDR System) Pharmacodynamic-Biomarker Outcome Measures of Placebo-Controlled Phase 2 Trial in 132 Parkinson’s Disease Dementia Patients.”
Anavex 2-73 is a small molecule activator of the receptor SIGMAR1, which is diminished in the brains of Parkinson’s patients as well as those with Alzheimer’s and Rett syndrome. The protein receptor is involved in various processes related to maintaining healthy brain cells.
By activating SIGMAR1, Anavex 2-73 aims to restore brain cell health and slow neurological decline by targeting protein misfolding and aggregation, lessening the resulting inflammation, problems in energy-producing mitochondria, and oxidative stress — an imbalance between the production and clearance of toxic reactive species generated by metabolism that are harmful to cells.
The proof-of-concept Phase 2 ANAVEX 2-73-PDD-001 study (NCT03774459) evaluated the therapy’s safety and early effectiveness in 132 adults, ages 50–85, with Parkinson’s disease dementia (PDD). Participants, recruited at multiple sites in Spain and Australia, were randomly assigned 30 or 50 mg oral capsules of ANAVEX 2-73 or a placebo capsule, once daily for 14 weeks (about 3.5 months).
Previously reported results showed Anavex 2-73 significantly improved several cognitive skills, including episodic memory, and lessened REM sleep behavior disorder. This disorder, characterized by physically acting out dreams, is associated with greater cognitive impairment and a higher risk of dementia. The therapy was also reported to be safe and well tolerated at high dose, with a safety profile superior to that of other common dementia medications.
More recent data confirmed these cognitive and sleep benefits and also showed the therapy’s high 50 mg dose led to a 10.98 points drop in the MDS-UPDRS total score, indicating an easing in disease severity across several measures. At the same time, the total score in the placebo group rose by 3.53 points, representing a 14.51-point difference and an 18.9% relative improvement over 14 weeks.
Anavex 2-73’s use also resulted in a significant increase in SIGMAR1 messenger RNA (mRNA) levels, the molecule that carries genetic instructions to make SIGMAR1. This rise was associated with gains in attention assessments, and with better MDS-UPDRS total scores and those of MDS-UPDRS Part III, which tests motor abilities.
New findings describe the details of each MDS-UPDRS assessment section in high-dose patients.
In MDS-UPDRS Part I, measuring non-motor experiences of daily living including cognition, mood, psychosis, and sleep issues, 12 out 13 items assessed improved (92.23%). MDS-UPDRS Part II examines motor experiences of daily living, from speech and eating to doing hobbies, and 10 out of 13 items improved (76.92%).
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Cognitive Problems Varied and Frequent in Late-stage Parkinson’s
In Part III for motor function, ranging from speech to hand movements, posture to gait, 30 out of 34 items showed score gains (88.23%), while five out of seven items (71.42%) improved in MDS-UPDRS Part IV scores for motor complications like dyskinesia (uncontrolled movement) and levodopa treatment “off” periods.
A dose-dependent increase in scores for episodic memory — the ability to remember new shared information and personal experiences — was also reported. While the placebo group scores fell by 20.82 points, the scores for those treated with Anavex 2-73 rose by 21.40 points, a 44.22-point improvement in episodic memory scores.
“ANAVEX 2-73 (blarcamesine) demonstrated dose-dependent efficacy for both motor impairment (MDS-UPDRS) and cognition … which correlated with SIGMAR1 mRNA as a pharmacodynamic biomarker, respectively,” said Christopher Missling, PhD, president & CEO of Anavex. “These results support continued development of ANAVEX2-73 in Parkinson’s disease and Parkinson’s disease dementia.”
Patients who finished ANAVEX 2-73-PDD-001 were invited to continue or start treatment with Anavex 2-73 in ANAVEX 2-73-PDD-EP-001 (NCT04575259), a 48-week (almost one year) extension study of the therapy’s long-term safety and efficacy, as well as potential treatment effects on gut bacteria. It is due to be finished in June.
“We would like to thank all the patients and participating families as well the investigators and clinical site coordinators for their dedication to this study,” Missling added.
Up to 80% of Parkinson’s patients are estimated to develop disease-related dementia, which affects mental abilities that include memory and attention, completing tasks, and making judgments, and treatments options are limited.
