This is the unhealthy information. And the excellent news. From at this time’s Anavex Life Sciences (NASDAQ:AVXL) convention name:
Now we have met the European Company a number of instances in conferences and we have now shared the information which isn’t but revealed, which is the revealed date of — the deliberate revealed communication of the total information of the Alzheimer Section 2b/3 examine. And we had been from this assembly beneficial to proceed with this software, full approval software. And that is what we proceeded with final week accordingly.
The excellent news is, after displaying the EU drug paperwork the Section 2b/3 full information set, the EU beneficial that Anavex “proceed with” a “full approval software.” This means that the EU sees the Section 2b/3 drug trial outcomes as ample not less than to decide on approving (or not approving) Blarcamesine.
And Anavex has already utilized to the EU for approval.
As mentioned in earlier articles, the drug appears to be like each extremely efficient and secure. One of many remaining questions was whether or not regulatory businesses worldwide would require Anavex to do any additional drug trials. The EU apparently doesn’t see this want. That is excellent news.
The unhealthy information. The EU is often deal slower than the U.S. FDA in its drug analysis and approval course of. It may take over a 12 months.
However, these regulatory businesses don’t work in a vacuum. They perceive the pressing want for a secure, efficient, reasonably priced Alzheimer’s drug, and that sufferers “want it yesterday,” so to talk. Would possibly the EU fast-track the one efficient Alzheimer’s pharmaceutical that doesn’t trigger mind bleeding (like Biogen’s Leqembi does)?
I feel so.
The U.S. FDA Accelerated Approval Course of
And what concerning the U.S. FDA?
Anavex had been making ready to use for Accelerated Approval by the FDA. This, from a earlier (Could 2023) quarterly convention name:
With newly obtainable preliminary efficacy outcomes of surrogate biomarkers, we contemplate initiating discussions with regulatory businesses for Accelerated Approval Pathway for ANAVEX2-73. In parallel, we plan to proceed with the initiation of our confirmatory Alzheimer’s illness examine.
Accelerated approval on the U.S. FDA requires {that a} drug display an impact on not less than one associated biomarker. Biogen’s Alzheimer’s drug, Leqembi, as an example, demonstrated an impact on amyloid plaques within the mind.
In a September press launch, Anavex said that Blarcamesine lowered the degrees of amyloid plaques within the mind. Moreover, Blarcamesine affected the last word Alzheimer’s biomarker: mind quantity. The drug slows the lack of mind quantity. Each findings had been statistically vital, with stopping mind loss being a consequence at a particularly excessive stage of statistical significance.
So, that appears to examine the biomarker field; all appears ready for accelerated approval, proper? Can they get accelerated approval with the biomarker information? How choosy is the FDA concerning accelerated approval for Alzheimer’s medication? From the Could convention name:
The subsequent query is, will the AD NDA be submitted earlier than the confirmatory trial is accomplished?
The reply is after dialogue with the company for Accelerated Approval Pathway, this could be the trail which was additionally given to the opposite accelerated approval firm approvals. So this could possibly be the case as nicely. In any other case, it could be not accelerated approval for those who want a examine to start with. So that’s the objective of getting the drug accredited earlier than finishing a confirmatory second trial.
Right here, CEO Missling repeats the objective of profitable accelerated approval WITHOUT having to do a “confirmatory second trial” which could take one other 12 months. Certainly, from what the general public has seen of their Section 2b/3 trials, the drug is simpler than Leqembi in slowing cognitive decline as measured by the ADAS-Cog13 and the CDR-SB. And Leqembi was granted accelerated approval, as Missling states within the above excerpt, so Blarcamesine ought to be granted the identical.
All is about, proper? The biomarker information appears to be like nice. Leqembi received accelerated approval with biomarker information alone. Get the applying into the FDA!
