Anavex Life Sciences Corp (AVXL)

[roygbiv]

Plex,
Written by
The Political Economist profile picture
The Political Economist
I am the impassioned pundit at whyistherestillhunger.com. I have long studied and written about hunger, as...
495 Followers





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
495 Followers
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.
Show more
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.


Like (25)

Save

Share

Print
Comments (128)
Never miss the best dividend ideas!
Dividend Ideas Newsletter
221,163 subs.
Recommended For You
Clinically Sound Investor profile picture
Cassava Sciences' Data Once Again Misunderstood
Clinically Sound Investor
Victor Dergunov profile picture
The Rebound Is Coming, And It Could Be Epic
Victor Dergunov
Lane Simonian profile picture
Cassava Sciences And Alzheimer's Disease: Unravelling The Data
Lane Simonian
Avisol Capital Partners profile picture
Anavex: Despite Positive Spin, No Clarity On Anomalies
Avisol Capital Partners
Rida Morwa profile picture
2 Great Picks To Reach $2 Million In Retirement
Rida Morwa
Comments (128)
Sort by
Newest


G
georgejjl
04 Feb. 2023, 7:24 PM

Comments (286)
|
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,

Like
G
georgejjl
04 Feb. 2023, 6:27 PM

Comments (286)
|
Kun Jin
Vice President and Head of Biostatistics at Anavex Life Sciences
www.linkedin.com/...
EXCELLENT recent hire!!!
Good luck and GOD bless,

Like
C
cucumberbatch
04 Feb. 2023, 8:37 PM

Comments (3.72K)
|
@georgejjl EXCELLENT recent hire!!!
more like a bureaucrat cashing in on his insider contacts.

Like
G
georgejjl
Yesterday, 5:05 PM

Comments (286)
|
@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,

Like
The Political Economist profile picture
The Political Economist
02 Feb. 2023, 9:54 AM

Contributor
Premium
Comments (1.42K)
|
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.

Like
sparkmeister profile picture
sparkmeister
02 Feb. 2023, 12:24 PM

Comments (67)
|
@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.

Like
The Political Economist profile picture
The Political Economist
01 Feb. 2023, 4:03 PM

Contributor
Premium
Comments (1.42K)
|
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.

Like
S
s19104
01 Feb. 2023, 11:02 AM

Comments (140)
|
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.

Like
UP & DOWN profile picture
UP & DOWN
01 Feb. 2023, 11:51 AM

Premium
Comments (1.3K)
|
@s19104 Why didn't SAVA use Biomarkers in there most recent data release?

Like
S
s19104
01 Feb. 2023, 12:39 PM

Comments (140)
|
@up & DOWN They are going the more traditional route with2 large phase 3 studies in progress.

Like
UP & DOWN profile picture
UP & DOWN
01 Feb. 2023, 1:47 PM

Premium
Comments (1.3K)
|
@s19104 But no P value ....means no Stat Sig ! Seems more and more like the SAVA FUD machine ship is slowly sinking.

Like
The Political Economist profile picture
The Political Economist
31 Jan. 2023, 2:00 PM

Contributor
Premium
Comments (1.42K)
|
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.

Like
The Political Economist profile picture
The Political Economist
31 Jan. 2023, 1:59 PM

Contributor
Premium
Comments (1.42K)
|
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.

Like
B
badkindle46
31 Jan. 2023, 8:57 AM

Premium
Comments (2)
|
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.

Like
B
brad_scat
31 Jan. 2023, 1:20 PM

Comments (1.12K)
|
@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.

Like
sts66 profile picture
sts66
31 Jan. 2023, 4:04 PM

Comments (18.7K)
|
@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.

Like
C
cucumberbatch
31 Jan. 2023, 4:12 PM

Comments (3.72K)
|
@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.

Like
B
bufnyfan1
31 Jan. 2023, 8:16 AM

Comments (745)
|
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

Like
D
Davy Crockett
31 Jan. 2023, 11:41 AM

Premium
Comments (1.81K)
|
@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.

Like
E
earljr1
30 Jan. 2023, 11:11 PM

Marketplace
Comments (1.09K)
|
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?

Like
Sage Advisors profile picture
Sage Advisors
31 Jan. 2023, 8:36 AM

Contributor
Premium
Comments (860)
|
@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.

Like
The Political Economist profile picture
The Political Economist
31 Jan. 2023, 1:49 PM

Contributor
Premium
Comments (1.42K)
|
@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.

Like
C
cucumberbatch
31 Jan. 2023, 2:02 PM

Comments (3.72K)
|
@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?

Like
P
ponymon
30 Jan. 2023, 9:27 PM

Premium
Comments (65)
|
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/...

Like
User 6715991 profile picture
User 6715991
30 Jan. 2023, 6:23 PM

Comments (80)
|
Great analysis

Like
G
georgejjl
30 Jan. 2023, 5:26 PM

Comments (286)
|
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

Like
The Political Economist profile picture
The Political Economist
31 Jan. 2023, 1:50 PM

Contributor
Premium
Comments (1.42K)
|
@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.

