Does Anavex's Alzheimer's Drug Actually Confer Benefit?
May 15, 2025 8:49 PM ETAnavex Life Sciences Corp. (AVXL) StockBIIB, LLY, AVXL8 Comments
The Political Economist
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Anavex Life Sciences' OLE study demonstrates that its Alzheimer's drug works for years beyond the clinical study. The OLE expands efficacy to include patients' behavioral abilities.
The Anavex drug may offer years of extra mental lucidity and greater self-sufficiency among Alzheimer's patients.
The EU's approval of Blarcamesine could increase Anavex's market value from $800 million to $8 billion.
Mental health, jigsaw pieces, puzzle in brain shape on black background
akinbostanci/iStock via Getty Images
Last year, top researchers in Alzheimer's Disease treatments published a scientific journal article describing how a new drug can slow the cognitive decline of Alzheimer's patients by 36%, and by nearly 50% for people with a particular genotype. About 70% of humans have that particular genotype, so an enormous portion of the population would likely gain years of mental lucidity if they used this new drug.
The new drug is called Blarcamesine, and it was invented by Anavex Life Sciences (NASDAQ:AVXL). The European Medicines Agency has accepted Anavex's application to market Blarcamesine as a daily pill for Alzheimer's treatment. By the end of the year, Alzheimer's patients around the world will know if the EU has ushered in a new hope for them.
The Phase 2b/3 clinical trial demonstrated that taking Blarcamesine over the course of 48 weeks slows cognitive-behavioral decline by 27% as measured by the CDR-SB. This performance equals that of the leading FDA-approved drug: Biogen's Lecanemab.
Plus, Blarcamesine does not cause brain-bleeding, while Lecanemab does. And Blarcamesine took about thirty weeks less than Lecanemab to produce the impressive results.
And yet, for many whose family members suffer from Alzheimer's Disease, a lingering question remains. Would Blarcamesine work beyond the first 48 weeks of treatment? A prolonged effect could mean the difference between months of extra mental lucidity and years of extra mental lucidity.
An Open-Label Extension (OLE) study of Blarcamesine attempted to answer that question.
The OLE Study
The Open Label Extension Study for Anavex's Blarcamesine drug went on for 144 weeks. It started after the original 48-week, double-blind Phase 2b/3 clinical trial ended.
In an early April presentation at the AD/PDTM 2025 Conference in Vienna, Austria, Dr. Timo Grimmer presented the results in a paper entitled, "Phase IIb/III ATTENTION-AD Study: Over Three Years of Continuous Treatment with Oral Blarcamesine Continues to Significantly Benefit Early Alzheimer’s Disease Patients."
I agree that the OLE provided crucial evidence that Blarcamesine confers clinical benefits for three years or possibly close to four years.
Let me describe the OLE. Both the treatment group and the placebo group patients of the clinical trial were offered an opportunity to take Blarcamesine as a daily pill as part of the extension study.
The OLE patients were not unblinded, meaning, they were not told which group they belonged to in the original study -- the placebo group or the treatment group. This means that the patients could not draw any definitive conclusions about whether the drug had an effect on them in the original drug trial. In this way, a proper comparison could be made between the two groups in the OLE study.
The OLE compared two groups: the early starters (the group who had taken the drug during the clinical trial) and the late starters (the former placebo group, who started taking the drug only at the start of the OLE).
How will the rate of cognitive decline of the early starters compare to that of the late starters after 144 weeks? Will the late starters "catch up" to the early starters in their cognitive abilities?
And can any conclusions be drawn about the performance of the drug in slowing cognitive decline in general?
Better to Start Taking Blarcamesine Earlier than Later
All participants of the original clinical trial were composed of people diagnosed with Alzheimer's Disease. They were in the earlier stages of disease progression -- some suffered from Mild Cognitive Impairment (MCI) and some from Mild Dementia due to Alzheimer's. Among the trial participants there were a disproportionate number of people who carry the APOE4 gene, a gene variant that causes earlier and more severe Alzheimer's symptoms.
Anavex reported that the early starters declined cognitively at a slower pace than the late starters. The benefit of starting just 48 weeks earlier on Blarcamesine was rather great.