“PDD [Parkinson’s disease dementia] is a debilitating disorder with significant co-morbidities and there has not been a mechanistically novel medication approved for PDD in over 20 years,” Kulisevsky said. “Hence, new therapies are urgently needed to alleviate this suffering and disability.”
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How Well Does Anavex's New Alzheimer's Drug Compare Against Biogen's New Drug?
Dec. 21, 2022 1:08 PM ETAnavex Life Sciences Corp. (AVXL)BIIB, LLY, SAVA15 Comments
Summary
The Phase 2b/3 trial of Anavex's Blarcamesine demonstrates major, statistically significant effects in slowing Alzheimer's Disease.
The drug slowed cognitive decline by about 45% over 48 weeks on the ADAS-Cog test, a measure of cognitive ability. It appears more effective than Biogen's Lecanemab.
A number of patients on the drug demonstrated cognitive/behavioral IMPROVEMENT (rather than slowing of decline); the initial readout of results indicate some showed extreme improvement (a super-response).
The patients in Anavex's Blarcamesine trial were substantially more cognitively impaired than those in Biogen's Lecanemab trial.
Dementia and Occupational Therapy - Home caregiver and senior adult woman
FredFroese/E+ via Getty Images
Anavex (NASDAQ:AVXL) has just completed a Phase 2b/3 trial of its new Alzheimer's drug, Blarcamesine, and the company reported initial results on December 1. It will report the full set of results and data before meeting with the FDA about what to do next.
In November, Biogen (BIIB) published its full set of results for its new Alzheimer's drug, Lecanemab.
Analyzing both sets of results, it seems apparent to me that dementia patients will prefer Anavex's Blarcamesine, based on both performance and side effects (see below).
[In separate 48-week tests, Blarcamesine trounces the currently available Alzheimer's treatment, Donepezil, in performance]
In Blarcamesine's 48 week trial, patients on the drug benefited from a 45% reduction in cognitive decline (versus placebo) based on the Alzheimer's Disease Assessment Scale Cognitive Subscale (ADAS-Cog) scores of patients. The ADAS is a test of thinking ability and memory. The worse your brain is working, the higher you score on the test. Those who took the placebo got worse by 4.11 points and those who took Blarcamesine got worse by only 2.26 points over 48 weeks.
The patients in the Anavex Phase 2b/3 trial started the trial with an ADAS-Cog of around 29; this is a serious level of cognitive impairment, and this group typically gets worse by about 4.5 points in a year's time. So, the 2.26 point decline among those treated with Blarcamesine represents about a halving of decline compared to the untreated.
Some patients taking Blarcamesine in their Phase 3 trial actually improved, rather than reducing decline. And those individuals who did improve, according to Anavex, improved by a whopping 4.06 points on average on their ADAS-Cog scores! This is an absolute improvement over their individual baseline measurements.
A 4-point improvement versus a 4-point decline? The 8-point difference can mean the difference between being normal and being diseased. Stunning.
Those taking Blarcamesine were divided into two equal groups of 169 patients. One group took 30 mg of Blarcamesine each morning and the other group took 50 mg each morning. In the previous trial, (Phase 2), the drug was more effective at the 50 mg dose than at the 30 mg dose. The latest trial was a Phase 2b/3 trial and may lead to FDA approval of Blarcamesine.
The results seem to indicate that those taking the 50 mg dose of Blarcamesine may have benefited much more than those who took the 30 mg dose each morning.
Blarcamesine also reduced decline in overall impairment by 27% as measured by the Clinical Dementia Rating Scale–Sum of Boxes (CDR-SB), a more global measure of cognition and behavior. This is very impressive, however, it is not as impressive as Blarcamesine's performance regarding the ADAS-Cog, a test that is purely focused on cognition and memory.
Perhaps Blarcamesine does not improve everyday functioning as much as it improves brain function. The Alzheimer's Disease Cooperative Study – Activities of Daily Living Scale (ADCS-ADL) measures performance of patients' daily living habits, based on caregiver interviews regarding the previous four weeks. Anavex did not report the mean change in ADCS-ADL.
Anavex only stated that those taking Blarcamesine were 167% more likely to improve their ADCS-ADL score by at least 3.5 points than were those on placebo pills. This means that if 12% of the placebo group improved their scores by at least 3.5 points, then about 32% of those taking Blarcamesine improved their scores by a very practically relevant 3.5 points or more on a 78-point scale. Of course, without any medication, patients are expected to decline in their performance.
