Leqembi's EU Approval Faces Further Delay as EMA Re-evaluates Safety Data
Key Insights
The European Commission has requested the EMA to re-examine Leqembi's safety data, potentially delaying its EU approval beyond the expected timeframe.
The CHMP will assess recent safety data to determine if an update to its positive opinion is needed, particularly regarding risk minimization measures.
Eisai and Biogen believe existing data support Leqembi's safety profile, reinforced by clinical use in the US and other approved regions.
The European approval of Leqembi (lecanemab), an Alzheimer's disease (search) therapy developed by Eisai and Biogen, has been delayed as the European Commission has requested the European Medicines Agency (EMA) to re-evaluate recent safety data. This development introduces a new hurdle in the path to making the drug available to patients in the European Union.
The EMA's human medicines committee, the CHMP, has been asked to review up-to-date safety data on Leqembi at its next meeting in February. The request follows the CHMP's initial rejection of Leqembi in July 2024, which was based on concerns that the risk of serious side effects outweighed the drug's modest efficacy in delaying cognitive decline. Although the CHMP revised its opinion in November, recommending approval for a subgroup of patients with one or no copies of the ApoE4 (search) gene, the European Commission's intervention has put the final decision on hold.
The CHMP will now consider safety data generated since its latest opinion and assess "whether this may require an update of the opinion, and to consider whether the wording of the risk minimisation measures in the opinion is clear enough to ensure correct implementation." Patients with one or no copies of ApoE4 (search) are less likely to experience side effects like brain swelling (ARIA-E) and brain bleeding (ARIA-H) associated with amyloid-targeting drugs like Leqembi than people with two ApoE4 copies.
Eisai and Biogen have expressed confidence in Leqembi's safety profile, citing clinical practice in the US and other countries where the drug has already been introduced. In a statement, the companies said they believe the European Commission's requests can be addressed with existing information and will be evaluated by the CHMP because of the clear and sufficient information available. They added that they will continue to work closely with the authorities toward approval in the EU.
Clinical Trial Data and Regulatory Considerations
European regulators previously examined data to assess whether excluding patients with two copies of ApoE4 (search) would substantially reduce ARIA rates. Clinical trial data indicated that overall, one in eight participants developed brain swelling (ARIA-E), and about one in six developed brain bleeds (ARIA-H). However, in the subpopulation with zero or one copy of ApoE4, ARIA-E rates dropped to one in 11, and ARIA-H rates dropped to one in eight.
The Leqembi clinical trial measured disease progression using an 18-point dementia scale over 18 months. Participants in the placebo group declined by 1.66 points, while those receiving the drug declined by 1.21 points, representing a relative slowing of cognitive decline by 27 percent (0.45 points difference).
Global Approvals and Post-Market Monitoring
Leqembi has already been approved in the US, Japan, China, South Korea, Hong Kong, Israel, and the UAE, with varying restrictions based on ApoE4 (search) status. In the US, Eisai and Biogen recently received approval for a new once-monthly intravenous maintenance dose of Leqembi, following an initial biweekly IV induction course. This new regimen aims to reduce the frequency of clinic visits for patients.
If approved in the EU, Eisai will be required to conduct a safety study to further assess the risk of ARIA-E and ARIA-H and establish an EU-wide database to track side effects, the long-term impact of ARIA, and the effectiveness of Leqembi in slowing disease progression over time. The Alzheimer's Association has sponsored a voluntary database called ALZ-NET in the U.S. to track similar information.