The European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) has issued a positive recommendation for Eisai and Biogen's Leqembi (lecanemab) as a treatment for Alzheimer's disease, but only for a specific subset of patients. This decision marks a reversal from the committee's initial rejection in July 2024, which cited concerns over the drug's safety and efficacy. The recommendation now applies exclusively to patients with mild cognitive impairment or mild dementia due to Alzheimer's who carry one or no copies of the ApoE4 gene variant.
Revised Recommendation Based on Subgroup Analysis
The CHMP's initial negative opinion stemmed from worries about amyloid-related imaging abnormalities (ARIA), indicative of brain swelling, fluid buildup, or bleeding, observed in MRI scans. The committee also questioned whether Leqembi's effect on delaying cognitive decline was substantial enough to outweigh these risks in a broad patient population. However, after a re-examination requested by Eisai and Biogen, the CHMP revised its stance based on new subgroup analyses that excluded data from patients with two copies of ApoE4, who are at the highest risk of ARIA.
Data from patients treated with Leqembi who had one or no copies of ApoE4 showed a lower incidence of ARIA-E (brain swelling), at 8.9%, compared to 12.6% in the broader patient group. Similarly, ARIA-H (brain bleeding) was observed in 12.9% of the restricted group, versus 16.9% of all patients. For comparison, placebo-treated patients in the restricted group experienced ARIA-E and ARIA-H at rates of 1.3% and 6.8%, respectively.
Controlled Access and Monitoring
The EMA is expected to make a final decision on Leqembi's marketing authorization in January 2025. To mitigate risk, the EMA plans to implement a controlled access program, restricting use to the recommended patient group. This program will include mandatory magnetic resonance imaging (MRI) scans to monitor for ARIA before treatment initiation and before the 5th, 7th, and 14th doses, with additional scans if symptoms arise.
Leqembi's Mechanism and Market Context
Leqembi targets amyloid plaques in the brain, a hallmark of Alzheimer's disease believed to impair memory and cognition. The drug received accelerated approval from the US FDA in January 2023, later converted to full approval in July 2023. Despite these approvals, Eisai recently adjusted its sales forecast for Leqembi, lowering it by $90 million to $280 million for the second half of the 2024 fiscal year, citing delays in US revenue.
Alzheimer's Disease Burden
The number of people with Alzheimer's in the eight major markets (US, France, Germany, Italy, Spain, UK, Japan, and China) is projected to increase from 21,921,200 in 2020 to 29,898,812 in 2030, according to GlobalData.