The U.S. FDA Common Approval Course of
The twist. Throughout the August convention name, CEO Missling dropped this bomb on us:
Now we have been heard from KOLs [Key Opinion Leaders] that really this extension examine [ATTENTION-AD] could possibly be the confirmatory examine of the ANAVEX2-73 Section 2/3 examine itself. So we wish to principally put this in context and see how this can progress. Accordingly, so we would have already got began this confirmatory examine with that open-label examine, however will probably be decided in dialogue with regulatory businesses. However we might, in fact, have the ability to, with out a downside, provoke a examine, in that case required, at any time.
Right here, CEO Missling says that Anavex may apply for the common approval course of utilizing the ATTENTION-AD OLE because the confirmatory examine. The accelerated approval doesn’t require a confirmatory examine.
This week’s quarterly convention name confirmed that Anavex would apply for FDA approval utilizing ATTENTION-AD as a part of the applying bundle:
Now we have the continued ATTENTION-AD examine ongoing and that is a part of the bundle of the applying with the Section 2b/3 examine.
Right here, Missling doesn’t specify whether or not he’s speaking about making use of for normal approval or accelerated approval. Considering the declarations of the previous three convention calls, Anavex seems to be making use of for BOTH accelerated approval AND common approval to market Blarcamesine for Alzheimer’s Illness within the USA.
Regardless of which path they take, the timeline for approval could also be about the identical.
Right here is the follow-up query to the August convention name excerpt from above:
Soumit Roy
I see. Do you’ve any date in thoughts when the FDA dialog may occur if this examine can translate right into a affirmation examine?
Christopher Missling
Sure. We’re planning to do that as soon as the information is obtainable, which is predicted this 12 months. And thereafter, company is ready to tackle issues with information as nicely. And that is what is going to occur with information, in presence of information.
Right here, the analyst Soumit Roy asks Missling when he’ll discover out if the ATTENTION-AD examine can rely as a confirmatory examine for the common approval software. Missling says that the “information” shall be obtainable in 2023. I assume which means that ATTENTION-AD shall be accomplished in 2023, which appears too early to me, contemplating the Section 2b/3 examine was apparently “accomplished” in “mid-2022” in line with a 10-Q submitting.
Regardless of the case, it’s on file that the CEO said that the “information” shall be “obtainable” in 2023, and that information, together with the applying to the U.S. FDA will transfer the inventory worth.
Inventory Worth and Timeline
Instantly after this week’s convention name, AVXL inventory tanked by about 10%. I’m not certain what sellers had been responding to, or if shorts introduced the inventory down.
Latest occasions, press releases, and declarations by the corporate point out that approval for a drug that may herald tens of billions of {dollars} a 12 months may come as early as spring 2024. AVXL has a market cap of about 500 million {dollars}.
It took solely about three months for the FDA to grant accelerated approval to Leqembi after it reported Section 3 outcomes.
That is what I think about Anavex will do: The corporate will put collectively the entire Section 2b/3 medical information together with Section 2b/3 biomarker information (which simply got here out two months in the past) together with ATTENTION-AD OLE information and hand it over to the FDA. It will symbolize 144 weeks of information for a whole bunch of sufferers, all of which could have taken the drug for between 96 and 144 weeks. Anavex will inform the FDA, “With all this information, please contemplate Blarcamesine for BOTH accelerated and for normal approval.”
I think about this information bomb will drop in early 2024, however I’ve been very improper earlier than about when information is dropped, so beware.
If I’m appropriate, FDA approval might happen as early as spring or summer time 2024.
The EU approval course of has already begun, and that call could also be made in 2024, maybe spring or summer time if the EU prioritizes its 7 million dementia sufferers.
With dementia care costing a whole bunch of billions of {dollars} in direct and oblique prices for EACH the EU and the USA yearly, approving Blarcamesine a month sooner than later may save tens of billions of {dollars} for the Western, democratic world. That is a significant productiveness enhance for economies with huge finances deficits burdened by elder-care.
