Eli Lilly’s donanemab became only the second FDA-approved therapy to actually modify Alzheimer’s disease progression, not just mask symptoms. The drug reduces brain plaques by 84% and slows cognitive decline by up to 35% in a finite 12-18 month treatment course, fundamentally changing what’s possible for early-stage patients.
What Donanemab Actually Does
Most earlier Alzheimer’s medications like donepezil or memantine work downstream, boosting neurotransmitter levels to temporarily prop up cognition. Donanemab operates at the source. It’s a monoclonal antibody that binds specifically to pyroglutamate-modified amyloid beta, a particularly stubborn form of the protein plaques that accumulate in Alzheimer’s-affected brains.
Once bound, the drug flags these plaques for removal by the immune system. The results from the TRAILBLAZER-ALZ 2 trial were striking: an average 84% reduction in amyloid plaques at 18 months, cognitive and functional decline slowed by up to 35% compared to placebo, and risk of progressing to the next clinical stage reduced by up to 39%.
Donanemab is designed as a finite treatment course. Patients receive monthly IV infusions, and once brain scans confirm sufficient plaque clearance, typically within 12 to 18 months, treatment stops. This contrasts with lecanemab, the other approved disease-modifying therapy, which requires ongoing biweekly infusions. A subgroup of treated patients maintained cognitive benefit for two years, suggesting the effects may persist beyond the active treatment window.
Who May Benefit Most
Donanemab doesn’t work for everyone. The strongest evidence supports use in people with mild cognitive impairment or early-stage Alzheimer’s dementia who have confirmed amyloid plaques. Verification comes through PET imaging or cerebrospinal fluid testing. In the TRAILBLAZER-ALZ 2 trial, patients with low-to-intermediate levels of tau pathology showed substantially better outcomes than those with advanced tau burden.
Early detection dramatically shapes eligibility and potential benefit. By the time Alzheimer’s reaches moderate or advanced stages, neuronal damage has progressed beyond what plaque removal alone can meaningfully address.
The primary risk is ARIA, which includes brain swelling or microbleeds detectable on MRI. A modified dosing schedule reduced ARIA-E incidence by 41% compared to the original regimen. Still, regular MRI monitoring remains necessary during treatment. Donanemab carries an estimated annual cost of approximately $32,000, covered by Medicare with prior authorization requirements.
