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Not sure I see the concern unless the drug has shown some issues preclinical. I mean not being anle to have sex could be a drawback but 14 to 24 MMSE would seemingly be pretty old. Extra cautious I guess.
I did notice that Annovis MMSE range for the upcoming trial is 14-24. I also noticed this oddity. Never seen that before in one of these trials.
Sexual abstinence (sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatment. The reliability of sexual abstinence needs to be in relation to the duration of the study and the preferred and usual lifestyle of the participant) *Non-childbearing potential includes surgically sterilized or postmenopausal with no menstrual bleeding for at least one year prior to study start.
Male participants must be sterile or sexually inactive or agree not to father a child during the study and one month after the last dose of study medication and must agree to use a barrier method for contraception. Female partners of male subject must adopt a highly effective method of contraception with a failure rate of less than 1% per year when used consistently and correctly such as:
Oral, intravaginal, or transdermal combined (estrogen plus progestogen) hormonal contraception associated with inhibition of ovulation
Oral, injectable, or implantable progestogen-only hormonal contraception associated with inhibition of ovulation
Intrauterine device (IUD)
Intrauterine hormone-releasing system (IUS)
Bilateral tubal occlusion
Yes it could. FDA allowed for subgrouping in the SPA according to the FDA clinical trial website. If it feels that enough patients are getting treatment benefits in the 20-26 MMSE grouping, yes the drug could be approved for this group. Most companies are only running tests in that population anyway. I think most expect the company to understand the answer to this question and to adjust in their recruiting accordingly if need be.
Interesting study. Thanks
Sounds like you have this on the brain as much as I do lol. Praying one day one of these companies can make a difference. I do think Lecanemab is a step in the right direction. Hopefully one of the alternative MOAs will prove better and safer.
It's no problem to change protocol to add more patients for any variety of reasons. Might take patients. I'm sure the company is still going through the data they have at this point. Company is spending too much on this trial to take on added risk. They'll figure it out.
But top line isn't on the mild patients only. Its on all the patients. That's why you didn't see a top line p value this time. Up until this point results were stat sig but have progressively gotten worse.
Looking at those charts seems like the difference between mild and moderate in the placebo is roughly a point, but closer to 4 pts on treated groups. I don't think simple placebo randomization is going to take care of top line results. Company needs to amend protocol or add more mild patients at the end of the trial I believe. We didn't see p value for 12 months as we had at earlier time points so impossible to say.
Ha ha. Hang in there Mac.
It really has nothing to do with brilliant minds. It's up to what the FDA realistically expects. Placebo controls are more reliable than everyone in a trial knowing they are taking a drug (OLE), especially in a population that is so mild that roughly 20% are misdiagnosed. I know at least one BP that assumes that rate in one of their early AD trials. Those are just the realities and why it takes so long for approvals whether right or wrong. I promise you that there won't be a 47% "super responder" group in the current trial but lets hope for something as close as possible. It will be 2 years before we know however. I'm thankful SAVA hit the ground running and are running concurrent trials.
Looks like an analyst downgrade this morning as well. Remi needs to figure it out quickly. For the record, I haven't owned shares in quite some time.
If they don't, it seems likely they will fail top line results. Where it goes with the subgroup of mild patients is anyone's guess. They'll still have 500 or more in the mild groups to judge from but still will be viewed a failure by the usual suspects. I think Remi needs to make the market aware of the situation and any remedies the company may try to take involving recruitment at some point.
Yeah I always enjoy his posts.
I do wonder if the company is able to recruit more heavily towards the mild population this second half of the recruiting cycle. At the same time the SPA was approved with the 2 subgroups so it may not matter. It's just odd that the results have gotten less impressive over time. It seems it would be more equal as far as the severity of patients over the course of the study. Certainly makes it more of a gamble to me.
Not really anything to debate until competitors release full data. Until then folks can pretend as they wish. If there is a mistake in any of my arguments, I'm happy to admit it. The posts I made regarding this MMSE scoring issue were on this board to the poster I linked to which is the only reason I even addressed when someone passed this along after today's SAVA PR. No worries. Hope all is well with your health these days.
Someone sent me this because many folks are trying to make comparisons. It's why message boards are so dangerous but a great place to discuss IMO. Now I repeatedly pointed out last summer that Anavex provided NO benefit for patients scoring below 20 on MMSE in their early trials and this was why their recent trial included no such patients. I also repeatedly pointed out that SAVA included all the way down to MMSE of 16 in their OLE and now also in their FDA approved trials. SAVA reported results on that 200+ patient OLE today both with mean overall scores (patients worsened as a group) as well as the prespecified subgroups of 16-20 and 21-26 (this higher group of 133 patients improved greatly). Seems to me the most beneficial comparison would be an apples to apples comparison of similar grouping of >20 MMSE scores, keeping in mind Anavex includes up to 28 which is even more mild. What doesn't seem valid would be claiming the average Anavex patients did better than the best SAVA patient on average as was portrayed in the following post.