All of the findings were statistically significant at 192 weeks (the end of the study). The original study found that use of Blarcamesine slowed cognitive decline as measured by the ADAS-Cog13 by 36% over the course of 48 weeks. Of course, slowing decline by such a degree was extremely encouraging. The fact that the originally medicated patients widened its cognitive "lead" over the original placebo group over the course of an additional 144 weeks is meaningful.
Exactly how meaningful?
In the original clinical trial, the treatment group scored over 2 points "better" (a lower score) than the placebo on the ADAS-Cog13. That was after 48 weeks of treatment for the treatment group and 48 weeks of a placebo for the placebo group.
Then, during the OLE, both groups were treated daily with Blarcamesine. After an additional 144 weeks, the early starters extended their "lead" from 2.0 points to 3.83 points over the late starters. Even though the late starters had been treated for 144 weeks, the early starters nearly doubled their original "lead" over the late starters. The late starters not only did not catch up to the early starters, but they actually fell behind much further.
Anavex described the results in this manner:
The delayed-start analysis for ADAS-Cog13 showed a significant difference between early start and late start treatment groups up to Week 192 (LS mean difference -3.83, P = 0.0165), favoring the early start group. Together these results suggest that participants who initiated treatment with blarcamesine earlier in their disease progression showed greater stability of cognitive function compared to those who did not initiate blarcamesine until ~1 year later.
To put it another way, the group of patients who took Blarcamesine for 192 weeks scored a good deal better on the ADAS-Cog13 than the group of patients who took Blarcamesine for only 144 weeks. This way of looking at it makes it sound like taking Blarcamesine for just 48 weeks longer makes a huge difference. And that may very well be true.
It may also be true that taking Blarcamesine 48 weeks earlier in one's disease progression is of vast importance. That is the conclusion that Anavex drew from the OLE study, except without the "vast" descriptor.
What is very interesting is that the graph in Anavex's presentation shows that the late starters did indeed "catch up" to the early starters at "Week 96" on the graph (Week 48 of the OLE). So, after just 48 weeks of treatment during the OLE, the late-starters were approximately equal to the early-starters in their ADAS-Cog13 scores, despite the late starters having taken the drug for 48 weeks fewer than the early starters. What does this mean? It might mean that the first 48 weeks of treatment are quite powerful and that the second 48 weeks of treatment are not as powerful.
Over the next 96 weeks (Week 96 to Week 192 on the graph), the early starters pulled ahead by a great deal, speeding nearly 4 points "ahead" of the late-starters on the ADAS-Cog13 scores.
Interestingly, there was a subset of patients who had a much smaller delay between the original trial study and the OLE, specifically less than 19 days. This group, which enjoyed almost continuous access to Blarcamesine, actually sped ahead to a 4.2 point lead over the late-starters. So, those who had little or no interruption in their treatment opened up a 4.2 point lead over the late-starters, versus a 3.8 point lead for the entire group of early-starters. This indicates that uninterrupted intake of Blarcamesine has benefits over interrupting one's intake of the drug. To characterize the degree of the "lead," those who took Blarcamesine with little or no interruption more than doubled their already-large lead over the late starters.
All of the above-mentioned findings further demonstrate the efficacy of Blarcamesine to slow cognitive decline.
ADCS-ADL Results
The participants in the original trial took the ADCS-ADL test to measure their behavioral habits -- how well were they taking care of themselves and doing daily activities. The ADCS is based on caretaker interviews.
In the placebo-controlled original trial, the treatment group slowed their behavioral deterioration by 0.775 points compared to the placebo group. This 10% slowing of behavioral decline was not statistically significant. However, during the OLE, this 0.775 point "lead" that the treatment group held over the placebo group ballooned to 4.3 points. This was statistically significant, and represents a 5.5X multiplication of the original "gap" of .775 points.
For those who suffered little or no interruption in treatment, the multiple was 7.4X! The gap or "lead" was 5.75 points. To give some context, the original placebo group deteriorated by over 7.5 points during the 48-week clinical trial, and the treatment group deteriorated by over 6.7 points during that period. So, the gap that opened up between the two groups over 196 weeks (5.75 points) represents a major slowdown in behavioral decline for the early starters. It represents something like a 9-month delay in behavioral decline for the late-starters.