Nevertheless, the lack of complete information seems to indicate that the overall ADCS-ADL numbers were not better than those of Biogen's Lecanemab, to which Anavex actively compared its drug in its most recent public presentation.
Comparing Blarcamesineemine And Lecanemab In Treating Alzheimer's Disease
While Anavex (AVXL) produced a partial readout of results for its daily pill, Blarcamesine, on December 1, Biogen (BIIB) produced a full readout of Phase 3 trials for its vaunted new biweekly intravenous treatment, Lecanemab, in November.
The results for Biogen's Lecanemab are encouraging despite some people suffering terrible side effects. But if Lecanemab's results were encouraging, then Blarcamesine's results are downright exciting.
Regarding the ADAS-Cog Scores. Cognitive decline was measured by the difference in change in the ADAS-Cog score versus change in ADAS-Cog score in the placebo arm over 48 weeks. In both studies, the placebo arm deteriorated in cognition at a faster rate than the treatment arm. Blarcamesine reduced deterioration by 40% more than Lecanemab at 48 weeks.
Furthermore, the Blarcamesine patients started off their drug trial with a good deal more cognitive dysfunction than the Lecanemab patients. The average ADAS-Cog scores of the Lecanemab trial was 24.45. The average ADAS-Cog scores of the people being administered Blarcamesine was 28.75. That's a 4.3 point difference, a very substantial difference in starting points.
Blarcamesine is 40% more effective than Lecanemab at 48 weeks, and on patients who are significantly more cognitively impaired. To be fair Lecanemab's trial continued for another 7 months and continued to slow impairment. Blarcamesine's trial ended at 48 weeks, and patients have the option to continue treatment in another study; will Blarcamesine continue to hold its 40% lead over Lecanemab? It is unclear, but it seems one's first year of Alzheimer's treatment should be on Blarcamesine.
Regarding the CDR-SB. The Blarcamesine patients were suffering from greater global impairment than the Lecanemab patients, as measured by the CDR-SB. At BASELINE (at the start of each study) the Blarcamesine patients had an average CDR-SB score of 3.81 versus Lecanemab's 3.17, representing significantly more impairment among the Blarcamesine group.
The Blarcamesine patients at baseline were suffering from Very Mild Dementia or Mild Dementia, while patients in the Lecanemab trial were suffering from Very Mild Dementia, Mild Dementia, but also "Questionable Impairment" (very little impairment, if any). See this link for a full discussion.
In this context, it is quite remarkable that the Blarcamesine patients reduced their cognitive decline by 27% over 48 weeks, while Lecanemab produced a similar 27% reduction in cognitive decline, except it took Lecanemab over 78 weeks (18 months). What would Blarcamesine accomplish given another 7 months?
Anavex hints that the drug would continue to reduce decline such that by 78 weeks, Blarcamesine would have a healthy lead over Lecanemab. The suggested logic is, if Blarcamesine at 11 months is equal to Lecanemab at 18 months, then given an equal amount of time to work, Blarcamesine should stretch to at least a 50% lead over Lecanemab.
Regarding ADCS-ADL. It is on the ADCS-MCI-ADL that Biogen's Lecanemab produced its best results. Those who took the drug saw a 37% reduction of decline compared to placebo over the course of over 78 weeks. Some strange numbers hang over the results. Men reduced their decline by almost 3x what women did. And Hispanics reduced their decline by about 3x-8x what non-Hispanics did (3x in the US and 8x outside of the US). Hispanics made up a major portion of their trial population, while Blacks did not.
In their initial readout, Anavex did not present much data on its ADCS-ADL results, one of their main endpoints. The company will release the full data set, including all the ADCS numbers before they submit a paper for publication in a peer-reviewed journal and before they meet with the FDA to discuss approval.
Perhaps the results of the ADCS were disappointing. This possibility is contradicted by a statistic the company did report: those who took Blarcamesine were 167% more likely to improve their ADCS-ADL score by 3.5 points than placebo.
