Eli Lilly’s Anti-Amyloid Therapy Donanemab Gains EU Approval for Alzheimer Disease

More than a year after the donanemab (Kisulna; Eli Lilly) gained FDA approval for the treatment of early symptomatic Alzheimer disease (AD), the European Commission announced the approval of the anti-amyloid treatment, further broadening the treatment’s reach.¹

Donanemab, a once-monthly treatment, is indicated for those with mild cognitive impairment (MCI) and mild dementia stages of AD with confirmed amyloid pathology who are apolipoprotein E (APOE4) heterozygotes or non-carriers. The EU’s marketing authorization for the medication was based on data from the phase 3 TRAILBLAZER-ALZ 2 trial (NCT04437511), which supported its original FDA approval, as well as TRAILBLAZER-ALZ 6 (NCT05738486), which demonstrated the effectiveness of a modified titration dosing regimen.

Similar to its approval in America, donanemab’s label comes with a risk for amyloid-related imaging abnormalities (ARIA). Patients who receive the therapy in Europe will also go by the newly recommended titration dosing schedule, which calls for a more gradual administration of the drug. For context, the FDA approved an update to donanemab’s labeling in July to include this new dosing regimen, which lowers the risk of ARIA while maintaining the drug’s effect on amyloid plaque removal and phosphorylated tau 217 reduction.²

"Kisunla demonstrated meaningful results in people with early symptomatic Alzheimer's disease by significantly slowing cognitive and functional decline in our Phase 3 TRAILBLAZER-ALZ 2 study," Patrik Jonsson, executive vice president and president of Lilly International, said in a statement.¹ “The data shows that the earlier patients are identified, diagnosed, and treated with Kisunla, the greater the response to treatment. This authorization brings a new option to patients in Europe—offering hope and the potential for more time to focus on what matters most."

Donanemab, approved in the U.S. in 2023, became the second known anti-amyloid drug on market, behind Eisai’s lecanemab (Leqembi). Donanemab is built to target amyloid-ß plaques containing pyroglutamate, which are thought to be more resistant to breakdown and play a role in plaque seeding. This medication comes with a limitation duration strategy, as treatment may be stopped once amyloid PET scans show clearance below a set threshold.

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Earlier this year, the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) originally refused to grant marketing authorization, citing safety concerns related to the drug’s ARIA risk, which occurred in 36.8% of treated patients in TRAILBLAZER-ALZ 2. Months later, the agency changed course, issuing a positive opinion or recommendation for approval.³

The CHMP’s re-evaluation, which incorporated additional safety measures such as stricter eligibility criteria, enhanced patient monitoring, and protocols for earlier treatment discontinuation, was helped by the published data from TRAILBLAZER-ALZ 6. The study, a double-blind, phase 3b trial, compared the standard donanemab dosing regimen to 3 alternative dosing arms.⁴

All told, TRAILBLAZER-ALZ 6 met its primary end point, with those in the modified treatment arm demonstrating lowered ARIA-Edema relative risk reduction (RRR) over a 24-week period compared with standard dosing. Overall, the ARIA-E frequency was 13.7% in the modified titration arm compared with 23.7% in the standard arm at that time point, which remained consistent out to 52 weeks. Notably, only the modified titration arm met the primary objective with a posterior risk reduction and a 94.1% probability that the RRR was at least 20%.

The modified titration arm demonstrated a clear advantage in reducing ARIA-E severity, with significantly lower radiographic severity at 24 weeks (P = .011) and 86.3% of participants showing no ARIA-E compared with 76.3% in the standard arm, with no severe cases reported. Across APOE ε4 genotypes, ARIA-E was numerically less frequent in the modified arm, most notably among homozygous carriers, where rates dropped from 57.1% with standard titration to 19.0% with modified dosing.

In TRAILBLAZER-ALZ 6, symptomatic ARIA-E was also reduced, occurring in 4.8%, 8.0%, and 0% of homozygous, heterozygous, and non-carrier participants in the standard arm versus 0%, 3.5%, and 2.7%, respectively, with the modified approach. Overall, these findings suggest that modified titration not only improves ARIA-E outcomes but may also mitigate genotype-related risk.

REFERENCES
1. Lilly's Kisunla (donanemab) receives marketing authorization by European Commission for the treatment of early symptomatic Alzheimer's disease. News release. Eli Lilly. September 25, 2025. Accessed September 30, 2025. https://www.prnewswire.com/news-releases/lillys-kisunla-donanemab-receives-marketing-authorization-by-european-commission-for-the-treatment-of-early-symptomatic-alzheimers-disease-302567710.html
2. FDA approves updated label for Lilly's Kisunla (donanemab-azbt) with new dosing in early symptomatic Alzheimer's disease. News release. Eli Lilly. July 9, 2025. Accessed September 30, 2025. https://investor.lilly.com/news-releases/news-release-details/fda-approves-updated-label-lillys-kisunla-donanemab-azbt-ne
3. 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 September 30, 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
4. Wang H, Serap E, Nery M, et al. Modified titration of donanemab reduces ARIA risk and maintains amyloid reduction. Alzheimer & Dement. Published online April 2, 2025. doi:10.1002/alz.70062