On 24 May, a group of clinical and research experts led by Bart De Strooper (University College London, United Kingdom) and Henrik Zetterberg (University of Gothenburg, Sweden) published a letter in The Lancet journal, entitled “The regulatory rollercoaster continues—EMA refuses donanemab”. In the article, the authors review the recent decision by the European Medicines Agency (EMA) not to approve donanemab, an anti-amyloid monoclonal antibody for the treatment of early Alzheimer’s disease. This decision follows the EMA’s earlier approval of lecanemab, a similar therapy, in early 2025 after a prolonged regulatory review. The authors note that donanemab has already been approved in several countries outside Europe, based on evidence from trials such as TRAILBLAZER-ALZ 2 and TRAILBLAZER-ALZ 6.
The authors state that these trials demonstrated cognitive benefits comparable to those seen with lecanemab, as well as swift amyloid clearance. They also cite similar safety profiles between the two drugs, including rates of amyloid-related imaging abnormalities (ARIA) and related adverse events. They note the need for further clarification on the impact of cerebrovascular vulnerability on ARIA risk for patients receiving donanemab, suggesting that a contraindication for individuals with superficial siderosis (indicative of cerebrovascular vulnerability), improved safety monitoring and adapted dosing regimens could help minimise risk. Given the contrasting regulatory outcomes, the authors question the rationale for the EMA’s decision to reject donanemab, warning of potential consequences for access to innovation and future investment in Alzheimer’s research within Europe.
Read the letter in the Lancet: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(25)00833-5/fulltext