Like
UP & DOWN profile picture
UP & DOWN
30 Jan. 2023, 4:53 PM

Premium
Comments (1.3K)
|
All the best to your investing success.
www.youtube.com/...

Like
W
winnnerwinnerchickendinner
30 Jan. 2023, 4:20 PM

Premium
Comments (278)
|
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?

Like
D
doctahJonez
30 Jan. 2023, 4:05 PM

Premium
Comments (419)
|
"Anavex will likely present and publish in a peer-reviewed journal the Phase 2b/3 data in Q1 2023." any source for this?

Like
D
doctahJonez
31 Jan. 2023, 8:13 PM

Premium
Comments (419)
|
@The Political Economist ?

Like
Sage Advisors profile picture
Sage Advisors
30 Jan. 2023, 3:54 PM

Contributor
Premium
Comments (860)
|
"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.

Like
rx7no1 profile picture
rx7no1
30 Jan. 2023, 5:42 PM

Comments (74)
|
@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.

Like
B
brad_scat
30 Jan. 2023, 10:38 PM

Comments (1.12K)
|
@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.

Like
C
cucumberbatch
30 Jan. 2023, 10:58 PM

Comments (3.72K)
|
@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'????

Like
The Political Economist profile picture
The Political Economist
30 Jan. 2023, 3:19 PM

Contributor
Premium
Comments (1.42K)
|
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.

Like
C
cucumberbatch
30 Jan. 2023, 3:44 PM

Comments (3.72K)
|
@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

Like
B
brad_scat
30 Jan. 2023, 10:40 PM

Comments (1.12K)
|
@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.

Like
C
cucumberbatch
30 Jan. 2023, 10:59 PM

Comments (3.72K)
|
@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.

Like
C
ConfirmationBiasSuxs
30 Jan. 2023, 3:14 PM

Premium
Comments (3)
|
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?

Like
The Political Economist profile picture
The Political Economist
31 Jan. 2023, 1:54 PM

Contributor
Premium
Comments (1.42K)
|
@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.

Like
sts66 profile picture
sts66
31 Jan. 2023, 3:42 PM

Comments (18.7K)
|
@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.

Like
smikhail profile picture
smikhail
30 Jan. 2023, 3:06 PM

Comments (3.35K)
|
@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?

Like
The Political Economist profile picture
The Political Economist
30 Jan. 2023, 3:22 PM

Contributor
Premium
Comments (1.42K)
|
@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.

Like
smikhail profile picture
smikhail
30 Jan. 2023, 5:12 PM

Comments (3.35K)
|
@The Political Economist
What about my first question regarding Rett syndrome approval?

Like
B
brad_scat
30 Jan. 2023, 10:40 PM

Comments (1.12K)
|
@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.

Like
Downtown10 profile picture
Downtown10
30 Jan. 2023, 3:05 PM

Premium
Comments (5.72K)
|
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.

Like
B
brad_scat
30 Jan. 2023, 10:36 PM

Comments (1.12K)
|
@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

Like
sparkmeister profile picture
sparkmeister
30 Jan. 2023, 11:43 PM

Comments (67)
|
@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.

Like
Downtown10 profile picture
Downtown10
30 Jan. 2023, 11:59 PM

Premium
Comments (5.72K)
|
@sparkmeister Hope you and @brad_scat are right!

Like
2959 profile picture
2959
30 Jan. 2023, 2:36 PM

Premium
Comments (1.08K)
|
Any thoughts on the comparison to the BIVI (BioVie) pipeline?

Like
The Political Economist profile picture
The Political Economist
30 Jan. 2023, 3:14 PM

Contributor
Premium
Comments (1.42K)
|
@2959 I am not familiar enough to give you an opinion. Didn't Lane Simonian write on BIVI and AVXL recently?

Like
Lane Simonian profile picture
Lane Simonian
30 Jan. 2023, 3:38 PM

Contributor
Premium
Comments (1.41K)
|
@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.

Like
2959 profile picture
2959
30 Jan. 2023, 3:41 PM

Premium
Comments (1.08K)
|
@Lane Simonian Thanks, I will look for it and add you to my follow list. Take care.

Like
Lane Simonian profile picture
Lane Simonian
30 Jan. 2023, 2:34 PM

Contributor
Premium
Comments (1.41K)
|
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.

Like
UP & DOWN profile picture
UP & DOWN
30 Jan. 2023, 4:59 PM

Premium
Comments (1.3K)
|
@Lane Simonian www.youtube.com/...

Like
Lane Simonian profile picture
Lane Simonian
30 Jan. 2023, 5:46 PM

Contributor
Premium
Comments (1.41K)
|
@up & DOWN Good work by Jesse as always.

Like
sts66 profile picture
sts66
31 Jan. 2023, 3:38 PM

Comments (18.7K)
|
@Lane Simonian Blarcamesine acts on a whopping 11 different brain functions/actions? I think you're missing the word "may" in that 2nd paragraph.......

