Why Cassava’s 1 year results should allow compassionate use of Simufilam

Cassava reported results on 100 Alzheimer patients in an open label (e.g. no controls) trial of Simufilam for 1 year — https://finance.yahoo.com/news/cassava-sciences-reports-second-quarter-131500494.html.  The average results were unimpressive (to the uninitiated) with only a minimal average overall improvement of an ADAS-Cog11 score of 1.5 points.  This is probably why the stock (SAVA) dropped a point yesterday after the news.  Since everything turns on ADAS-Cog11 here is a link to a complete description — https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5929311/.  The test takes about 45 minutes placing it out of reach of a busy practicing clinical neurologist.

Why is even the 1.5 point improvement impressive to the initiated (me)?  Over 32 years in clinical neurology, I’d estimate that I saw at least 1 demented patient each week.  Now probably only 300 or so of the 1,664 were followed for a year.  Guess what?  None of them remained stable for a year, and all got worse.  Absolutely none of them  ever got better after a year.  So at least some stabilization of the disease is possible for a year.  The statistics say that Alzheimer patients lose 5 points a year on ADAS-Cog.

But that’s pretty small beer.  Who wants to keep a demented patient around but stable.  Here is the remarkable part of the Cassava results at a year.

63% of the 100 Patients Showed an Improvement in ADAS-Cog11 Scores, and This Group of Patients Improved an Average of 5.6 Points (S.D. ± 3.8). The statistics say that Alzheimer patients lose 5 points a year on ADAS-Cog.

This is unprecedented and is a strong argument for quick approval of Simufilam (or at least compassionate use).

The cynic will say that I’m just looking at the happy part of the Bell curve.  There must have been people who declined to average the improvement in the 63% down to a measly 1.5 points on the ADAS-Cog.

This is where clinical experience comes in.  No drug helps everyone with a given disease.  “Only 20% of cancer patients respond long term to a type of immune checkpoint blockade (of PD-1)” Science vol. 363p. 1377 ’19.  Nonetheless immune checkpoint blockade of several types was approved by the FDA, simply because there was nothing better available.

So if nearly 2/3 of Alzheimer patients will improve at one year on Simufilam, why not  let the FDA offer it to them now under compassionate use.

 

 

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Comments

  • Anonymous  On August 4, 2022 at 11:36 am

    Lewis, thank you for writing and sharing your insightful observations. Always enjoy your writings. Please ignore a handful of the mean spirited people on Yahoo message board who are obviously shorting the stock.

    • luysii  On August 4, 2022 at 6:42 pm

      All the negative comments are ad hominem and not substantive, so there’s no point in responding. As an older and wiser doc once told me — no one wins a pissing contest

  • chase  On August 4, 2022 at 10:31 pm

    Wouldn’t compassionate use be detrimental to getting people enrolled in the P3 trials?

  • Frederick V  On August 5, 2022 at 1:43 am

    Thank you for your time analyzing simufilam and giving hope to a lot of patients that don’t have a lot of time before the decease will rob them of their cognition and loose touch to their love ones. I see this from the side where I lost my mother to this decease , and my father currently has a mild form of it. We been trying to go through steps to have our father join the phase 3 trials at cassava science. This was also the reason for me to become a Cassava Science supporter and investor. I commend you for the good work and I would forward your article to others that are interested on AD subject.

  • Ken Lipman, MD  On August 5, 2022 at 2:27 pm

    Luysii. I agree, those are very impressive open label results. To add weight to the compassionate use notion, the company has completed 50 patients in the CMS study. They are waiting to complete a total of 100. I don’t believe it would affect the blinded nature of this study for the last 50 if they compiled the results of the first 50 now. The great results for the open label study just reported make me think the results for the first 50 in the CMS study might easily reach statistical significance and lend more weight to the idea of an accelerated compassionate use approval.

  • Krishna  On August 5, 2022 at 2:43 pm

    Isn’t this new result a little worse than the original open label results?

    Last September they reported 3.2 improvement for 50 patients on the open label? Now that it is a 100 it is down to 1.5.

    Not a short — actually got into the company as a result of your writings — but I am worried the open label study is getting recruiting people with extremely mild symptoms. I think the average score was around 15?

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