FDA Grants Full Approval to Donanemab for Alzheimer's Disease: Amyloid Plaque Reduction Up to 84% in 2026

What Is Donanemab and How Does It Treat Alzheimer's Disease?

Donanemab (brand name Kisunla), developed by Eli Lilly, is a humanized IgG1 monoclonal antibody that specifically targets N3pG-modified amyloid-beta, a form of amyloid plaque found predominantly in established brain deposits. Unlike lecanemab, which targets soluble amyloid protofibrils, donanemab binds to deposited plaques and facilitates their clearance through microglial phagocytosis. The drug is administered as an intravenous infusion every four weeks.

The pivotal TRAILBLAZER-ALZ 2 trial, published in JAMA in 2023, enrolled 1,736 participants with early symptomatic Alzheimer's disease and confirmed amyloid pathology via PET imaging. Results demonstrated that approximately 84% of participants achieved amyloid plaque clearance to near-normal levels within 12 months of treatment, with about 52% of patients able to discontinue treatment after achieving clearance — a unique feature among anti-amyloid therapies. Longer-term follow-up data supporting sustained clinical benefit contributed to the FDA's decision to grant full traditional approval.

How Effective Is Donanemab Compared to Other Alzheimer's Treatments?

In the combined low/medium tau population of the TRAILBLAZER-ALZ 2 trial, donanemab slowed decline on the integrated Alzheimer's Disease Rating Scale (iADRS) by 35% and on the Clinical Dementia Rating–Sum of Boxes (CDR-SB) by 36% compared to placebo over 76 weeks. For patients in the low tau subgroup — representing earlier-stage disease — the benefit was even more pronounced, with approximately 40% slower decline on iADRS. Head-to-head comparisons with lecanemab are not available, but indirect analysis suggests comparable or slightly greater clinical benefit.

The most significant differentiator is donanemab's time-limited dosing regimen. Because treatment can be stopped once amyloid plaques are cleared, the average treatment duration is approximately 12 months, compared to lecanemab's indefinite biweekly infusions. This translates to lower lifetime treatment costs and reduced patient burden. However, ARIA (amyloid-related imaging abnormalities) occurred in approximately 24% of donanemab-treated patients, with symptomatic ARIA-E (edema) reported in about 6% of cases. The FDA label requires regular MRI monitoring during and after treatment.

What Does Full FDA Approval Mean for Patient Access?

The transition from accelerated to full traditional approval is expected to significantly expand patient access. Under accelerated approval, the Centers for Medicare and Medicaid Services (CMS) had imposed a coverage with evidence development (CED) requirement, limiting Medicare reimbursement to patients enrolled in qualifying clinical registries — a framework previously applied to lecanemab. With full approval, CMS is expected to issue a revised National Coverage Determination removing the registry requirement and allowing standard Part B coverage for eligible patients, as it did when lecanemab received full approval in 2023.

Eli Lilly set the wholesale acquisition cost at approximately $32,000 per year of treatment when Kisunla first launched in 2024. The time-limited dosing regimen potentially reduces total per-patient treatment costs compared to indefinite therapies. Major private insurers are expected to broaden coverage following full approval. The Alzheimer's Association estimates that over 6.9 million Americans are living with Alzheimer's disease, though the number eligible for anti-amyloid therapy is considerably smaller, limited to those with early symptomatic disease and confirmed amyloid pathology.