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OK, I was responding to a post about what I thought was your uncertainty on accelerated assessment at the EMA rather than the FDA.
Actually, if you look at the dates to begin the rapporteur process month by month, the actual selection is actually closer to 6 weeks after the submission deadline. Presumably because of the holidays, there seems to no submission deadline (and therefore commencement of the process) in the month of December.
frrol, according to the most recent (monthly) list, donanemab was not granted accelerated accelerated assessment. Its evaluation started on 8/17/23.
Thanks, Hosai. Perhaps because I am also a Gemini?
My understanding is that the second gating factor is when the company files for the rapporteurs. It won't get worked on until 7 months before the targeted MAA date. The EMA also advises against filing for the rapporteurs much later than 7 months prior. If the company also filed that in early/mid-December, then it would have met the January 10th submission deadline for the rapporteur process. It means that when Missling said on March 4th that he hadn't been notified yet on the rapporteur(s), the EMA had waited more than 6 or 7 business days after the published selection days to advise him of the outcome. Certainly possible, but it could also be that the company filed prior to the February 7th deadline (and they would have then been in the process, as Missling said, but were not going to be notified until after March 21st.) So, it seems to me, depending on our interpretation of Missling's comment, that the 7 month minimum until filing for the MAA would mean early/mid July to early September (at the very latest) for the MAA target given to the EMA, assuming the company does prepare it expeditiously, as you say. While mid-June is not inconceivable, I suppose, it seems quite unlikely with only three months left to work with the rapporteurs. I just prefer to expect Q3, leaning toward the first two months.
Baltimore, I have not heard of any new timeline given by the company on the MAA filing beyond the original "as early as possible in 2024." We do know, however, that when the company formally requested the appointment of rapporteurs on (or as much as 4 weeks before) February 7th, they had informed the EMA that the planned MAA submission date was prior to September 7, 2024. We know this because the company had to have an MAA submission date no more than 7 months later before the EMA would initiate the rapporteur selection process. On March 4 (at TD Cowen) Missling told us that he was awaiting notification of the rapporteurs and said that they were in the rapporteur selection process. The most recent filing deadline for the process at that time was February 7. I suppose since he said that they were awaiting notification, they could have met the January 10 deadline and that 6-7 business days after the selection process was theoretically over, the specific notification had not yet been given. I tend to go with February 7, but either way the target for submission was Q3 at that time.
plexrec, our CEO is playing by the pre-submission rules of the EMA, which he must. There are certain timing requirements that has to abide by. You can look it up, as Casey Stengel used to say. From what we have seen of the process so far we can safely say that he has given the EMA a projected filing date for the MAA in calendar Q3 of this year (and more likely in the first month or two).
Actually, Talon, Biogen is holding below $200 because of - not despite - Leqembi. The drug is falling well below sales projections. There are a variety of reasons, of course: physicians are, not surprisingly, quite leery about the possible side effects from a drug that is the first one with a black-box warning to be granted full approval by the FDA in two decades; infusion center capacities also seem to be a problem; getting PET scans signed off by private Medicare Advantage plans is another issue; approval by the EMA has been held up for further review, since the previously cited issues would seem to be even more of a problem in Europe; and Biogen/Eisai have been forced to delay an application for an injectable version after the FDA asked for several more months of immune response data. So, yes, Leqembi is doing no favors for BIIB shareholders.
He remains so.
It was a date in the summer of 2024 that Anavex told the EMA for submission of the MAA, and the EMA does not like to be disappointed on timing.
I found it quite worthwhile.
Fine summary thoughts on the Needham presentation, tschussmann. I, too, noticed the comment on the potential impact of 2-73 on aging. In the past Missling has commented on the potential prophylactic benefits of both 2-73 and 3-71 (presumably through the autophagy process), and I heard him once musing about that effect being something like taking a vitamin. However, I don't ever recall him specifically dropping the anti-aging suggestion. He tries not to be careless with words, and I suspect (like falconer long has) that the company has done clinical research on animals in that regard. Furthermore, since he let out that hint, I would imagine that the results were positive.
Frrol, I would agree that another phase 3 trial for Rett seems more likely than not, and I don't think Missling suggested differently in the last conference call.
However, while we indeed "have to contend with the endpoints' ostensibly successful use by other biotechs," it is worth pointing out that although the trial conducted by Acadia for DAYBUE - presumptively now the SOC - was fully blinded by clinical definition, the closely knit Rett community of parents makes extensive use of social media to share their experiences. The side effect of significant gastric distress (which afflicted over 80% of the patients and caused as many as half to drop out [as I recall]) did not go unreported on social media, thus de facto allowing for some real world unblinding by allowing parents of those who received the placebo to correctly imagine that their child was not receiving the drug.