For further context, a typical Alzheimer's patient loses about 4 points per year on the ADCS-ADL, according to one journal article.
The weak spot of the original clinical study was the ADCS-ADL. Blarcamesine performed extremely well in slowing cognitive decline as measured by the ADAS-Cog13 and performed very well in slowing cognitive-behavioral decline as measured by the CDR-SB. But, like I said above, the drug did not show a statistically significant effect on a purely behavioral scale as measured by the ADCS-ADL.
The OLE shows with excellent statistical significance that the drug, taken earlier, produces a substantial effect in slowing behavioral deterioration, when compared to those who take the drug later. A not-unblinded OLE is not as good as the gold-standard placebo-controlled study, but the OLE results have strong statistical significance. And one of the top Alzheimer's researchers, Dr. Timo Grimmer, asserts that this demonstrates that taking Blarcamesine at the MCI/Early Alzheimer's stage slows behavioral deterioration.
On a practical level, taking Blarcamesine for four years may buy Alzheimer's patients an extra year of being able to cook, dress, or take a walk by themselves. And, based on the ADAS-Cog13, it looks like Blarcamesine taken early and over 196 weeks might enable a patient to remember their family members, friends, and homes for an extra year or two. These are estimations on my part.
Normal Rate of Decline Vs. OLE Patients' Rate of Decline
To give you an example as to how quickly AD patients' cognitive decline can accelerate, examine Graph D of this important study regarding the cognitive decline of Alzheimer's patients as measured by the ADAS-Cog13. The researchers followed two groups of patients: one "preclinical" group and another, worse-off group suffering from MCI. For our purposes, we are interested in patients who had an ADAS-Cog13 score of between 25 and 35, which would represent the patient population of the original Blarcamesine clinical trial.
It can easily take 18 years for a patient to advance from "preclinical" Alzheimer's Disease to Mild Cognitive Impairment (MCI) due to Alzheimer's and a score of 30 on the ADAS-Cog13; see Graph C. But once reaching an ADAS-Cog13 score of 30, a typical group of Alzheimer's patients tends to suffer a tremendous acceleration in their cognitive decline.
NOTE: the worse one's cognition, the higher one scores on the ADAS-Cog13, and the scale ranges from 0 to 85.
On Graph D, in Year 10 on the X-axis, we see that the 14 worst-performing patients on the ADAS-Cog13 were suffering from MCI and all 14 of them scored between 25 and 35 on the ADAS-Cog13; these 14 patients can serve as a stand-in for the patients in the Blarcamesine study. The patients in the Blarcamesine trial had an average ADAS-Cog13 score of about 30. In Year 13, just three years later, the 8 worst-off patients scored between 50 and 70 on the ADAS-Cog13; the next 6 worst-off patients score between 30 and 40. So you can see that cognitive decline can accelerate severely when patients reach the 25 to 35 range on the ADAS-Cog13. My point? We should see significant acceleration of cognitive decline for a group of patients scoring around 30 on the ADAS-Cog13.
The question, then, is, did the placebo patients in the clinical trial accelerate their cognitive decline over the course of the 144-week OLE study, as one might expect if Blarcamesine was ineffective?
Blarcamesine Slows Cognitive Decline For Three Years
Seeking Alpha scientist-writer Dr. C.C. Abbott proposed that though there was no placebo group for the OLE, we could use the original placebo group's clinical trial performance as a stand-in for a placebo group's would-be performance. In the original clinical trial, the placebo group worsened by over 5.58 points on the ADAS-Cog13 while the treatment group only worsened by 3.555 points; hence, the 2.0 point gap cited to prove efficacy for Blarcamesine.
Now let's examine the performance of the placebo group, now known as the late-starters, from Week 48 to Week 196 of the OLE. At Week 48 of the original study the placebo group had slid 5.582 points on the ADAS-Cog13. At Week 196, these late-starters had taken Blarcamesine for 144 Weeks, and their ADAS-Cog13 scores were about 20 points lower than baseline, or about 14.4 points worse than at the end of the clinical trial.
