Why the results of the open label trial of Simufilam will be misinterpreted

Cassava Sciences said they will release the results of the 200 person open label trial this year.  I think the results are likely to be misunderstood.

First: a disclaimer.  I have no inside information about the results of the trial.  I have known Lindsay Burns since she was in high school, as my wife and I were friendly with her parents when I practiced neurology in Montana.  Lindsay comes from smart .people, father Horatio went through Harvard in under 4 years getting a degree in physics.

Lindsay and I have been contact for over 10 years, mostly concerning the science behind Alzheimer’s disease and Simufilam,.  We do schmooze a bit about Montana and our time there and the vituperation she and Cassava Sciences have been exposed to.

Lindsay and I are well aware about the use of inside information, particularly since both of my wife’s parents had lifelong careers at the SEC, beginning in the depression.

Let’s assume that the results in the open label trial on 200 patients for 1 year are similar to those released in August of 2021 on the first 50 patients in the study to have been on Simulfilam for 9 months.

10% of the patients likely had at least a 50% improvement in their ADAS-Cog-11 score, and over 50% had some improvement.  Some, of course got worse, so the overall improvement of the group  at 9 months as a whole was slight but real.

Let’s say the results on the whole 200 are similar, with 20 or so patients showing similar 50% improvement, but the group overall showing only slight improvement.

These results, even though open label and unblinded, would be unprecedented.  People with Alzheimer’s have good and bad days, but NONE are better after a year.  Throw in all the studies with monoclonal antibodies against aBeta, and you won’t see results like this.  The best they have to offer is a slightly slower (25 – 50%) rate of decline.  This is also true for the demented patients I saw in over 30 years of clinical practice.  So even though the study is open label, we have a ton of controls outside the study.

Even if Simufilam significantly helps 10% of those receiving it, these are results worth having and should lead to early adoption of Simufilam

6 months down the road the Cognition Maintenance Study (which is blinded and placebo controlled) should give a more definitive answer, leading to early adoption.

Here is a link to a more lengthy analysis of the first 50 cases to go 9 months

Cassava Sciences 9 month data is probably better than they realize

Here is a link to a description of the Cognition Maintenance study

Cassava’s Cognition Maintenance Study may prove Simufilam works