Alzheimer's Drugs

What's actually true

Aduhelm was approved via the FDA's accelerated approval pathway based on amyloid plaque reduction, not clinical benefit — a surrogate endpoint. Two Phase 3 trials had been halted for futility before Biogen resurrected the drug based on a post-hoc analysis of one trial. The FDA's own advisory committee voted 10-0 against approval (with one uncertain). Medicare initially restricted coverage to clinical trials only. Biogen discontinued Aduhelm in January 2024, handing back the license. Leqembi and donanemab show statistically significant slowing of cognitive decline but the absolute benefit is small: approximately 0.45 points on the 18-point CDR-SB scale over 18 months — less than what clinicians consider the minimum clinically important difference. These drugs carry risk of ARIA (amyloid-related imaging abnormalities), essentially brain swelling or microhemorrhages, occurring in 12-36% of patients. Three patients died during lecanemab's Phase 3 trial from brain hemorrhages while on blood thinners. The amyloid hypothesis itself remains contested — amyloid removal has now been demonstrated in multiple trials with only modest-to-minimal cognitive benefit, raising fundamental questions about whether amyloid is the right target.