Alzheimer's patients, especially those as deteriorated as the ones in the Blarcamesine trial were, are expected to get worse over the course of 48 weeks unless they are given a placebo or medication. In this case, I would expect very reasonably that maybe 12% of the placebo group improved 3.5 points on a measure that has far more to do with morale and mood than the ADAS-Cog. For instance, one question asks the caregiver how much help does the patient need in eating? The more optimistic one feels, the more likely one will refuse help and find a way to eat even if it requires a great deal of effort. Placebos provide optimism.
So, if 12% of the placebo arm improved by 3.5 points, then more than 32% of those who took Blarcamesine improved by 3.5 points or more. If that is the case, then a major portion performed magnificently with the help of Blarcamesine.
What about the other two-thirds? The ADCS is a questionnaire taken by the caregiver regarding the previous four weeks of helping the patient. In a trial that lasted only 48 weeks and for a psychotropic medication that may take numerous weeks to ramp up, the 44th week may not have been so pretty as the 47th week. Plus the caregiver may have their own biases. I would consider the ADCS scores to be the least reliable of the three measures that Anavex used as endpoints.
Regarding Side Effects. Blarcamesine trounces Lecanemab. About 3% of those who took Biogen's drug suffered from symptomatic brain hemorrhaging. Many more suffered asymptomatic brain hemorrhaging as well as noticeable brain swelling. Such symptoms may not prevent millions of desperate people from taking Biogen's Lecanemab, if it is approved and if there is no other alternative.
But 3% of one million is 30,000 people who must get treated or examined for brain hemorrhaging at an advanced age.
Further, two people in Biogen's Lecanemab study died under circumstances that suggested brain hemorrhaging contributed to their deaths. The doctor who performed one of the autopsies had this to say, as reported by Fierce Biotech.
Rudolph Castellani, a Northwestern University Medical Center neuropathologist who autopsied the body at the request of the patient’s husband, is quoted in Science as being unequivocal about the role lecanemab played in the death. Talking in a personal capacity, Castellani is reported as saying: “There’s zero doubt in my mind that this is a treatment-caused illness and death. If the patient hadn’t been on lecanemab she would be alive today.”
Having one patient die due to brain hemorrhaging, a known side effect of Lecanemab, represents a tiny fraction of the patient population.
Biogen reports that 859 patients took Lecanemab. If only 1 patient dies for every 900 patients, and 3 million people desperate for a cure decide to take Lecanemab, then 3,333 people will die from this Lecanemab side effect. While millions will certainly find the risk acceptable, it does seem like an avoidable catastrophe (avoided by taking the safer drug).
Because of these brain damage risks, those taking Lecanemab must get MRI tests done on their brains on a regular basis to check on the common side effect of brain swelling (a 600% increase in risk of brain swelling compared to placebo).
And finally, Lecanemab is taken through an IV infusion into a vein, every two weeks at the doctor's office. This can result in injection problems. And a lot of hassle and expense.
Blarcamesine is a once-daily pill, and patients in the trial were required to take the pill in the morning. Some of the patients complained about dizziness and confusion, and a small fraction of patients dropped out due to these side effects. Anavex suggested that some of these symptoms may be alleviated by taking the drug at night rather than in the morning. Interestingly the complaint of "falling" was reduced among those taking the Anavex drug. No drug-related deaths were reported.
Allowing Patients To Use Blarcamesine Rather Than Lecanemab May Save Thousands Of Lives.
Some Patients Improved Rather Than Reduced Decline
Biogen reported no actual patients improving after using Lecanemab or using placebo. This does not mean that there were no patients in their trial who improved. I would expect at least 10% of their patients under placebo to have improved. The placebo effect is powerful and it is the most consistent effect in all drug trials. The sense of optimism one feels under placebo can be especially powerful in helping patients being measured in their behavior and to a lesser degree their cognition.
Improvement on any measure was not an endpoint that Biogen claimed for its trial.
Anavex claims that substantial, clinically relevant improvement is one of its goals. And its measure for this is the probability that one will actually improve rather than slow decline while using its drug, Blarcamesine, versus placebo. In this measure, which some people find little use for, Anavex succeeded spectacularly.
On the ADAS-Cog, Blarcamesine-takers were 85% more likely to improve their scores by at least .5 points, a level of improvement that Anavex claims is noticeable in one's quality of life. Based on this statistic I am happy to buy some Blarcamesine for my mother, who has Alzheimer's, and myself too, when I show signs.
