Tag Archives: FDA advisory committee

What controls should Cassava Sciences use for their open label trial?

MDs gradually woke up to the fallacy of using historical rather than concurrent controls particularly in studies of therapies to prevent heart attack and stroke, as the rates of both dropped significantly in the past 50 years, and survival from individual heart attacks and strokes also improved.

An open label trial is just that, no placebo, no controls.  Such trials are done in the exploratory phase of drug development to look for side effects and (hopefully) therapeutic effects.

Cassava Sciences has been attacked because their open label study of Simufilam had no controls.  Duh !

Here is a suggestion for the concurrent controls for the Cassava study:  the Biogen study leading to approval of aducanumab (Aduhelm).  It’s a little hard to find out exactly when it was done, but it certainly was within the past 10 years. Here is a link to an article on Alzheimer therapy from Science — https://science.sciencemag.org/content/sci/373/6555/624.full.pdf

Cassava’s work is nowhere to be found.  The article contains the following

“Although the marked decrease in amyloid deposits can be viewed as biological evidence of disease modification, this was accompanied by a decidedly mixed outcome on cognitive testing, with one aducanumab trial (EMERGE, NCT02484547) meeting its prespecified primary and secondary endpoints at the highest dose, whereas the other (ENGAGE, NCT02477800) did not achieve them.”

So use Biogen’s data on aducanumab as the placebo control (which I and the FDA advisory committee think it is).  There is a reason the entire committee resigned after the FDA approved the drug.