That means that over the course of 144 weeks of the OLE, they deteriorated at an average rate of 4.806 points every 48 weeks. Compare this rate -- 4.806 -- to the rate of decline during the clinical trial -- 5.582. The rate of cognitive decline had slowed by 13.890% after taking Blarcamesine, compared to the first 48 weeks. Imagine an Alzheimer's patient slowing their cognitive decline by nearly 14% each year for three years. The accumulated preservation of brainpower would be tremendous.
So, this is evidence, according to C.C. Abbott's methods, that Blarcamesine is indeed effective over the course of three years!
Now, there is a problem with C.C. Abbott's method. The first 48 weeks cannot serve as a proper stand-in for a placebo group for the late-starters because these patients, who started at about a 30 on the ADAS-Cog13 and then declined to a score of about 35 at the end of the clinical trial, should be accelerating their decline at this point in the disease progression. Meaning, these patients should be declining at a rate significantly greater than 5.582 points per 48 weeks.
So, let's say, without medication or placebo, they would have declined by 7 points per 48 weeks. Then what we see is that Blarcamesine is blowing open an enormous gap between the late-starters and our "would-be" stand-in placebo group. Declining 4.8 points as opposed to 7.0 points per 48 weeks means that Blarcamesine is slowing cognitive decline by 2.2 points per 48 weeks, similar to the findings of the clinical trial. These results from a safe, daily pill, if true, would be simply revolutionary.
IMPORTANT NOTE: The 20 point deterioration over 196 weeks I mentioned above was not a precise number supplied by Anavex. I had to blow up Graph 1 on page 19 of their presentation and use a virtual ruler to see where exactly the late-starters scored on the ADAS-Cog13 at Week 196. And that turned out be 20.0. It may be 19.9 or it may be 20.1. Neither of those levels would change my ultimate conclusions.
The Original Treatment Group
And how did the original treatment group perform over the course of the OLE? Again, by blowing up the image of Graph 1 on Page 19 of the presentation, I estimated that the treatment group had deteriorated by a total of approximately 16.1 points to 16.2 points. If you assume they deteriorated by 16.2 points, it would mean that the original treatment group deteriorated by a total of 12.645 points over the course of the 144 weeks of the OLE. That averages out to 4.215 points per 48-week period. This indicates that the original treatment group accelerated their rate of decline during the 144 weeks of treatment following the 48 weeks of the original trial. They accelerated their decline by 18.565%, which is unfortunate.
But if we compare that 4.215 point deterioration against the 5.582 point deterioration of the placebo group during the original trial, then this early-starter group is maintaining a major advantage. They are declining, even in these later stages of disease, at a 24.489% slower pace. Even as their decline accelerates, the early starters enjoy a nearly 25% slower rate of decline compared to a "would-be" placebo pace.
The fact that the treatment group, while continuing treatment, accelerated in their decline is not surprising, even if assuming that Blarcamesine works. After all, their disease stage and ADAS-Cog13 score indicate that their decline was due to accelerate. But because their rate of decline at about 4.2 points per 48 weeks was extremely slow relative to an expected rate of 5.5 or even 7 points per 48 weeks, it seems Blarcamesine continues to confer benefit up to nearly 4 years of treatment. All of this occurred even as some patients in this group likely descended into moderate Alzheimer's, a terrible stage of the disease where patients "fall off a cliff" in their cognitive abilities.
Three Years of Behavioral Benefits from Blarcamesine
The ADCS-ADL test measures the behavioral performance of Alzheimer's patients. The lower the score, the worse the patient is performing.
The placebo/late-starter group declined by 7.560 points in their behavior as measured by the ADCS-ADL in the 48 weeks of the original clinical trial. Over the course of the entire 196 weeks, this group declined by about 27.7 points on the ADCS-ADL. On average, over the course of the latter 144 weeks, constituting the OLE, the late-starters declined 6.71 points per 48-week period. So, it could be said that the late starters slowed their behavioral decline by over 11%, using the first 48 weeks as a would-be placebo.
The early start group saw a decline in their behavior of 6.785 points on the ADCS-ADL scale in the 48 weeks of the original trial. Over the following 144 weeks, the early starters saw a total decline of approximately 15.2 points. Again, I am using an online ruler to estimate this. The average loss of behavioral skills was about 5.066 points per 48-week period during the OLE. I conclude that the rate of decline during the latter 144 weeks was significantly slower than in the original 48 weeks, as measured by points on the ADCS-ADL. In fact, behavioral decline was 25.335% slower during the 144 weeks of the OLE than in the 48 weeks of the clinical trial. This is extremely encouraging!