On the ADCS-ADL, the measure of everyday habits, Blarcamesine-takers were 167% more likely to have improved by at least 3.5 points, indeed a substantial improvement. And of course, this makes me want to utilize the drug even more. I like those odds.
But, for a traditional drug trial, these numbers are not what many scientists want to see. They are more interested in numbers such as the mean change in ADAS-Cog relative to placebo, as presented and discussed above.
30 mg Vs. 50 mg Of Blarcamesine And Super-Responders
FOR THOSE ON BLARCAMESINE WHO DID IMPROVE their ADAS-Cog scores, the average improvement was an amazing 4.06 points. This was weird. The overall average change among those taking Blarcasemine was a deterioration by over 2 points. How can these two numbers be part of the same drug trial?
If we assume that the distribution of changes in ADAS scores is normal -- a normal distribution -- then I would expect the average improvement to be closer to 1 point. There should be a lot of 1-point improvements, fewer 2 or 3 point improvements, and even fewer 4 or 5 point improvements.
One possibility is that it is a very flat curve on the side that represents improvement and a very sharp drop-off on the other side of the bell curve. The tail on the side of improvement must be very long and would likely have to extend beyond 10.
Of course, if one improves one's ADAS-Cog from 30 to 20 over the course of 48 weeks, this would likely be called a miracle.
Another possibility is that there are two clusters of those who improved. Perhaps the people who took 30 mg improved by 1 point on average. And perhaps among those who took the 50 mg dose, there were also some who improved by only one point or so, but rather than there being a "tail" on the curve, there is another cluster of improvers who improved by an average of 7. If you want an average of 4, after all, and you have a cluster of 1's, you have to have an equivalent cluster of 7's, or a smaller cluster of say, 10's, or three times as many 5's than 1's. The last case does not seem to gibe with the overall average.
This hypothetical group who improved by an average of 7 points or more may be called "super-responders." I am not validating any unverified blogs that claim researchers have reported "super-responders". I am ONLY looking at the data, and I am trying to understand how the average person who improved did so by over 4 points. The simplest explanation is the emergence of super-responders, who likely benefit far more than others due to genetic factors or because of the nature of their disease.
Of course, I am willing to go to many lengths to find out if my mother or I are super-responders. I want access to the drug, and so do many others.
Thoughts On Why The Stock Tanked
In my opinion, Anavex stock has not zoomed up based on the initial results of the Phase 2b/3 trial because:
1. Anavex did not provide the mean change in ADCS-ADL scores versus placebo; they only provided the statistic that those who took Blarcamesine were 167% more likely to improve their scores by 3.5 points. There may be some level of poor performance on this endpoint.
2. Immediately after Anavex published their data on December 1, many powerful "reporters" and "influencers" began claiming that Anavex's numbers were incorrect. Some of these influencers had a reputation for "bashing" companies. The chief accusation was that Anavex purposefully, or accidentally, made a simple subtraction error and the actual change in mean ADAS-Cog scores was less than the 45% reported.
The next day, CEO Christopher Missling explained how the ADAS-Cog calculations were made in an Investors Business Daily article. The explanation was expanded upon in a public presentation on December 5. One subtracts the final ADAS-Cog score from the original score for each individual; and then one finds the average of these individual differences. If there was no final measurement, then the individual difference was omitted. Makes sense, right?
Writers continued to claim that Anavex calculated their numbers wrongly. Interestingly, none of these meticulous data-combers, as they might characterize themselves, said anything about the glaring contradictions in Biogen's Lecanemab presentation. For instance, on two separate lines, both on page 34 of their presentation, Biogen stated that use of Lecanemab accelerated the cognitive decline of Hispanic and Black patients by 222% and 221%, respectively, compared to placebo. On those same respective lines, Biogen claimed that these apparently terrible results represented a slowing of cognitive decline relative to placebo.
3. Biogen's Lecanemab's successful Phase 3 trial was covered by all major mass media outlets, both upon presentation of their initial results as well as the final presentation of results. Famed financial analyst Jim Cramer has spoken extensively on both of Biogen's Alzheimer's drugs, sometimes being quite critical.
Anavex's Blarcamesine's successful Phase 3 trial was covered only by financial opinion and news outlets, and no other media outlets.
