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You need to understand what an “intermediate endpoint” means. It is ANY clinical endpoint — that is “reasonably likely to predict final/established clinical endpoint” as per FDA.
Is OR “reasonably likely to predict improvement in delta-Cog or delta-ADL”?
I’d say yes, if n is high. Of course. Thus. FDA may easily consider OR as an intermediate-endpoint. But approval may depend upon n and other factors (dose arms, etc) — which imo makes it unlikely.
No. I’m saying that these effects (that you meant) are transient/minimal — they don’t suppress a $50 stock to $10 (with 1B market cap) for months.
No, AA has two pathways. Surrogate biomarker OR intermediate endpoint. Look it up.
https://www.fda.gov/patients/fast-track-breakthrough-therapy-accelerated-approval-priority-review/accelerated-approval
On initial thought, ORs as an intermediate end-point for AA is plausible. But here are the issues with that:
1. AA would have to be broad label, since the trail was. It’s very difficult for me to imagine that FDA would restrict the label to responders — almost impossible, for various reasons.
2. Given #1, for FDA to give AA based on ORs, the n would really have to be significant (at least 30%, I’d say).
3. Also, Given #1, the confirmatory trial would have to be broad label too — with delta-Cog and/or delta-ADL as the final endpoints.
So, AA based on ORs as intermediate end-point is plausible but unlikely.
Doesn’t answer my Q or satiate my curiosity. You guys are only trying to make me believe too (it doesn’t matter whether it’s true or false — doesn’t answer my Q).
These believers believe that AVXL should be 50-100 (even with unsatisfactory results) but is $10 for months due to some conspiracy!
Yes, stock manipulation happens. Yes, insider trading happens. But that doesn’t mean a stock will be at $10 for months instead of multiples. Or a stellar result has muted reaction for months.
The same guys also think that if I have owned the stock since 2015, I should have been on this board discussing silly since then! And, what is the relevance of this anyway? That it means I’m short and I’m here to influence others to short?! Really?! We/You have zero ability to move the market. Eg, abc4… bought 30k shares a few days ago (that’s a lot of shares for anyone here) — did it move the stock at all?! Zero. Stock only went from $10.4 to $9.4 after that.
I’m here for knowledge—and yes, there are a few posts and posters, who provide that sometimes. Exceedingly little though.
Anyway, I was genuinely curious as to what drives people to believe in such conspiracy theories. Unbelievable, to me. My guess is limited experience and knowledge about stock market. Stock market is not perfect — stocks don’t reflect the true price always (esp, low caps) — not because of some conspiracy but because of uncertainty or lack of conviction from the market. AVXL has many other problems — perhaps temporary and surmountable (that’s why I’m still long).
The only semi-confirmed/believable direct communication with FDA has been with regards to the endpoints of EXCELLENCE— as noted in the last PR (ER).
AF has been right all along.
Immediately after each of the trials -- AVATAR and P2/P3 --- he pointed out the glaring flaws. I looked past them, and thought he was being overly critical. Well, it's obvious now that he was right -- RSBQ-AUC and ORs are both made-up endpoints (data engineering, as he calls it). CM has admitted to RSBQ-AUC being made up. For ORs, we'll know the truth, when he admits a need for P3 himself.
My bar for EXCELLENCE success is --- AF must be impressed by the results.
I made the post on Wednesday when the stock was at $9.7. Technically, I had a feeling that it was on the rebound. Time will tell ..
Buy it all … it’s $9.7 now.
Indisputable fact.
AVXL never disclosed the endpoint measures (i.e., odds-ratios) and the thresholds to be used for the P2b/P3 before TLR on 12/1/22.
Same thing happened with AVATAR -- they never said they'll use RSBQ-AUC, until after they had the data.
Which other company has ever done that?
It won’t be (less than $20).
IMO, market is smart. They know that P2b/P3 has no chance of supporting approval. The stock is still around $10. I think thats a fair price or even lower-than-fair price, even with a P2b/P3 semi-failure.
BTW, I should correct myself --- I don't think P2b/P3 has failed altogether.... I'd say it just has no chance to be pivotal (Meeting delta-Cog and CDR endpoints is very commendable, and perhaps, the reason that the stock is still worth buying).
That's you, not me.
I have accepted that P2b/P3 was a P2. With that acceptance, is AVXL a bad buy right now? I think it's a "reasonable" buy, at this point --- especially based on the trading activity since it bottomed $7.5.
Time will tell.
No, I didn’t say AVXL is going down. I believe it’s going up — just not to $100 (as I dreamed of, before 12/1/22 debacle). Am very happy with $15-20 in short term now.
No one (including insurers) is mandated to pay/cover an FDA-approved drug, as per my understanding. Certainly, not the ones that are AA-Ed (many precedences for AA ones not covered by insurances).
FDA doesn’t take cost into consideration at all. And, rightly so.
CEO may or may not have picked the endpoint measures post-data, but that’s the impression he has given to the world (anyone sensible). (FACT: CEO never before 12/1/22 disclosed the endpoint measures and the thresholds used).