Why did Blarcamesine seem to work better in Year 2, Year 3, and Year 4? It may be because by Year 2, the titration period had long ended, and patients no longer suffered the side effect of dizziness. After 48 weeks of taking the medication, their bodies may have adapted to Blarcamesine's side effects, and they may have learned to better deal with them mentally too.
Another theory is this. Blarcamesine effected a major deceleration in cognitive decline. This slower cognitive decline eventually slowed their decline in behavior too. However, this follow-on effect took time to be realized. After the initial year of medication, the behavioral benefits began to shine.
When the performance of the early starters during the OLE is compared to the rate of decline in the original placebo group during the clinical trial, we see a 33.000% slowing of behavioral decline. This, of course, is astounding, if it is true.
For those who experienced at most a short interruption in treatment (19 days or less), the average behavioral decline per 48-week period was only 4.5833 points. This represents a 32.450% slower decline in behavior than the rate of the treatment group in the initial 48-week study. And it represents a 39.374% slower decline in behavior from the placebo arm's decline rate in the first 48 weeks.
The slowing of behavioral decline and the slowing of cognitive decline are both quite amazing if they are indeed true and real.
The EU should organize another study of Blarcamesine's long-term efficacy, but it should allow ten million Alzheimer's patients to participate.
Market value of Blarcamesine
Of course, our family would have liked to have had access to Blarcamesine 192 weeks ago or even 48 weeks ago.
Families struggling with Alzheimer's Disease are ready to buy any pharmaceutical that has proven to work and has no serious side effects.
What are people willing to pay? Caring for someone with Alzheimer's Disease can cost in the $10,000s. For every year that that person can take care of themselves, the family may save that sum, plus maintain their own employment.
So, $10,000 a year would be a pretty low price tag for both the family and for the government. The EU spends about $30 billion on Alzheimer's patients a year.
The EU is home to 7 or 8 million AD patients. If the EU were willing to spend $10,000 each for 3 million AD patients annually, that amounts to a $30 billion price tag, translating to $30 billion or so in revenues for Anavex Life Sciences.
Is there price elasticity for an AD drug? Let's say the price tag is only $5000, and it's purchased for 8 million AD patients. That produces a $40 billion annual revenue stream.
The company is currently valued at about $800 million. Without product price information, I would expect the value of the company to increase immediately to between $8 billion and $16 billion, if and when the EU approves Blarcamesine for the treatment of people with MCI or early-stage dementia as a result of Alzheimer's Disease.
If the EU approves Blarcamesine for only a specific, smaller population as it has for Lecanemab, then, of course, the total annual revenue shrinks, but the global market would still be enormous.
If the EU rejects Blarcamesine outright, then the company may look for other avenues for drug approval, such as in the United States, Australia, or East Asian nations. But in that case, I foresee an immediate steep drop in stock value. I don't know where it would drop to; it would likely depend on what the EU stated exactly in its rejection. For instance, the EU rejected Lecanemab based on its brain-bleeding dangers to Alzheimer's patients. Biogen appealed the initial EU rejection and was able to win approval for Lecanemab for a smaller patient population.
If only one nation approves the drug, say, for instance, China, then it would likely attract millions of Alzheimer's families to buy the drug either in China, or through mail-order. In fact, China has made medical tourism, especially on the island of Hainan, a highly profitable industry in that nation.
If the drug were approved by Mexico, expect a lower price point and millions of people flocking to Mexico for Blarcamesine.
If the drug is rejected worldwide, the company could still carry on with some drug studies for its two candidates, but the stock price would plummet, and the company would be on the clock with its four-year cash-burn runway.
In that case, a larger company may buy Anavex out to see what they can do with Blarcamesine. Dr. Christopher Missling, the CEO of Blarcamesine, has mentioned on several occasions that Blarcamesine could be taken in tandem with infusions of Lecanemab.
Blarcamesine would fit neatly among Biogen's array of neurological treatments for dementia and MS. Dr. Missling hinted that the two drugs may produce a combined effect on slowing cognitive decline among those suffering from MCI or early Alzheimer's. Each drug slowed cognitive-behavioral decline by 27% as measured by the CDR-SB; Blarcamesine did it much faster and more safely.