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=171024028
"On average, patients, who improved cognitively with ANAVEX®2-73 treatment, improved by ADAS-Cog cognition score of -4.03 points" Well of the small percentage of patients who apparently improved (of course a number still hidden) they improved by average of 4 points VS for SAVA
"In the mild sub-group, ADAS-Cog scores improved, from 15.0 (±6.3) to 12.6 (±7.8). That's EVERY patient in the same scoring parameters of the Anavex trial (MMSE>20) which improved an average 2.4 points. Now if 10-20% (best guess based on what we know at this point) of Anavex improved an average of 4 points then the other 80-90% of the patients apparently GOT WORSE on average since PR said of "those that improved). If 100% of SAVA patients improved by an average of 2.4 points how could one make the claim that the Anavex drug is better? Surely 10-20% of Sava patients improved by an average of at least 4 points while the average of the other 80-90% IMPROVED. Just my thoughts and 6 months after completion of Anavex trial investors are still waiting to see such "mean" scores for the entire group.
How the placebo impacts this is up for debate but board readers have heard for years that placebo doesn't matter in AD right?
Lot of truth in that. My recommendation has always been you need several hail Mary attemps because even 1 or 2 in every 7 or 8 can result in a pretty good overall outcome.
I think in early AD as many as 20% can be misdiagnosed so is an issue.
Now that I'm on my desktop I can see that 133 patients were in the MILD group which is better than if the numbers had been reversed of course.
The scores from the mild group are clearly better than some recent competitor drug trials from patients in that same MMSE 21-26 range. It's the lack of placebo control that bothers me but I understand some placebo controlled data could be released this year although the issue won't be put to bed until P3 data is released.
I double checked the clinical trials website as I was concerned this 16-20 and 21-26 subgrouping could be an issue with total number of patients in the current trials but looks to be part of the SPA agreement so if only half those patients in the two treated groups are of the mild subset, everything is still a go.
That's the number we need to see. I think the rest of the results can be thrown away at this point. Hopefully its over half the patients and probably is but the 23% or whatever it was that declined slower is likely cancelled out by the lack controls. The mild group scores seem to show so much of an improvement that it would likely overcome that drawback. Either way I'm a bit disappointed with the overall results but since we are on the backstretch of enrolling the P3 FDA approved trials, not much to do but be patient at this point.
Glad I could help. Unrealistic expectations here and is the case with all these spec plays. Sometimes we win. Sometimes we lose. SAVA clearly leads this space and their SPA is potentially huge. Today's results did nothing to increase the odds of the eventual trial readouts IMO. However if they are reproduced in that 20-26 MMSE score range, it would be a much better result than we have seen from anyone else. Once again, how much the original trial not being controlled factors in as a wild card that keeps this into a longer shot than if original results had been controlled IMO.
So you sold before the results? Lol
My apologies for asking. I'm busy at the moment but do we know how many patients were in the MILD subgroup? Those results seem better than I would have figured but I admit the overall results are worse than most might have thought. This is what I've been pointing out the last couple weeks to Tootall. Eliminating the lack of placebo issues (which is dangerous) you seemingly now have a better comparison to most competitive drugs as that MILD subgroup is now more similar. Allowing patients MMSE as low as 16 had previously limited any apples to apples comparisons IMO.
I'm not certain that's what you're about to learn but I hope its close enough
We've only tested it for 1 of the 3 planned indications. At this point we don't know. For the 3rd straight trial the drug has performed better than placebo, just not that much better. We still have OLE data and 40 week data as well as the complete data set from the recent trial to make a determination of where to go next with AD. It's too early to say at this point I believe.
Thanks for the props but I've never been a Silverman apologist other than to say he would never be voted out. I've been around long enough to know things that were done to save this company years ago that gave bryostatin a fighting chance. I'm not going to say he saved the company by putting in a poison pill and turn around and say he's leading corporate raiders this time however. What I do know is shares have a cost basis. If someone can tell me how Haywood who bought in before the reverse split at split adjusted $30+ dollars (and many lenders well higher than that) and apparently has sold out this year (especially if he held to Dec 20 so he could vote to approve shareholder dilution at prices approaching a dollar so he could reload). How could he have done anything but lose his ass off and I'm just using him as an example.