Like
The Political Economist profile picture
The Political Economist
30 Jan. 2023, 2:20 PM

Contributor
Premium
Comments (1.42K)
|
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.

Like
Sage Advisors profile picture
Sage Advisors
30 Jan. 2023, 4:08 PM

Contributor
Premium
Comments (860)
|
@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.

Like
B
brad_scat
30 Jan. 2023, 10:35 PM

Comments (1.12K)
|
@Sage Advisors they didn’t have the full data. That is known and was clear.

Like
sparkmeister profile picture
sparkmeister
30 Jan. 2023, 11:05 PM

Comments (67)
|
@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.

Like
G
Goudadog
30 Jan. 2023, 2:06 PM

Premium
Marketplace
Comments (17)
|
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.

Like
The Political Economist profile picture
The Political Economist
30 Jan. 2023, 3:24 PM

Contributor
Premium
Comments (1.42K)
|
@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.

Like
rx7no1 profile picture
rx7no1
30 Jan. 2023, 5:56 PM

Comments (74)
|
@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!

Like
sts66 profile picture
sts66
31 Jan. 2023, 3:33 PM

Comments (18.7K)
|
@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.

Like
Small Pharma Analyst profile picture
Small Pharma Analyst
30 Jan. 2023, 1:41 PM

Contributor
Comments (1.06K)
|
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.

Like
The Political Economist profile picture
The Political Economist
30 Jan. 2023, 2:00 PM

Contributor
Premium
Comments (1.42K)
|
@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?

Like
rx7no1 profile picture
rx7no1
30 Jan. 2023, 5:59 PM

Comments (74)
|
@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.

Like
B
brad_scat
30 Jan. 2023, 10:35 PM

Comments (1.12K)
|
@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????????

Like
D
DawesR
30 Jan. 2023, 1:22 PM

Premium
Comments (6)
|
What is the estimated cost of treatment for Blarcamesine as compared to Leqembi?

Like
The Political Economist profile picture
The Political Economist
30 Jan. 2023, 2:01 PM

Contributor
Premium
Comments (1.42K)
|
@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.

Like
sts66 profile picture
sts66
31 Jan. 2023, 3:17 PM

Comments (18.7K)
|
@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).

Like
B
brad_scat
30 Jan. 2023, 1:08 PM

Comments (1.12K)
|
Indeed.

Like
S
Stockdoc96
30 Jan. 2023, 1:02 PM

Premium
Comments (350)
|
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).

Like
The Political Economist profile picture
The Political Economist
30 Jan. 2023, 1:49 PM

Contributor
Premium
Comments (1.42K)
|
@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.

Like
brichnyc profile picture
brichnyc
31 Jan. 2023, 8:29 AM

Comments (87)
|
@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.

Like
The Political Economist profile picture
The Political Economist
31 Jan. 2023, 11:15 AM

Contributor
Premium
Comments (1.42K)
|
@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.

Like
sierranvin profile picture
sierranvin
30 Jan. 2023, 12:41 PM

Comments (684)
|
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.

Like
C
Carlos54
30 Jan. 2023, 4:24 PM

Premium
Comments (974)
|
@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

Like
C
cucumberbatch
30 Jan. 2023, 5:13 PM

Comments (3.72K)
|
@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.

Like
sparkmeister profile picture
sparkmeister
30 Jan. 2023, 11:32 PM

Comments (67)
|
@sierranvin thankfully, there is TGA (AU) and EMA (EU) to provide first approvals this year, while the compromised FDA cleans egg off their faces.

Like
R
rbordogna378
30 Jan. 2023, 12:35 PM

Comments (241)
|
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.

Like
The Political Economist profile picture
The Political Economist
30 Jan. 2023, 12:37 PM

Contributor
Premium
Comments (1.42K)
|
@rbordogna378 thanks for the heads up. I will have to read that article!

Like
Downtown10 profile picture
Downtown10
30 Jan. 2023, 1:02 PM

Premium
Comments (5.72K)
|
@rbordogna378 Here is a link to the article: www.miamiherald.com/...

Like
R
Ronny1703
30 Jan. 2023, 12:33 PM

Comments (72)
|
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.

Like
The Political Economist profile picture
The Political Economist
30 Jan. 2023, 12:39 PM

Contributor
Premium
Comments (1.42K)
|
@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.

Like
The Political Economist profile picture
The Political Economist
30 Jan. 2023, 12:30 PM

Contributor
Premium
Comments (1.42K)
|
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.

Like
C
cucumberbatch
30 Jan. 2023, 1:18 PM

Comments (3.72K)
|
@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

Like
The Political Economist profile picture
The Political Economist
30 Jan. 2023, 1:43 PM

Contributor
Premium
Comments (1.42K)
|
@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.

Like
The Political Economist profile picture
The Political Economist
30 Jan. 2023, 1:45 PM

Contributor
Premium
Comments (1.42K)
|
@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).