Why no ARIA is a slam dunk for Cassava Sciences
Even though the fat lady hasn’t sung the ARIA because there’s no ARIA to sing for Simufilam, it’s over for the monoclonals.
Only a practicing physician could see why. In the Lecanemab trial 21% had ARIA and 3% were symptomatic. In the Donanemab trial 37% had ARIA and 6% had symptoms [ Science vol. 381 pp. 466 – 467 ’23 ].
If you’re new to the game keep reading, all terms will be defined in a moment. Assume for the moment, that the clinical benefit of Simufilam has been shown in the double blind trials (to be completed in 18 months) to have the same or greater benefits than the monoclonals for Alzheimer’s disease (not a difficult task).
No practicing physician would then voluntarily assume a 3 – 6% risk of having to stand in front of a malpractice jury and explain why he/she used a monoclonal antibody against aBeta peptide instead of Simufilam, which hasn’t produced any ARIA in 180 patients on the drug for a year (results released by Cassava Sciences today).
No physician ever ‘wins’ a malpractice suit, even if the jury decides in their favor. I’ve watched such suits drain the life out of colleagues and friends. No doc would ever voluntarily put their head in such a meatgrinder.
Now for a few definitions for those new to the game
ARIA means Amyloid Related Imaging Abnormalities. It is something picked up by MRI (Magnetic Resonance Imaging) and it basically means bleeding into the brain. Would you want such a thing in your brain (even if asymptomatic?).
Why does this happen, with monoclonal antibodies against the aBeta peptide? Because they remove aBeta peptide, and although aBeta is the main constituent of the senile plaque of Alzheimer’s disease, it sometimes occurs in vessels where removing it leads to weakened vessels and bleeding.
Hindsight is wonderful, but the logic behind monoclonal antibodies was impeccable. If the senile plaque of Alzheimer’s disease causes the disease (debatable) and the main constituent of the plaque is aBeta, try to remove aBeta and see if you can cure Alzheimer’s.
Why Magnetic Resonance Imaging to pick up ARIA. Because blood is full of iron which is magnetic, and blood where shouldn’t be causes all sorts of magnetic disturbances on MRI.