I wouldn't buy a new share here until a plan is in place under any circumstances. The convertible deal WILL cause dilution and keep the share price muffled at best. I don't need to pretend that folks who sold high dollar shares (split adjusted) for a buck (and the volume sure shows the lenders still had the shares through these results) are making bank off the company by receiving cheap shares for their loan at the same price they just sold . That's all I'm saying. I have no reason to believe the lenders have made big money. If they held through results they got screwed big time.
Selling shares you paid many fold higher than, to get lower priced shares in a hope you could sell those higher maybe never could lose folks a lot of money
No idea but he was one of our biggest holders, had his shares reverse split, and has lost his tail on this one. You can't expect people to pay the equivalent of $40 per share factoring in the split, sell at 1.20 or lower (if you believe he's part of the convertible and held through December 20 just so he could vote) and then maintain the PE folks are ringing the cash register here. The original PE folks have been split twice if you can imagine what those shares cost and then for some reason we think think they could never sell the shares but warrants now in hundreds of dollars and never exercised were "unfair" sweeteners. No doubt these guys influenced share price to get as many shares as they could for their investment and will do so again. That's why this is an unsound investment until they can prove out bryostatin for an indication. Just bizarre to me to think somehow they are making fortune off this one but that's JMHO. I voted NO because I haven't heard a clear path forward and last time they screwed the pooch with extra money.
Looks like George Haywood has sold out. Now that dude lost his tail off.
Well anything they've sold are at huge losses. If that doesn't show how risky it was, I'm not sure what would. This time next year folks will be happy to have that extra 15 million is my guess, unless they waste it away like they did a few years back.
I think once they lost big on their original 20+ million in 2016, they have done anything they could to minimize the loss while extending the upside hopes with warrants. At this stage of the game, looks like they took a bad gamble. Its hard to make millions back in an illiquid stock. The only real hope they've had is to find success in a trial and so far that's been illusive
They always had warrant upside but have likely lost millions here funding the company on a gamble and having to scramble to keep it solvent while minimizing obvious losses. They announced shareholder record date a couple days after Christmas I think and yes likely insures shareholder approval unfortunately
Those PE folks took a bloodbath on a lot of shares if they did sell. Only way to minimize the convertible dilution moving forward is to vote NO. I have as well.
Not that many short going into results. Been more adding afterwards based on the reports. Looks like very few came out to the good.
Unfortunately not as successful as some others.
Not sure at this point. Will be at least a month before we see OLE data I would think
I certainly don't think the 12 month falls off a cliff. The shorts have pointed out that the first 50 patients performed much better than the second 50 patients. Then we started hearing Springer say that maybe some other types of dementia maybe filtered in to the second 50. Doesn't really matter to me. I just don't think the full 12 month data will be as good as that original 6 month data but will still be much better than anything we have seen. For some that alone will be exciting. For some that have followed for years, it might be a little underwhelming.
The most important thing to me is the FDA wouldn't have granted the SPA if the early trial data had not been potentially impressive. Company has executed extremely well. It's just quite some time before we know.
The 12 month will be helpful for sure. The 9th month was good but started to show some issues which IMO will make the 12 months "less good" than the 6 month but still will be VERY good compared to the rest of the sector. My point is that comparing this data to any historical data or something Biogen just ran isn't even close to a realistic comparison and I certainly don't expect to wake up to a triple digit share price on 12 month data. I wish and hope it would but I don't see that happening. JMHO
I'm speaking about the original trial, not anything currently being run. It's not an apples to apples comparison. Now my link to current SOC clearly shows a significant percentage of patients will be stable or even improve over a year in controlled (randomized is controlled) trials.
You're missing my point. That data is on CONTROLLED trials and states it in the slide. There isn't 20,000 patient studies on open label trials for mild AD so that slide is a waste for Open label comparison but gives a good idea what investors can compare to in 2+ years. I gave you a link to actual trials that show folks already on AD drugs for mild AD that show 23% are expected to improve over a year. This drug isn't being compared to NO treatment. It's compared to current SOC which is what my link showed. Everything up until this point has been open label and is impressive to me but not what some try to portray it as. If I KNOW i'm getting the drug and folks are pumping youtube videos of anecdotal reports, then me and my whole family are much more likely to claim a better response.
None of this has anything to do with the current share price. I'm just talking about the science.
The question is, are patients on other AD drugs when in this trial. The answer is YES. How many patients actually improve over a year on these other drugs (donezepil in particular)?
https://alzres.biomedcentral.com/articles/10.1186/alzrt210#Tab2
All these trials have placebo responders. The point is, if you KNOW you're getting the drug then the response is greater. If you're in a controlled trial and don't know whether you're getting a sugar pill or the drug, well then the response isn't as big. Many seem to miss th is point. Once again, CEO stated in an interview after the 6 month results that no one really knows what a placebo response would be at a year because they don't know. In a couple years we will know.