The Alzheimer's Association has 13 press releases regarding Lecanemab documented on its website. It has zero regarding Blarcamesine. As I continue to communicate with the Alzheimer's Association, I have not yet met anyone who has heard of Blarcamesine, nor anyone who has called me back regarding my questions about the drug.
Some of the influencers who speak on Anavex have been critical or accusatory with little evidence. "@InvestorsClubSpringer" is one live-streaming investing "guru" who favors Cassava Sciences over Anavex; he produced a number of videos on AVXL, but the most amusing one is "LLY and AVXL Sabotage SAVA? Five Biotechs Set To Double, and One Going 179x." Watch the first three minutes to get the gist of the conspiracy theories he hints at; you decide if he has presented any real evidence.
The Financial Potential
Worldwide 55 million people suffer from Alzheimer's disease. I believe that this number is an underestimate, as many people who suffer from Alzheimer's are never diagnosed.
If one out of eleven afflicted people, or 5 million people, pay for Blarcamesine, and they each pay $4000 per year, mostly in the high and middle-income nations, then that represents $20 billion per year in revenue.
If Blarcamesine is approved for the entire spectrum of cognitive impairment, then the numbers will increase. If Blarcamesine is prescribed as a preventative measure for those at high risk of Alzheimer's, that's an additional source of revenue.
When Biogen presented its initial results for its Phase 3 Lecanemab trail, the company's market cap increased by about $14 billion, the share price increasing from about 200 to 300 dollars. The stock has dribbled downward since around the time of the Anavex announcement; this may or may not be coincidental.
Health insurance companies will prefer Anavex's Blarcamesine over Biogen's Lecanemab, as widespread use of the Biogen drug may result in millions of additional MRIs each year, in order to monitor for brain hemorrhaging caused by Lecanemab. Also, Lecanemab may cause thousands of deaths and possible lawsuits.
Blarcamesine seems to be a good deal more effective than Lecanemab in slowing cognitive decline.
Blarcamesine also seems likely much better at actually improving cognition.
Blarcamesine certainly presents far better, non-lethal side effects.
My being at high risk of dementia, I would certainly prefer trying Blarcamesine for a couple of years before even considering Lecanemab.
Financial Risks
Some have said that Anavex has presented information that is not correct. If this is the case, and the drug actually does not work for Alzheimer's, then the value of the company may be limited to the 100s of millions, assuming that it will be approved for the Rett syndrome treatments (already-successful Phase 3 trials). Note that Anavex, via a Phase 2 trial, has demonstrated promise in treating Parkinson's Disease as well. A Fragile X treatment (orphan drug designation) and other treatments are further upstream.
If the ADCS-ADL scores turn out to be disappointing, but the ADAS-Cog and CDR-SB scores remain what they have been reported, the FDA will still approve Blarcamesine for Alzheimer's treatment, in my opinion. In this scenario, Blarcamesine would be approved on the grounds that it slows cognitive decline even if it does nothing to improve the eating or shopping habits of patients. In fact, it would be approved on the basis that it slows cognitive decline better than any known drug as of yet.
If Anavex needs to be subsumed by a Big Pharma corporation such as Eli Lilly (LLY), then Anavex may be bought out at a lower stock price than it would have otherwise reached if it were to market Blarcamesine on its own. Lilly could easily front $14 Billion dollars (based on the Biogen numbers above), and profit handsomely. Lilly is worth $342 Billion as of this writing.
Price Targets
Cantor Fitzgerald has a price target of $11 on AVXL stock, and Jones Trading believes AVXL will reach $80. I would prefer not to opine on a price target for Anavex stock. It is such a binary situation.
Given that, I believe that if the FDA rejects Anavex's Alzheimer's application, and if it only has the other ongoing drug trials to fall back on, the stock is worth 9 dollars a share, until one of its drugs is approved by the FDA. The Rett Syndrome application is worth in the 100s of millions and a Parkinson's approval is worth in the billions. The stock trades in the mid-8s as of this writing.
If Blarcamesine is approved for Alzheimer's, I believe the stock is worth over $180 per share based on the $14 billion estimate, and not including the value of the treatments for Rett, Parkinson's, Fragile X, and others. Please investigate the exciting Phase 2 placebo-controlled trial of Anavex's Parkinson's treatment, which may be worth billions, in my opinion.