It is also quite likely that the side effects are causing the rather tepid reception of DAYBUE in the marketplace and the somewhat disappointing subscription renewals. In their Q4 conference call in February Acadia (ACAD) gave revenue guidance for the quarter just ended that was about 15% lower than analyst estimates. The company cited "seasonal effects" from fewer patient office visits in January and early February. One analyst noted that patients taking DAYBUE had dropped from 900 at the end of the year to roughly 860 in late February. The stock fell sharply on the news.
Whether these things help Missling enough in his uphill battle to short circuit the requirement to redo a phase 3 remains to be seen, but they don't hurt.
Correct me if I am wrong, Joseph, but this article "From Autism to Alzheimer's..." seems to be recent (i.e., last week) rather than five years ago. Assuming it is, this is a new support structure for Anavex' case on the MOA. I suspect it will be extremely interesting and useful fodder to be presented with their applications at the EMA and FDA.
No, as far as the impact of an accepted EMA filing goes, you will be wrong. That event will trigger increased sell side coverage and increased ownership by institutions that can accommodate small cap stocks. With rather strong odds that the the EMA will approved, the stock will trade well in excess of $1 billion in market cap within a month or two of that.
Steady, mentioning as you did at the end of your post the long awaited PD trial, my last communication with an executive at the Shake It Up Australia Foundation about a month ago confirmed that they are still fully expecting that trial to commence this year. While the person said they were encouraging patients interested in this trial (or others, I'm sure) to register on their website so they will be available for recruitment when the trial is about to begin, I don't really take that statement to mean the trial is imminent.
Thanks for sharing your thoughts and experience with monoclonal antibodies, sab, and know that our thoughts are with you in your struggle!!!
While most of us roll our eyes when we see the seemingly daily forecasts on imminent AVXL price and volume from George, it is not unusual for him to actually post some useful information or reference worthwhile stories in the media. I am responding to his Saturday post of an article from The Guardian (US) which gives a European view of the monoclonal antibody treatments for Alzheimer's. The researchers cited are suggesting that the benefits cited are proving harder to quantify than the potential harms. You have heard much of it before, but the article is a good read since we know that blarcamesine (A2-73) has gotten over the first hurdle at the EMA and is on its way to an MAA filing.
While Dr. Sebastian Welch, a dementia researcher with the University of Cambridge is not terribly troubled over the ARIA side effect risks for the vast majority of patients (at least for those not on blood-thinning type medications), he is skeptical of selectivity of the trials where 80% percent of the patients were screened out as ineligible. To my way of thinking, he delivers the real "money shot," saying if, when prescribed in the real world, "the drug eligibility is restricted to match the trial eligibility, then very few people will be eligible. If legibility is broader, then the already small effects are likely to be even smaller and the side-effects more pronounced." That no doubt has been pointed out to the EMA (and will be to the FDA, if it has not been already) by the Anavex team in touting the superiority of blarcamesine.
Curious, is it not, abe, that it was only a 12 week study?
I guess you are not talking about their Parkinson's trial...
tschussmann, depending if and how you use leverage in that brokerage account, you should be able to restrict your broker from lending those AVXL shares out. Back in the day, my institutional clients loved to do that with heavily shorted stocks, making it known to their fellow institutional shareholders when they were doing that. The resulting squeeze could not only cause some short term levitation in the price but create outright panic when positive news hit the tape.
"13. Defendant Christopher U.Missling is and was at all material times Board Chair, CEO, President and Secretary of Anavex."
It would suggest better due diligence from the shysters at Levi & Korsinsky if they weren't wrong about Missling being the Board Chair currently and at all material times.
I would imagine, sage, that there was some dialogue with the FDA in the second half of 2023 when he could have brought up that idea you alluded to, AA with the OLE serving as a confirmatory trial. Again if I were guessing, he got some push back on that, so we have the more recent statement from him (in a conference call Q&A?) that the OLE would be part of the NDA package.
By "claimed," frrol, I meant that Missling said those things. As I suggested, I have no idea if they were statistically significant.
So, what can be said about the FDA's move to call in an advisory committee to review Lilly's drug application for Donanemab? First of all, a similar move was made during the Biogen/Eisai application for Lecanemab (LEQEMBI). However, at this late stage it was totally unanticipated by Lilly and the stock market. Predictably, LLY is down sharply today (shedding over $15 billion in market cap) on a day when Big Pharma stocks are up (despite Biden railing against prescription prices in the US last night) and BIIB is outperforming the group. The BIIB move is logical on the theory that it will have quite a few more months to establish LEQEMBI in the market before Donanemab is approved, assuming it actually is.
