March 30, 2022
I’m Dr. Diana Zuckerman, president of the National Center for Health Research. We scrutinize the safety and effectiveness of medical products, and we don’t accept funding from companies that make those products. My expertise is based on post-doc training in epidemiology and public health, and as former staff at HHS and faculty member and researcher at Yale and Harvard.
ALS is a devastating disease and all of us want better treatments to be available as soon as possible. But today’s question is different: “Do the data from these 2 studies support a conclusion that AMX0035 is an effective treatment of ALS?” Your vote will set a precedent for other FDA decisions, just as FDA’s approval of Aduhelm set a very unfortunate precedent where science was ignored, delaying the research evidence that patients need and deserve.
AMX0035 combines TURSO and PB: TURSO alone was very effective for ALS patient in a small pilot study — and a large study of that supplement will be completed this year. You can see it on clinicaltrials.gov. Meanwhile, any patient can buy TURSO for 47 cents a pill on Amazon. Why not wait till that study is done, since there is no clinical evidence supporting PB?
Now, let’s focus on the strengths and weaknesses of the sponsor’s 2 studies:
The biggest problem with the open label extension is that it had no control group and most patients dropped out after a year – only 2 patients completed treatment! That tells you that there is a serious problem with AMX0035. We agree with the FDA that the extension data don’t support approval.
The RCT had one terrible flaw: FDA advised the company to create a combination measure of function and survival but the company refused. And when looking at the survivors, many patients in the experimental group had stopped taking AMX0035, so they should not have been counted as AMX0035 survivors. In fact, there were 5 deaths among AMX0035 patients and 2 in placebo. Since the placebo group was half as big, that means approximately equal mortality in both groups.
Here are just a few of many other flaws:
- There was a small change in the primary endpoint ALS daily activities score but almost 1 in 5 patients did not complete that measure
- 95% of patients were White – compared to 75% with ALS in real life
- AMX0035 had a strong taste and often caused diarrhea, so the study wasn’t really blinded.
And we agree with FDA that “The secondary endpoint results are not compelling or supportive of the primary endpoint.”
In conclusion: TURSO looks promising for ALS and is already available on Amazon for 47 cents a pill. A large multi-center clinical trial of TURSO will be completed this year. Why not wait till that study is done, and also consider interim results of the sponsor’s larger study of AMX0035 when there are enough data to find out their drug really works?