Replies to post #447660 on Anavex Life Sciences Corp (AVXL)

[boi568]

"Group statistics have little predictive power for a single member of the group."

That isn't true. It isn't even true for your coin flip example. The comparison is properly made between membership in groups with different expectations. Anavex is far better off in an 85 percent expectation group than a 15 percent expectation group. You are better off in a 50 percent "coin flip" group than a one percent group.

The reason why the EMA news is a big deal is because blarcamesine is now known to have moved into a very favored group, even with all known drawbacks of the 2b/3 trial. Relitigating familiar 2b/3 issues at this point is therefore akin to double counting.

Further, within a group with a high expectation of success, like 95.7 percent (the EMA approval rate without considering withdrawals) for example, there is much less opportunity for meaningful expectation differences among subgroups. Say there are ten equally sized subgroups of nine among ninety fully processed submissions per year (approximating EMA annual opinion totals). Once one subgroup of nine experiences just four failures, the other subgroup expectations all move to 100 percent; 4 of 9 failures, 55 percent, is a hard subgroup expectation floor, just by arithmetic. (And if that were the case, you would see those qualitatively distinct numbers separately described.)

I realize there is resistance here to this good news for a variety of reasons that I can identify, such as bad faith, ego, and other psychological factors, but these are not actually refutations of the EMA basic math. You are giving that a try, but there are serious arithmetic limits to your counter argument, and even then you are making assumptions about blarcamesine's differences within its group for purposes of argument that have not been identified in practice.

Frankly, I do not believe there is anyone present here qualified to make this type of differentiation. It would require broad knowledge of EMA internal decision making. That cuts down the necessary expertise to involved EMA staff, or perhaps a professional consultant assisting in multiple submissions (if such people exist, which is doubtful.) Without the access to context, there is no opportunity to make a comparison between Anavex's chances and the chances of others in its current EMA group, leaving us, again, at 85 percent.

I make the necessary concession that we are not quite at the MAA submitted stage; I also have been unable to identify any obstacles to reaching that point, or seen any such obstacles identified here by anyone else. Missling, of course, has stated his intent to now apply. So my concession is not much of a concession as far as I am concerned.

[Joseph_K]

I'd put the problem with the 85% chance of approval for the MAA a bit differently. Mathematically, there would be an 85% chance of approval if the application process was like a series of coin tosses. You don't know how the next coin toss will come out, but there's always a 50% chance that it will be heads up; or if you're throwing a standard 6-sided game die, your chance of it coming up as, say, a 3 is 1/6 or 16.666%. (Your chance of it coming up with any one of the other five numbers also is 1/6.)

But the EMA's approval process is not like a series of coin tosses. It's more like* an individual NFL team's chance of getting into the playoffs.** If the NFL process for awarding playoff spots was like a series of coin tosses, then at the beginning of the 2023 football season last September, the Chiefs had a 43.75% chance (14/32) of making the playoffs, as 14 of the 32 teams will get into the playoffs; likewise, the Cardinals had a 43.75% chance. But anyone who follows the NFL knows it would have been stupid to assign the same likelihood of success to the Chiefs and the Cardinals, because getting into the playoffs is not random like the toss of a die.

Just like you need to weigh each team's chance individually based on what you know about it, you need to weigh each drug application separately. The chance the Cardinals would have gotten into the playoffs was much less than 43.75%; it was, however, higher than it would have been if the NFL process gave playoff berths to only 4 of the 32 teams.

Doc, for example, sees blarcamesine for AD as analogous to the Cardinals -- not impossible it gets approval but much less than the random chance of 85% because of various factors including his conclusion that the ADCS-ADL co-primary endpoint wasn't met. Someone else might see blarcamesine's chances as 70%, or even 95%, because of various factors including its safety profile and ease of administration. Saying that Anavex has an 85% chance of approval is based on the mistaken premise that the process is random; it's not. Nonetheless, there's reason to consider the likelihood of blarcamesine's approval as higher than if the EMA had a history of approving, say, only 10% of applications. The EMA's historic rate of approvals is just another factor to put on the scale for determining the chances of approval -- it's not the percentage chance of approval in itself (just like the likelihood of the Cardinals getting a playoff spot was not 43.75%).


* It's "more like" rather than "just like" because the percentage of teams in the playoffs is fixed, whereas the percentage of MAAs that get approved is not.

** NFL "power rankings" before the 2023 season started, if you're interested:
https://www.nfl.com/news/nfl-power-rankings-preseason-2023-nfl-season

[frrol]

While we're on EMA chances, important for everyone to keep in mind that our drug administration and cost advantages will have little bearing on the CHMP assessment. It's the EC that will consider them, when giving their final authorization decision. The CHMP will be focused on the completeness of our MAA, and the trial design and safety/efficacy results it contains.

[bas2020]

You can't treat the 15% miss as purely by chance (i.e. coin flip). You must take qualitative factors into consideration.

My point is that based ONLY on the 85% success rate that doesn't tell you which of the applications will be in the 85% or the 15%.

For one, what were the AEs for the 15% that didn't get accepted?

Qualitatively, blarcamesine is looking rather good with both efficacy and safety profiles.
No worries here about approval this year.