Beyond that, however, the publicity around this review (as well as the one currently being conducted on LEQEMBI by a Scientific Advisory Group for the EMA) is not helping the cause of monoclonal antibody treatment in the eyes of physicians and caregivers. LEQEMBI is already underperforming the initial targets set by Biogen/Eisai in the marketplace, and in recent special edition I noticed a poll taken by publisher "BioSpace" in which response to the question "Do you believe the current data show a benefit worthy of LEQEMBI's $26,500 price tag?" was 32% Yes, and 68% No.
In answer to sage4's question as to whether this is good timing (for Anavex) I would say it surely is. Both agencies, EMA and FDA, clearly have factions that are skeptical of the benefit to cost ratio - cost including safety, convenience of administration, and expense. Whether they approve LEQEMBI or Donanemab, respectively, or whether they don't, it seems that the outcomes will have been contentious. The physicians who prescribe for Alzheimer's patients by now fully recognize that there are significant limitations to what mAb therapy has offered up so far. The appearance of a drug application for Blarcamesine with a different solution (in a pill) that matches or exceeds the efficacy of mAb's in a shorter period of time, eliminates the risk of serious side effect, and slows brain shrinkage instead of accelerating it, will be taken very seriously at both agencies. (I didn't even mentioned the claimed benefits of better sleep, reduced blood pressure, improved tau levels and reduced inflammation, where we haven't seen the data yet.) So, yes, I think the timing of these calls for advisory groups, which is sparking renewed controversy over the mAb's in the press, coupled with apparently lackluster LEQEMBI sales, is very beneficial for Anavex's cause.
If you hadn't called the presentation a non event, I wouldn't be disagreeing with you, Investor. Whether there is any material information that is new to you or me is irrelevant. What is important is that this, to my knowledge, is the first presentation of the summary information from the Phase 2b/3 trial to an audience in Europe. It is not targeted to institutional investors, as was the TD Cowen presentation on Monday. It is targeted to opinion leaders - researchers and health care providers in the field of degenerative neurological diseases. It is being delivered not by a CEO but by a scientist, Timo Grimmer, well known in his field internationally and particularly in Europe. It is part of the first salvo by Anavex to get approval for Blarcamesine on the continent, and it comes at a time when there is little enthusiasm for LEQEMBI, whether or not that drug gets approved there over the next month or so. In my view it is a real event, not one that should be measured by whether it moves the stock at all on Monday.
Yes, plexrec, you can register for the online version of the conference. If you are not a nurse, student, or citizen of a third world country, you will pay 450 Euros for the privilege (last I checked), or E30 for every minute that Grimmer speaks. If you are good with that, you have to stay up very late tomorrow or get up very early early on Saturday to hear it. Go for it!
He doesn't have to read through the Safe Harbor.
Enquiring minds want to know!
Joseph, as to your question regarding submission announcements by the company and/or the EMA, I can recall on at least one occasion Missling saying that the company would announce the filing of a formal drug application. (I don't know if he meant after acceptance or prior or both.) As to the EMA, my correspondence earlier in the year with a Greek woman in the Regulatory Affairs department yielded the following response: "There is usually an announcement at the start of the marketing authorization assessment when the dossiers are received which you will find out by following the announcements that EMA is doing periodically." Vague enough for bureaucratic purposes?
Excellent succinct summary, boi, of what I too believed were the newer and most salient elements of emphasis in yesterday's presentation.
In recent weeks I have read a couple of reviews of Donanemab and/or Lecanemab (LEQEMBI) in which the commentator expresses his/her concern over the accelerated brain shrinkage caused by treatment with these monoclonal antibodies. The fact that Blarcamesine actually slows the shrinkage vs. placebo is a stunning contrast.
Indeed, Slide 21 (at about 14:30 of the presentation) was the juicy new bone that Missling threw out from the data pile. Larger and faster improvement in the plasma AB 42/40 ratio vs. placebo for the blarcamesine patients than those treated with LEQEMBI was impressive and unexpected. Nice to see this biomarker show an mAb beaten at its own game, even if it isn't the one blarcamesine professes to play. I suspect the EMA will enjoy that slide.
You are also spot on with your observation that Anavex looks set to push the restorative effects found in its genomic study, and I also fully agree that this was a superior presentation from what Missling has often delivered in the past.
Was she not the TD Cowen analyst/moderator?
Why didn't the small group of 5%-15% make the cut? Well, if LEQEMBI fails at the EMA in the next couple of months after a review by an SAG called in to render an opinion, we can say that one of the applicants (or about 1% of total, as I recall) did not pass in terms of the efficacy/safety ratio and/or an efficacy/cost ratio.
Yes, plexrec, the timing is actually quite good with impending donanemab approval turning some attention back to Alzheimer's. Furthermore the forum is excellent, Missling not having presented at TD Cowen recently (if ever?), and offering a solid institutional audience, the majority of whom have never heard the story before. The time slot in the afternoon of first day is a good one as well. The presentation by Grimmer at the end of the week, albeit to the wholly different audience of his colleagues, is no less important and no less timely in my view.
