EMA Advisory Group Issues Positive Opinion on Lilly's Donanemab for Treatment of Early Alzheimer Disease

Eli Lilly’s anti-amyloid therapy donanemab received a positive opinion from the European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) for the treatment of early symptomatic Alzheimer disease (AD) in adults with confirmed amyloid pathology who are apolipoprotein E ε4 (ApoE4) heterozygotes or non-carriers. The European Commission is expected to make a final regulatory decision in the coming months, according to the company's July 25 announcement.¹

In Europe, where AD currently affects up to 6.9 million adults, the prevalence is expected to nearly double by 2050.^2,3 Among individuals with mild cognitive impairment, approximately one-third will progress to the next clinical state of the disease within a year.³

"This positive opinion marks a significant milestone in our efforts to bring donanemab to eligible patients across Europe," Patrik Jonsson, executive vice president and president of Lilly International, said in the statement. "Donanemab has the potential to make a meaningful difference for people living with early symptomatic Alzheimer's disease, and Lilly remains committed to advancing the science through ongoing clinical trials and programs."¹

The data supporting the CHMP's positive nod is primarily from the TRAILBLAZER-ALZ-2 clinical trial, in which donanemab significantly retarded cognitive and functional decline by up to 35% in participants with less advanced disease over 18 months compared with placebo and reduced disease progression by 37%.⁴

The committee also considered findings from the TRAILBLAZER-ALZ-6 clinical trial,⁵ which evaluated a modified titration dosing schedule for donanemab to mitigate the risk of amyloid-related imaging abnormalities (ARIA), a type of adverse event associated with the class of anti-amyloid therapies. Although ARIA rarely cause symptoms, they can occur and be serious and life-threatening. The updated regimen, which redistributes dosing across the first 3 infusions, led to a 41% reduction in ARIA with edema/effusion at 24 weeks (14% vs 24%) and a 35% reduction at 52 weeks (16% vs 25%) compared with the original schedule. There was no observed effect on donanemab efficacy, with similar reductions in amyloid plaque and plasma P-tau217 levels between the original and revised dosing arms. The US FDA recently expanded the drug's labeling to include the new titration schedule. (Syd)

Donanemab (marketed as Kisunla in the US), was approved by the FDA in July 2024 for the treatment of adults with early symptomatic AD, including individuals with mild cognitive impairment or mild dementia due to AD, confirmed by amyloid pathology. Unlike previous anti-amyloid monoclonal antibodies, donanemab is the first with evidence to support limited-duration therapy guided by amyloid plaque clearance. In the phase 3 TRAILBLAZER-ALZ-2 trial, nearly half of participants were able to complete treatment within 12 months. Donanemab reduced amyloid plaques by 61% at 6 months, 81% at 12 months, and 84% at 18 months. Once minimal plaque levels were achieved, confirmed by amyloid PET, participants transitioned to placebo for the remainder of the study.

In addition to the US, donanemab is currently available in several international markets, including Japan, China, the United Kingdom, Brazil, and Australia.

References

1. Donanemab receives positive opinion from the Committee for Medicinal Products for Human Use (CHMP) in early symptomatic Alzheimer's disease. News release. Eli Lilly and Company. July 25, 2025. Accessed July 25, 2025.

2. Gustavsson A, Norton N, Fast T, et al. Global estimates on the number of persons across the Alzheimer's disease continuum. Alz Dement. 2023;19:658-670. doi:10.1002/alz.12694

3. Prevalence of dementia in Europe. Alzheimer Europe. Accessed July 25, 2025. https://www.alzheimer-europe.org/dementia/prevalence-dementia-europe

4. Halsey G. Lilly's donanemab approved by FDA for treatment of early symptomatic AD. Patient Care. July 2, 2024. https://www.patientcareonline.com/view/lilly-s-donanemab-approved-by-fda-for-treatment-of-early-symptomatic-ad

5. Jennings S. Modified donanemab dosing reduces ARIA-E in adults with early symptomatic Alzheimer disease. Patient Care. October 30, 2024. https://www.patientcareonline.com/view/modified-donanemab-dosing-reduces-aria-e-in-adults-with-early-symptomatic-alzheimer-disease