Dr. Missling also seemed to hint that using the drugs together might produce a synergistic effect, as each drug works on a different facet of the disease.
Eli Lilly boasts a market cap of nearly $700 billion. Like Biogen, it has an antibody-based Alzheimer's drug called Kisunla, which slowed cognitive-behavioral decline by 29% on the CDR-SB over the course of 76 weeks (similar time frame as Lecanemab). Eli Lilly could buy out Anavex with no strain to its budget.
Lecanemab and Kisunla together killed about five patients during their drug trials due to the aforementioned brain bleeding side effects, as they both function in the same manner, draining amyloid plaques from the brain. (The patient liaison I spoke with could not or would not tell me exactly how many people died while taking Lecanemab during its drug trials)
Perhaps a combination therapy with Blarcamesine could allow for lower doses of these brain-bleeding drugs and mitigate the brain bleeding. This is pure speculation, but based on the fact that Blarcamesine manipulates autophagy, the brain's own chemical self-regulatory system. If Blarcamesine can help the brain produce fewer amyloid plaques and tau tangles, then there will be less need for amyloid-clearing drugs.
Sadly, families suffering from Alzheimer's have few options and if, say, a Chinese company stole or licensed the Blarcamesine formula and synthesized it at scale, it could probably make a fortune selling pills without any government marketing approval. The results of the Phase 2, Phase 2b/3, and multiple OLEs are so impressive, I would buy unapproved Blarcamesine for my mother who is at the moderate Alzheimer's stage now. And I would buy some for myself.
This type of fantasizing may not be necessary, as the EU approves the vast majority of drugs for which it accepts applications.
RISKS to owning AVXL stock
Anavex has only one drug that has ever been considered for approval by a regulatory agency. With each quarter, that Blarcamesine has not yet begun to generate revenues, the company loses millions of dollars. In the recently reported Q1 results, the company reported a loss of over $12 million and held nearly $121 million in cash and cash equivalents. The company spent over $10 million in R&D.
The press release stated that "As of quarter end, the Company anticipates, at current cash utilization rates and ranges, a runway of approximately 4 years."
If Anavex's Blarcamesine application is rejected by the EU, the stock price will plummet; this may happen later this year. It's not clear where it would drop to -- it would depend on if any progress was being made in applying to other regulatory bodies like the FDA or the Australian drug agency.
In the recent earnings call, the CEO Christopher Missling would not clue listeners in on exactly the progress they have made in their discussions with the FDA and other drug regulators.
An outside risk would involve a patient overdosing on Blarcamesine, or a patient becoming confused and suffering an accident and this being blamed on Blarcamesine. Sarepta's (SRPT) stock value was chopped nearly in half this year by one patient's death.
Other Drug Applications and Near-Term Catalysts
Anavex is working with J.P. Morgan to partner with a larger company in Europe to market Blarcamesine, as discussed in the recent earnings call. If an announcement is made that a large pharma company has partnered with Anavex, the stock price will spike. This could happen in weeks or months.
Blarcamesine has a great deal of potential as a treatment for Parkinson's Disease, as demonstrated by a Phase 2 double-blind, placebo-controlled trial. In fact, the results of the study were so stunning that Blarcamesine may prove even more effective at treating Parkinson's than Alzheimer's. Those in the Parkinson's Phase 2 study also participated in an OLE study. And much like the participants in the Alzheimer's OLE, those who suffered through a delay in treatment saw their Parkinson's symptoms worsen; when the drug was re-administered, the patients recovered gains they had lost during the interruption (due to Covid).
When the Parkinson's Phase 3 trial is completed, in 2026 at the earliest, it may provide an enormous catalyst for the stock price.
The company has one other molecule that is being tested in a tiny, early trial for people suffering from Schizophrenia. Results will be reported in H2. However, if the second drug candidate proves promising, it may put a stronger floor under the stock price in case Blarcamesine is rejected by the EU.
Conclusion
This is a classic binary situation with massive implications on the stock price and the fate of Anavex Life Sciences. If the EU approves Blarcamesine as a treatment for Alzheimer's Disease, the value of the stock will multiply by some whole-number factor.