Thanks for recommending me for a slot in the marketing department. I was in media before the investment business, and once upon a time worked in the building which was the previous HQ for Anavex. Rockefeller Center would be fine. I could walk to work and eat the delicious "Bison au Poivre" at Le Rock downstairs. I will give it some thought...
Yes, Besao, I saw part of Cramer's pitch on Lilly, and he attributed part of the recent strong movement in LLY to the anticipation of FDA approval for its new Alzheimer's drug, donanedab. I believe the company suggested that approved was expected in the next week or two. Like the Biogen/Eisai drug, lecanemab (LEQEMBI), as well as its now defunct predecessor, aducanemab (ADUHELM), donanemab is a monoclonal antibody (mAb) treatment that reduces the quantity of amyloid plaque in the brain and therefore hopefully retards the development of Alzheimer's. After decades of work in pursuit of that theory, the results from the mAb's have been disappointing to put it mildly. Donanemab might be somewhat better than LEQEMBI, but it certainly seems a huge stretch to call it a game changer. Like the others it requires infusions at a medical facility. The side effects can be quite serious, particularly cerebral edema potentially leading to life threatening brain bleeds. The latter possibility requires patients to receive regular brain scans. In addition, like its mAb predecessors, it accelerates brain shrinkage. Also a significant number of patients in the trials apparently dropped out because of nausea.
If you indeed read this board regularly, you know that blarcamesine, Anavex' current entry in the Alzheimer's field, does not have the serious safety issues common to the mAb's. There is no cerebral edema and therefore no need for ongoing brain scans. As I recall, there was no issue with nausea, as seemed to plague the donanemab trials. Some patients reported mild to moderate dizziness, and the company now recommending an evening dosing protocol. As you mentioned, it is a small molecule oral drug, in contrast to the mAb infusions (which may evolve into injections). As to efficacy, I would refer you to page 19 of the new (2024) Anavex Corporate Presentation on the company website. No longer does Anavex need to compare itself to ADUHELM, so now we see a chart of ADAS-COG showing that blarcamesine slows the cognitive decline vs. placebo by 28% over 48 weeks. That is a faster and stronger response than donanemab, which slows the cognitive decline vs. placebo by 19% over 76 weeks, as noted in the sidebar. I am sure that Missling won't fail to highlight this at the TD Cowen presentation on Monday.
So, of the two which is more likely to be the game changer? The stock price of AVXL should take care of itself after an MAA is filed and accepted at the EMA and and/or after the peer reviewed article is published.
Pretty spiffy, that VKTX. An incremental $5 billion in market cap today on a Phase 2 in an increasingly crowded field. Total market cap = $9 billion; total revenue = 0. Bodes well for other pre-revenue companies that might succeed in gaining drug approval for a large market indication.
I agree with you on that, plexrec, particularly if that one presentation is all that someone is registering for. Since it is only 15 minutes in total (with little if any time for questions, I imagine) and since you have access to most of the likely content in the company's latest presentation piece, it is not really a question of new information for you and me. I think the significance of this is that it appears to be the first presentation on the data and biometrics from the 2b/3 trial to a European audience, and that it is being done by Timo Grimmer. It comes at a time when an SAG for the EMA is being called to give its opinion on Lecanemab to the Agency, which appears to be deadlocked on the issue (or at least looking for cover). It is also being delivered by an extremely respected Alzheimer's expert on the continent, who seems to me to be taking a more aggressive stance on the advisability of near term approval for Blarcamesine than might have appeared to us a year ago in the company conference call or the MayoMobile interview. Aside from being naturally cautious at the outset, I might speculate that he was quite impressed by the biometrics available since then, in particular the slowing of brain shrinkage. The key here will be the reception he gets with his colleagues in Europe. I think it will be quite positive.
Plexrec, I looked at the PD/AD site a week or two ago, and as I recall, you could sign up as an offsite participant and have access to any presentation that you wished, either live or previously recorded, up until the end of the conference (March 9th) for a fee of 300 Euros. A somewhat higher ("Gold Track"?) payment allowed for access after the conclusion of the conference. The time difference between Portugal and EST here is five hours, I believe, so you would have to get up early (or if on PST, go to bed late the night before) to hear it live.
Gute Frage, Missing. Rereading the FQ4 conference call transcript gives a strong hint about your speculation.
In regard to waiting to following up with the FDA, I would reverse it a bit. I think Missling was waiting for the EMA application process to be set in motion and also to (diplomatically) confront the FDA with the results/projections for Leqembi, the most recent mAb to come out of Biogen (following Aduhelm), be approved by the FDA, and come a cropper in the market.