Donanemab Receives CHMP Positive Opinion as Treatment for Early Symptomatic Alzheimer Disease

Patrik Jonsson, executive vice president and president of Lilly International

Eli Lilly and Company recently announced that the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion recommending donanemab (Kisunla, Lilly) 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 recommendation will now move forward to the European Commission for a final regulatory decision.¹

Earlier this year, the CHMP originally refused to grant marketing authorization, citing safety concerns related to amyloid-related imaging abnormalities (ARIA), which occurred in 36.8% of treated patients in the pivotal phase 3 trial that led to the drug’s approval. For comparison, only 14.9% of those on placebo experienced ARIA. In the re-evaluation, new subgroup data showed that the risk of ARIA was significantly lower in APOE4 non-carriers and heterozygotes (33%) compared with homozygous carriers (55.9%), leading to a revised approval recommendation for these lower-risk populations.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 a statement.¹ “Donanemab has the potential to make a meaningful difference for people living with early symptomatic Alzheimer disease.”

The CHMP’s recommendation is based on data from the phase 3 TRAILBLAZER-ALZ 2 trial (NCT04437511), a randomized, placebo-controlled study evaluating donanemab in patients with early symptomatic AD confirmed by amyloid PET imaging. In the study, monthly donanemab infusions led to rapid clearance of amyloid plaque and significantly slowed cognitive and functional decline, as measured by ADAS-Cog14 and CDR-SB. The trial also demonstrated benefit in preserving daily functioning and delaying clinical disease progression.^1,2

In addition to TRAILBLAZER-ALZ 2, data from the TRAILBLAZER-ALZ 6 study (NCT05738486), which evaluated a gradual titration schedule designed to reduce ARIA risk, factored into the CHMP’s decision. This approach not only lowered the incidence of ARIA-E, but also maintained good efficacy, including amyloid clearance and plasma phosphorylated (p-tau)217 reduction. These findings contributed to the CHMP’s re-evaluation, which incorporated additional safety measures such as stricter eligibility criteria, enhanced patient monitoring, and protocols for earlier treatment discontinuation. The reassessment also reflected input from expert advisors and advocacy groups who emphasized the need for early-intervention therapies in AD.³

AD affects approximately 6.9 million people across Europe, and is expected to nearly double by 2050. Currently, around one-third of individuals with mild cognitive impairment or mild dementia due to AD progress to more advanced stages within 1 year. If approved by the European Commission, donanemab would offer a new treatment option for eligible patients in the EU to potentially slow disease progression and extend quality of life in the early stages of AD.¹

REFERENCES:
1.Lilly E. Donanemab receives positive opinion from the Committee for Medicinal Products for Human Use (CHMP) in early symptomatic Alzheimer’s disease. Prnewswire.com. Published July 25, 2025. Accessed August 5, 2025. https://www.prnewswire.com/news-releases/donanemab-receives-positive-opinion-from-the-committee-for-medicinal-products-for-human-use-chmp-in-early-symptomatic-alzheimers-disease-302513883.html
2.Rao A, Weisman D. Donanemab for Treatment of Alzheimer’s Disease. Neurology live. Published May 19, 2025. Accessed August 5, 2025. https://www.neurologylive.com/view/donanemab-for-treatment-of-alzheimer-s-disease
3.Kisunla | European Medicines Agency (EMA). European Medicines Agency (EMA). Published March 28, 2025. https://www.ema.europa.eu/en/medicines/human/EPAR/kisunla