If the EU rejects the drug, then the stock will be cut down.
The current valuation of the company leans heavily toward the "failure" end of the see-saw.
One may try to divine the drug's fate by carefully studying the Phase 2b/3 trial and the OLE study of Blarcamesine. But ultimately, the EU will make the decision, based on their own biases and ethical standards.
My bet is on approval, based on the results of the trials and based on the extreme need for a safe, effective brake on the brain-consuming machine called Alzheimer's Disease.
Addendum 1: More Evidence for the Acceleration of Symptoms from Preclinical to MCI to Early AD to Moderate AD
Those patients who participated in the original Blarcamesine clinical study were all originally in two categories: MCI and mild dementia due to AD. Some of those who started out in MCI likely descended into mild dementia during the study and some larger portion likely descended from mild dementia into moderate dementia due to AD.
One would expect many or most of these patients to accelerate their cognitive decline during a 192-week period, a period of almost four years.
This study published in Nature documents that the slope of change on the ADAS-Cog13 steepens between the time one is diagnosed with MCI and when one has entered mild dementia due to Alzheimer's Disease. That is to say, the worsening of symptoms accelerates from Preclinical to MCI to Mild Dementia (Early AD).
Furthermore, according to another study, disease progression (worsening of cognition and behavior) accelerates when a patient degenerates from MCI or mild dementia due to Alzheimer's into moderate dementia due to Alzheimer's Disease.
"Participants with MCI or mild dementia due to AD, compared to participants with moderate dementia due to AD, had numerically higher baseline iADRS scores and slower progression on the iADRS, the ADAS-Cog13, and ADCS-iADL."
This study actually used test scores attained from the placebo branches of several Alzheimer's drug trials.
Addendum 2: ADCS-ADL vs. ADCS-ADL MCI
Anavex's Blarcamesine and Biogen's Lecanemab cannot really be compared directly based on their ADCS-ADL score results. Biogen specifically aimed their drug trial at patients who were less debilitated. The Biogen Lecanemab patients at baseline scored 22% better on the CDR-SB scale of cognitive-behavioral function than the Blarcamesine trial patients.
The patients in the Anavex study were suffering worse symptoms and were further along in disease progression.
In fact, I even question whether some of the patients in the Biogen Lecanemab study had Alzheimer's Disease, specifically the patients with extremely low levels of tau tangles in their brain. Biogen and Eli Lilly both brag about how well their drugs work on people with low levels of tau. That's not surprising since these patients started their studies with far fewer of the chemicals that cause Alzheimer's Disease.
Because Biogen's Lecanemab patients suffered from less cognitive impairment, they took the ADCS-ADL MCI test rather than the ADCS-ADL test. The MCI stands for Mild Cognitive Impairment. This means that it was meant for people with MCI rather than for people who had progressed to early Alzheimer's Disease. This is appropriate, as the MCI test is likely far more sensitive as a measure, for people who are entirely in the MCI stage. The Blarcamesine patients were in both the MCI and the Early Dementia due to Alzheimer's stages.
Addendum 3: Regarding Dr. Timo Grimmer
Dr. Timo Grimmer was the primary author and presenter of the Blarcamesine OLE research. He is highly respected worldwide for his research into Alzheimer's Disease. The presentation included this disclaimer:
Dr. Grimmer received [or is] receiving consulting fees from Acumen, Advantage Ther., Alector, Anavex, Biogen, BMS; Cogthera, Eisai, Eli Lilly, Functional Neuromod., Grifols, Janssen, Neurimmune, Noselab, Novo Nordisk, Roche Diagnostics, and Roche Pharma; lecture fees from Cogthera, Eisai, Eli Lilly, FEO, Grifols, Pfizer, Roche Pharma, Schwabe, and Synlab; and has received grants to his institution from Biogen and Eisai.
This list helps us understand just how well-respected and powerful Dr. Grimmer is in the field of biopharmaceutical treatments for Alzheimer's. He has conducted research for major Alzheimer's treatment competitors such as Biogen, Eisai, and Eli Lilly. Most of these companies are many times larger than Anavex, and yet, Dr. Grimmer is deeply involved in an Alzheimer's drug invented by a tiny pharmaceutical company.
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