The European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion recommending marketing approval for Leqembi (lecanemab) for the treatment of early Alzheimer's disease. This decision marks a significant turnaround after the CHMP initially rejected the drug in July 2024 due to concerns over the risk of amyloid-related imaging abnormalities (ARIA), a side effect characterized by brain swelling and microbleeding. The recommendation is specifically for adult patients with mild cognitive impairment or mild dementia due to Alzheimer's disease who are apolipoprotein E ε4 (ApoE ε4) non-carriers or heterozygotes with confirmed amyloid pathology. A final decision from the European Commission is expected within 67 days. Eisai leads the clinical development and regulatory submissions for Leqembi, in collaboration with Biogen.
Restriction to Specific Genetic Profile
The CHMP's positive opinion is contingent upon restricting Leqembi's use to patients with one or no copies of the ApoE ε4 gene, a genetic profile that Jefferies analyst Michael Yee estimates represents 60% to 80% of the Alzheimer's population in Europe. This restriction is based on clinical data indicating lower rates of ARIA in this subgroup. Specifically, among patients with one or no copies of the risk gene who received Leqembi, nearly 9% experienced brain swelling and 13% experienced microbleeding, compared to 1.3% and 6.8% in the placebo group, respectively. In contrast, among all participants who received Leqembi, the rates of ARIA brain swelling and microbleeding were 12.6% and 16.9%.
Clinical Efficacy and Safety Monitoring
The CHMP emphasized that the benefits of Leqembi in the restricted population align with those observed in the broader population studied in clinical trials. The approval recommendation includes a caveat that measures be implemented to mitigate the risk of severe and symptomatic ARIA and to monitor its long-term consequences. Leqembi's efficacy in slowing the progression of Alzheimer's by approximately 27% has been described as modest by some experts.
Commercial Implications and Market Dynamics
Analysts anticipate that even with the restricted approval, Leqembi could significantly boost sales for Eisai and Biogen. RBC analyst Brian Abrahams estimates peak annual Leqembi sales could reach $8.3 billion, with 20% originating from the European market. Eisai reported $66 million in Leqembi revenue between July and September 2024, and Biogen anticipates improved financial performance due to the drug's increasing sales. However, Piper Sandler analyst Christopher Raymond suggests that Eisai and Biogen may face commercial challenges similar to those encountered in the U.S., which have resulted in relatively slow uptake. The drug's price in Europe is expected to be lower than its U.S. price of approximately $11,000 per patient.
Competition in the Alzheimer's Disease Market
Leqembi is designed to target and break down amyloid beta plaques, which are believed to be a root cause of Alzheimer's disease. Eli Lilly's Kisunla (donanemab), another recently approved anti-amyloid antibody, is also a competitor in the Alzheimer's disease market. Prothena is developing PRX012, a next-generation subcutaneous antibody, targeting a key epitope at the N-terminus of Aβ. PRX012 is in early-stage development. Prothena is also developing a dual Aβ-Tau vaccine, PRX123, a potential prevention and treatment for AD.