The remaining data for the Blarcamesine drug trial might be made available during Anavex's presentation at The J.P. Morgan Healthcare Conference on January 12, 2023. The Anavex session starts at 8:15 a.m., Pacific Time.
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I found this interesting:
MayoMobile
Re: dia76ca post# 390497
Thursday, December 08, 2022 3:12:59 AM
Post#
390518
of 390809
"Funny, I discussed this topic to some degree with Dr. Macfarlane. Discussed the differences between U.S. and Australian healthcare coverage and he mentioned that the TGA is extremely hesitant to approve the antibody drugs due to their enormous cost. He said there isn’t enough efficacy for the TGA/Australian government to fully buy in.
This is one of the reasons I hit on lower cost in my CTAD summary. While exact price is unknown, I have hypothesized that drug will cost NO MORE than $10,000 annually per patient. That is an immense cost savings over Aduhelm (and most likely future Lecanemab sales). Like I said, TGA has a lot to gain."
Will Dr. MacFarlane take part in the CC tomorrow?
Hey Mike,
You guys may find AEMD a good swing/trade. Just released a manuscript that shows removal of covid in vivo from the blood with a filter. Low floater 15m. Just thought Id let you know...still holding HGEN. GLTA
Is the trial even listed on clinical.gov yet? if not why? tia
No big deal. I was curious if it was some sort of running joke between them, guess not. I am long the stock.
Just listened to the most recent CC, did Ben refer to Vanessa Luna, as Vanessa Williams? Not sure what to think. Anyone?
Nice buy and move off the 8.5$ bottom. Any thoughts on when ChargeSavvy acquisition closes?
Call the company and express your concerns then report back. Ben is a nice guy give it a try.
Visa CEO Al Kelly Interview: https://www.cnbc.com/latest-video/
Maybe one of the big partnerships will be strategically PRd and we get traction to meet the bid requirement for uplist.
M8,
This link might help. GL
Investorara15
Let me try that again.
Quote from your article:
“It goes without saying, to the extent a specific digital currency becomes a recognized means of exchange, there's no reason why we cannot add it to our network, which already supports over 160 currencies today,” he added. (Those are fiat currencies.)
"It’s a clearer version of a statement that Kelly made in November, at which time he suggested that Visa “could see digital currencies running on the Visa network on a more regular basis,” albeit “a number of years out.”
This change of timeline mentioned by the Visa CEO seems to be recent around the time GBOX gen3 was announced. This is very interesting!
Thanks for sharing.
Quote from your article:
"It’s a clearer version of a statement that Kelly made in November, at which time he suggested that Visa “could see digital currencies running on the Visa network on a more regular basis,” albeit “a number of years out.”
This change of timeline mentioned by the Visa CEO seems to be recent round the time GBOX gen3 was announced. This is very interesting!
Thanks for sharing.
Page 10 Nasdaq Capital Market: Financial and Liquidity Requirements
Companies must meet all of the criteria under at least one of the three standards below
https://listingcenter.nasdaq.com/assets/initialguide.pdf
Any ideas which standards test the company has their sights on?
I recently picked up shares in GBRX looking foward to this company growing into something big. Thanks to everyone for their contributions and good luck investing. Here's some additional info on S-1 Underwriting and Lock-up Agreements:
"The Company, each of our directors and executive officers, and our 5% and greater stockholders, have agreed not to, subject to certain limited exceptions, offer, pledge, sell, contract to sell, grant any option to purchase, or otherwise dispose of our common stock or any securities convertible into or exchangeable or exercisable for common stock, or to enter into any hedge or other arrangement or any transaction that transfers, directly or indirectly, the economic consequence of ownership of the shares of our common stock, in the case of the Company for a period of 365 days after the date of this prospectus, and in the case of our directors and executive officers and our 5% and greater stockholders for a period of 180 days after the date of this prospectus, without the prior written consent of Kingswood."
