The promising Alzheimer's drug that the US has approved (but the EU has not) reduces its adverse effects.

Eli Lilly today announced that the U.S. Food and Drug Administration ( FDA ) has approved a label update recommending a dosage adjustment for donanemab , Lilly’s once-monthly anti-amyloid therapy for the treatment of adults with early symptomatic Alzheimer’s disease — people with mild cognitive impairment or mild dementia due to Alzheimer’s disease with established brain amyloid pathology1,2. In the TRAILBLAZER-ALZ 6 study, the titration significantly reduced the incidence of amyloid-related imaging abnormalities with edema/effusion ( ARIA-E ) versus the original regimen at 24 and 52 weeks, achieving similar levels of amyloid plaque clearance and P-tau reduction217 .

"We are confident that this update to the donanemab label will greatly assist healthcare professionals in evaluating the most appropriate treatment options for their patients," said Brandy Matthews, MD , vice president of Alzheimer's Disease Medical Affairs for Lilly Global and U.S. "This label update underscores our strong commitment to patient safety and advancing the treatment of Alzheimer's disease by potentially mitigating the risk of ARIA-E ."

The new regimen involves more gradual dosing , and the TRAILBLAZER-ALZ 6 study demonstrated a significant reduction in the incidence of ARIA-E by 41% at 24 weeks and 35% at 52 weeks compared with the original regimen. ARIA-E is an adverse effect of therapies targeting amyloid plaques , including donanemab. ARIA is generally asymptomatic, although serious and even fatal adverse events can occur. The new dosing regimen differs from the original regimen in that one of the two vials from the first dose is shifted to the third dose, with the same total amount of donanemab administered before week 24. This change resulted in lower rates of ARIA-E without compromising donanemab’s ability to clear amyloid plaques or the potentially time-limited monthly dosing of a treatment that reduces amyloid plaques to minimal levels.3-6

Key findings from the TRAILBLAZER-ALZ 6 study that support this SmPC update:The primary endpoint of the study was the proportion of participants with at least one ARIA-E event by week 24. Results showed that the incidence of ARIA-E was 14% in patients on the new dosing regimen versus 24% with the original regimen, a 41% relative risk reduction . 7 At week 52, the rates were 16% and 25%, respectively, with a 35% relative risk reduction. Asymptomatic ARIA events observed at week 52 included total ARIA, ARIA-E, and ARIA-H in 29%, 16%, and 25% of patients on the new dosing regimen, respectively. ARIA-E and ARIA-H are different types of amyloid-related imaging abnormalities (ARIA). ARIA with edema is called ARIA-E and ARIA with hemorrhage or hemosiderin deposition is called ARIA-H.

Patients on the new dosing regimen experienced reductions in amyloid plaque and P-tau217 comparable to those on the original regimen. As observed by amyloid PET in the 24-week primary endpoint of the TRAILBLAZER-ALZ 6 study, patients on the new donanemab dosing regimen reduced their amyloid plaque levels by an average of 67% from baseline, compared with 69% in patients on the original dosing regimen.

No new adverse reactions were identified in this study, although higher rates of hypersensitivity reactions and infusion-related reactions were observed.

"This new dosing strategy represents a significant advance for patients and their caregivers," said Dr. Elly Lee, medical director and principal investigator of the Irvine Center for Clinical Research . "By significantly reducing the risk of ARIA-E , we can provide greater confidence in the safety of donanemab without compromising its efficacy in reducing amyloid plaques ."

The FDA approved donanemab in July 2024 based on data from the Phase 3 TRAILBLAZER-ALZ 2 study , which showed that donanemab significantly slowed cognitive and functional decline in less pathologically advanced patients by up to 35%, and by 22% in the overall study population, compared with placebo, at 18 months. 9 Donanemab reduced the risk of progression to the next clinical stage of the disease by 37% over the same time period. 3 Cognitive and functional decline was characterized by more severe memory and thinking problems, greater difficulties with daily activities, and greater need for help from caregivers.

In Europe, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) issued an opinion on March 27, 2025, recommending against granting marketing authorization to Lilly's donanemab for the treatment of adults with early symptomatic stages of Alzheimer's disease. Donanemab is currently undergoing re-evaluation by this regulatory body at the company's request.

Eli Lilly today announced that the U.S. Food and Drug Administration ( FDA ) has approved a label update recommending a dosage adjustment for donanemab , Lilly’s once-monthly anti-amyloid therapy for the treatment of adults with early symptomatic Alzheimer’s disease — people with mild cognitive impairment or mild dementia due to Alzheimer’s disease with established brain amyloid pathology1,2. In the TRAILBLAZER-ALZ 6 study, the titration significantly reduced the incidence of amyloid-related imaging abnormalities with edema/effusion ( ARIA-E ) versus the original regimen at 24 and 52 weeks, achieving similar levels of amyloid plaque clearance and P-tau reduction217 .