Tag Archives: Limb girdle muscular dystrophy

The fact that not everyone responds to Simufilam is irrelevant to its eventual FDA approval

A very intelligent friend does not share my optimism about Simufilam.

“Is the data really that positive? ADAS-Cog mean scores changed minimally over 1 year in patients with mild-to-moderate Alzheimer’s disease.  47% of patients improved ADAS-Cog over 1 year by 4.7 points. But 23% of patients declined by <5 points. Mild patients responded better than patients with moderate Alzheimer’s.”

Why are these thoughts irrelevant to the eventual approval of Simufilam by the FDA?

First: no drug for anything works for everyone with the condition

Second: The assumption that Alzheimer dementia is a single disease is based on just that: an assumption.

An example: When I was running a muscular dystrophy clinic in MonrN (’71 – ’87), we saw something called limb girdle muscular dystrophy , in which the patients were weak primarily in muscles about the shoulders and hips. Now we know that there are at least 13 different genetic causes of the disorder.

If the clinical picture of Alzheimer’s disease is due to multiple causes, it is unsurprising that Simufilam doesn’t help all of them.

Also it is time for some humility about our knowledge about Alzheimer’s disease.  We have misunderstood what the senile plaque of Alzheimer’s disease really is for 111 years — see the following post written 12/22 — https://luysii.wordpress.com/2022/12/13/111-years-of-study-of-the-alzheimer-plaque-still-got-it-wrong-until-now/

Third (and probably the most relevant for FDA approval):  Less that perfect drugs will be approved if every other treatment is worse.

The example of immune checkpoint blockade therapy for cancer is particularly relevant.

Some absolutely spectacular results for the therapy has led to the approval of 6 different drugs in this class (all of them monoclonal antibodies against proteins involving the immune system).

One example [ Cell vol. 162 pp. 1186 – 1190 ’15 ]:  “20% of metastatic melanoma patients are cured with Ipilimumab, a fully humanized anti-CTLA4 monoclonal antibody.”

Would that results like this were the rule not the exception. Unfortunately — [ Nature vol. 565 pp. 43 – 48 ’19 ] “Most patients with cancer either do not respond to immune checkpoint blockade or develop resistance to it.”

So what.

Immune checkpoint blockade, despite being less than perfect,  is  still being offered to cancer patients, just the way Simufilam with its nearly 50% chance of improvement at 1 year should be offered to Alzheimer patients.  

I’ve hit the big time at last

I find this hard to believe, but the interview I did with Joe Springer on Friday 4 February  now has its own cliff notes —  It was a lot of fun while I was doing it, but the stress came before and afterwards.  People did seem to like it, judging by the comments they made while I was talking.