GreenBox POS To Acquire ChargeSavvy, A Specialty Retail Payment Processing Company
January 25, 2021
An All-Stock $31.2 Million Transaction Agreed to at Significant Premium of $2.00 Per Share of GreenBox POS Common Stock
Transaction is Immediately Accretive Adding Approximately $14 million in EBITDA and $500 Million Annually in Processing Volume
SAN DIEGO, CA / ACCESSWIRE / January 25, 2021 / GreenBox POS (OTCQB:GRBX) ("GreenBox" or "the Company"), an emerging financial technology company leveraging proprietary blockchain security to build customized payment solutions, has entered into a non-binding MOU to acquire ChargeSavvy LLC, a financial technology company specializing in payment processing and POS systems, for total consideration of $31.2 million in restricted GreenBox POS common stock.
The transaction, reflecting $2.00 per share of GreenBox stock is expected to be immediately accretive. The all-stock transaction is subject to the completion of an audit of ChargeSavvy's financial statements and customary closing conditions.
"ChargeSavvy's large footprint across multiple verticals, most specifically retail, makes for an ideal opportunity to grow together," said Jeff Nickel, Chief Operating Officer of ChargeSavvy. "Combining GreenBox's Gen-3 proprietary block-chain technology with our expansive processing portfolio presents significant opportunities for cross-selling our solutions, as well as the ability to further penetrate the massive retail and e-commerce industries."
Based on pre-determined profitability performance metrics over the next 12 months, the total maximum consideration for the transaction could reach $52.0 million.
"If completed, this accretive acquisition would mark a pivotal moment in GreenBox's history by adding over $500 million in processing volume to our Gen-3 platform and propelling us into the massive retail industry, as well as several other industries that we believe are ideally suited for our solutions," said Fredi Nisan, Chief Executive Officer of GreenBox POS. "By leveraging our stock, which was priced at a significant premium of $2.00 per share, we expect to deliver a significant amount of shareholder value in the immediate term while cross-selling services and moving into other high-value, high-margin markets. We look forward to working together with the entire ChargeSavvy team as our technologies work together to disrupt the entire payment solutions market as we know it."
About GreenBox POS
GreenBox POS (OTCQB:GRBX) is an emerging financial technology company leveraging proprietary blockchain security to build customized payment solutions. The Company's applications enable an end-to-end suite of turnkey financial products, reducing fraud and improving the efficiency of handling large-scale commercial processing volumes for its merchant clients globally. For more information, please visit the Company's website at www.greenboxpos.com.
About ChargeSavvy
ChargeSavvy is a global Fintech company focused on payment processing and software within the merchant services industry. The Company's proprietary point of sale product provides niche retail merchants an all-in-one solution to manage client transactions with added tools to protect against chargebacks and fraud. The company also offers e-commerce and delivery transactions software technology. For more information, please visit the company's website at www.chargesavvy.com to learn more.
https://irdirect.net/prviewer/release_only/id/4601434
I agree, this hold up of lenz is beyond ridiculous at this point. Get it out there to treat those suffering now!
See 10Q litigation.
Don't Mess with Texas!
The Defendants filed a Motion to Dismiss the Complaint in the Alliance Texas Holdings Case on July 24, 2020. The Parties completed briefing on the Motion to Dismiss on September 4, 2020. The Motion to Dismiss is currently being considered by the court.
iBio may be a viable solution for fast manufacturing. Their plant made pharmaceuticals factory is state of the art. I think a ex- Lonza exec. is at the helm. It's been a while since I followed the company.
Good News! A bit more info. on Barda and SNS:
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=158603406
I'm still holding long over there. It looks like we have two winners for science and treating patients in need.. Let's see how it all plays out. GLTU
Short interest:
Humanigen, Inc. - Common Stock
Settlement Date Short Interest Percent Change Average Daily Share Volume Days to Cover
10/15/2020 574,420 42.34 1,039,264 1.00
09/30/2020 403,554 100.00 676,441 1.00
It's a process of yes and no's
No P3 communication/completion
No EUA/rev. confirmation
yes chart gap @ 10.55
GLTA
Powerwalker: Great News for longtime longs!
Jay, so sorry to hear of your loss. That is a great story of love from above. My prayers go out to you, my friend.
lol. That's funny shit. good luck!
My new screen saver. Please update every increment of 5$ in gains. :)
We know better.
Azar, He also served as Vice President of Lilly’s U.S. Managed Health Care Services in 2009 and then President of Lilly USA, LLC in 2012.
Don't be surprised if you do not hear from him until after EUA. That is how it happened with CTSO. He had selective amnesia, lol.
Gotcha. Do you know if seeking IRB approval still applies? thanks