But, IRRESPECTIVE of the above, the endpoints chosen (odds-ratios) are never-used-before and meaningless (esp without n, and without dosage-wise) from an approval point of view.
There are a myriad of other problems. (1) Numerous inaccuracies/mistakes in data analysis, (2) Likely incorrect (one-tailed, Ie 1/2 of actual) p-values published, (3) No analysis per dosage arm, and finally and most importantly (4) ZERO clarification to these issues even after 9 months post-completion of trial.
Make your own judgements. Above are almost-facts, perhaps some of them are tainted by my assessments.
My summary assessment of P2b/3 is:
The trial failed.
CEO decided to hide it.
CEO has accepted it to be a P2, thus zero urgency for any updates/FDA-meetings/filings.
Once we accept the above, everything else will make sense (including, pps).
It's a BFD, in the AVXL world.
Too much to write .. but the short story is: AVXL's CEO picked the endpoint measures that suited him/trial, and reported success based on that. That kills any notion of trial success. Moreover, the endpoint measures he picked (odd-ratios) have perhaps/likely minimal relevance to "meaningful clinical benefit".
haha. Foremost, because AVXL hasn't even filed an NDA. :)
Not diversified at all. At one point, I was 97% SRPT. :)
Yes, Etep shouldn’t have been approved going purely by data. But JW went with her intuition (rightly so, imo). So — lucky, I’d say. But after that — it has been great execution. I do love SRPT’s CEO. Going forward, the potential is huge (as is true with any biotech — but with SRPT I have belief). I bought 1/2 at $7, and 1/2 in 30s. Still holding for a much bigger payout ..:)
My portfolio is 85% SRPT, 10% AVXL, and 5% a couple of other stocks.
How is Rett a slam dunk?
Do we have a P2 that shows statistically significant improvement in delta-RSBQ (the endpoint of P3, as of now)? As I understand AVARAR didn’t show any ss delta-RSBQ improvement— only RSBQ-AUC.
Buy it all … it’s $9.7 now.
AVXL showing some sign of life ….. $11 soon.
For a serious company like SRPT:
Data in early May
FDA feedback in July
NDA Filing (if amenable) in September
Approval by 6/24.
For AVXL:
Data in September
Assuming positive data, FDA feedback in February.
Filing in May, 2024.
Approval on early 2025.
Good news — if the data is certainly positive, then CM’s ineptness causes only 6-month delay (in my eyes).
Avxl could easily fooled the Aussies into believing (just like the pumpers here) that the P3 trial will start ‘soon”. I’m sure they don’t know what that means in AVXL language — 2-3 years?!
Certainly possible
Wow. You have high expectations.
Why do you want to deprive people of well-deserved fantasies?
Me too. I sold 15% of my holdings at 11.9 (lucky!), and bought it back to 10.08.
I don't think this will break 9.5.
Well, FDA judged it to be “tolerable” — Ie, the risk/benefit to be favorable. I personally don’t disagree (since patients have a choice).
Unfortunately, that’s not how FDA decides on approval. It follows the law on what is required for approval — even if it sometimes misjudges the evidence.
For approval, you need “substantial evidence” of efficacy — which is defined as “two well-controlled and one very compelling clinical trial” demonstrating statistically significant efficacy of clinical endpoint. Of course, the safety should be “tolerable”.
For AA, same as above — except replace the last phrase “clinical endpoint” with “surrogate market or intermediate endpoint which reasonably likely predicts the clinical endpoint”.
Does P2/3 satisfy the above? I certainly don’t see any surrogate marker or intermediate endpoint, yet. So, AA is out.
Regarding full approval — the OR endpoints aren’t going to cut it IMO. The delta-endpoints may — but AVXL is hiding many aspects of them, so they are likely insufficient.
Why would serious investors sell at $10.35 when they could've sold at $11.50 or $11.90?
And why would they be selling when XBI is rising?
Seems "someone" is trying to hold the price down.
You got my attention.
What’s your thesis (or basis) in short?
I have a comparable amount, but planning to slowly unload. My main thesis is that AVXL is a very attractive acquisition target ($20-30 now), but of course not banking on it — but that provides a basis for stock appreciation. Nevertheless, hate the CEO.
Do you know if Avatar met the delta-RSBQ measure?
You think FDA will be happy with Avatar not meeting the delta-RSBQ endpoint? Certainly not.
Incorrect. A failed AVATAR (eg non-met RSBQ) and earlier studies will certainly have a bearing.
FDA will look at all trials. Yes, Excellence being the largest and final with have a much more significant impact, but if RSBQ wasn’t met in AVATAR then that is certainly a negative point.
It is the outcome of the Excellence trail that will determine if 2-73 is approved for Rett or not.
Maybe the committee members are crooks or incompetent!
Stocks always needs an EXCUSE to pull back. I have a strong belief that AVXL will cross $12 this month.
Haha. Such cluelessness.
Immediately afterwards we had a bull trap rise followed by a takedown so that the big players could make money both ways.