AMX0035 survival data

[Nikki J]

https://onlinelibrary.wiley.com/doi/10.1002/mus.27569?utm_source=ActiveCampaign&utm_medium=email&utm_content=Amylyx+Announces+Muscle+%26+Nerve+Publication+of+Survival+Analyses+from+the+CENTAUR+Trial&utm_campaign=Key+Study+Events%3A+M+N+Publication

this was published this week. As they note there is going to be some bias as it is likely those who were doing poorly might have opted out of OLE.

 

[EricInLA]

Thanks for posting this. It's difficult for a lay person to understand what they are saying, but do I read this correctly that these results seem better than the initial batch of results which people thought were disappointing? Is TURSO the same thing as TUDCA? I'm trying to decide whether its worth it for a slow progressing pALS like me to push to get access to this drug.

 

[Nikki J]

Yes Turso (taurursodiol) is TUDCA.
I think the issue with results was more the interpretation of results and the vote of the advisory committee. since that vote I have heard several times that the committee misunderstood some things / that criticisms made were not completely valid in the opinion of ALS specialists. I don’t remember the details but the interpretation of statistics was inaccurate supposedly ( of note the lone statistician on the board voted to approve). Just this morning Dr Cudkowicz mentioned that the unblinding due to taste criticism didn’t happen as they polled the participants and they were right/ wrong about whether they had placebo in a random pattern.

what should you do? Up to you. But consider. Slowing progression by 30 percent in someone with slow progression is a bigger deal than someone with fast. The TUDCA component is otc. You could see if you can tolerate it before fighting. The fda decision is due in a few weeks. I doubt it will be approved but you never know. Compounded amx0035 is a possibility. It is about 500 a month at one of the compounding pharmacies in the East

 

[EricInLA]

Thanks Nikki, helpful. You are correct from a math perspective that 30 percent is more significant if one is a slow progressor, but I wonder if the 30 percent figure will be accurate with respect to that subset. Intuitively it seems that it's easier to produce an effect on a fast progressing group (which I think was one of the critiques of the original Radicava trial in Japan).

In any event I've had the tub of TUDCA is my pantry for months now, but haven't yet cracked it open due to fears of what it will do to my stomach. I think I'll give it a try. I've heard about the compounding option too.

 

[Nikki J]

It is easier to see an effect in fast progression which is most of the reason trials are the way they are. I would argue that it is more than likely that those with slow progression ) are more likely to benefit from treatments because their disease is less aggressive. early disease is also going to be more amenable to treatment.

 

[steve613]

I read both the original and the newly published re-analysis of the CENTAUR trial. The original report published in the New England Journal of Medicine showed a prolonged survival of about 6 months with TUDCA/sodium phenylbutyrate. This new paper uses a different statistical analytic method to account for expanded access and shows that the "real world" survival advantage is about 8 months. It's a bit of hocus pocus, but the conclusion is intuitive, as many drugs have increased effect with prolonged duration.

I'm the husband of an ALS patient. We had to stop TUDCA/SPB (which we purchased at a compounding pharmacy for $500 a month) to enroll in a clinical trial. After looking at these two papers, I think when the trial is done we will go back on the TUDCA/SPB because it has a track record. If or hopefully when the FDA approves the combination, then it will be allowed in trials and not have to be stopped.

 

[Nikki J]

Here is an editorial by Drs Cudkowicz and Shefner ( both well known in the ALS world) giving their opinionson the FDA advisory committee criticisms and offering rebuttals https://onlinelibrary.wiley.com/doi...Ho7vCd7onNy-z3v5Q9O8U732Mijl68n3hbwfe3JLcLn7U