Contemplating Leqembi prices $26,500 per affected person, plus 5 MRIs and 26 IV-infusion workplace visits every year, the H.C. Wainwright value goal introduced at this time of $54 per AVXL share appears conservative. Blarcamesine will undercut Leqembi on value and shall be far safer than Leqembi. No IV-infusions and no MRIs and no mind bleeding.
Most of all a slowing down of cognitive decline the likes of which has by no means been matched in any drug trial, in addition to the primary drug ever to display mind quantity preservation.
And even the shorts will agree, the tens of tens of millions of lives reworked is the best reward of all.
Addendum: Extra on the ATTENTION-AD OLE and the Parkinson’s Dementia OLE research
Excellent news concerning the ATTENTION-AD examine (from this week’s cc):
…we had extraordinarily excessive rollover from the double-blind, placebo-controlled [drug trial] into the open-label ATTENTION-AD examine. I feel it was over 90%. And we have now numerous sufferers on this examine. We even have the primary sufferers who completed that examine going over and requesting an extension of this extension by one other 12 months. So it turned now a 144 week examine for some sufferers. And thereafter, we even have sufferers which requested to be given the drug constantly, and we supplied them the drug on compassionate use. So there is a excessive request for sufferers to remain on the examine drug.
With 90% of the individuals from the 2b/3 trial (which noticed 508 individuals) persevering with on to the ATTENTION-AD OLE trial, plainly the individuals actually consider the drug is efficient. Additional, the massive variety of individuals might enable the OLE examine for use as a confirmatory examine.
A lot of these within the ATTENTION-AD examine have already accomplished the 96 weeks, so Anavex might have already got some clue as to how the drug carried out. The individuals themselves even have some concept, as they’ve all taken the drug for 22 months longer than earlier than. And it appears many have requested to increase their participation by one other 48 weeks or take the drug indefinitely out of compassionate use.
Should you take a look at the Parkinson’s Illness Dementia Section 2, placebo-controlled, double-blind, randomized drug trial of Blarcamesine, you will note large enchancment and slowing of decline amongst its individuals.
After which for those who take a look at the Parkinson’s Illness Dementia open-label extension examine, you will note that the impact of the drug didn’t disappear after the preliminary trial. Members steadily benefited from the drug throughout that OLE.
I count on the ATTENTION-AD OLE examine to display comparable results: continued constant helpful results of Blarcamesine. In reality, for the twenty sufferers that remained (even by means of Covid) for the complete 48 weeks of the Parkinson’s Dementia OLE, the common and the median scores really IMPROVED in 4 vital classes.
Lastly, Anavex has already performed a 260-week OLE of its Section 2a (not 2b) examine. This included a small variety of individuals. Security was good, and people taking bigger doses of Blarcamesine noticed larger profit from the drug. Aside from that, little could possibly be concluded by this small examine.
The Competitors’s OLE
Biogen didn’t have to incorporate the Leqembi OLE outcomes for his or her accelerated approval course of, and three OLE individuals died apparently on account of Leqembi’s brain-bleeding unwanted side effects. Cynically, which may be why the Leqembi OLE examine was not thought of by the FDA within the decision-making course of; they needed to shortly approve Leqembi with out having to reply questions on affected person deaths. The FDA, in any case, was discovered by a Congressional investigation, to have held secret, undocumented and unethical conferences with Biogen with a view to get their even much less efficient but additionally harmful Alzheimer’s drug, Aduhelm, accredited.
With three individuals dying from Leqembi of their extension examine, the FDA could also be extra within the security information from the 96-week Blarcamesine extension examine.
A kind of Leqembi deaths occurred after solely 6 weeks of Leqembi use throughout the extension examine; it isn’t clear if she had been within the placebo or the medicated arm of the unique Leqembi examine. The makers of Leqembi apparently didn’t reveal the dying of this girl (in in any other case good well being) at a significant convention presentation. Months later, Leqembi was granted accelerated approval by the FDA, which apparently knew about all three brain-bleeding deaths.
There have been no deaths attributable to Blarcamesine even after 5 years of use by OLE examine sufferers.