Real-World Leqembi Use Shows Comparable Safety to Clinical Trials
Key Insights
Real-world data from the U.S. shows lecanemab's ARIA (search) rates are consistent with clinical trials, despite a broader patient population with more comorbidities.
In Japan, lecanemab use is growing rapidly, with ARIA (search) rates half those observed in the U.S., mirroring findings from the Phase 3 Clarity trial.
Excluding APOE4 (search) homozygotes from lecanemab treatment may improve cognitive outcomes and reduce ARIA (search) risk, influencing EMA's recommendation for approval.
Lecanemab, an anti-amyloid antibody, has been in clinical use in the U.S. for nearly two years and in Japan for almost a year. Recent data presented at the Clinical Trials on Alzheimer’s Disease (search) (CTAD) conference in Madrid, Spain, offers insights into its real-world performance, revealing that ARIA (search) (Amyloid-Related Imaging Abnormalities) rates are comparable to those observed in clinical trials, despite the broader patient population with more underlying health conditions.
U.S. Experience: Consistent ARIA Rates
Marwan Sabbagh of the Barrow Neurological Institute presented administrative claims data from the Komodo Health research database, covering January 2023 through June 2024. The analysis included 3,155 patients who received at least one lecanemab infusion. The data indicated that 84% were non-Hispanic white, 93% lived in urban areas, and the average age was 75, with 56% being women. Sixty percent were diagnosed with mild cognitive impairment (search) (MCI). Notably, 4% were taking anticoagulants, a known risk factor for more serious side effects.
Sabbagh noted that lecanemab is being used appropriately, with 85% of patients continuing treatment at their four-month follow-up appointments. Lawrence Honig of Columbia University reported that among 162 patients, 11% developed ARIA (search)-E, similar to the Clarity trial rate. ARIA-E was typically mild and asymptomatic, with only one person discontinuing treatment due to ARIA-E and two due to ARIA-H. Honig emphasized that ARIA was manageable, even in patients with more co-morbidities than trial participants.
Japanese Experience: Lower ARIA Rates
In Japan, lecanemab use is climbing faster, with approximately 4,500 people currently on the drug. Takeshi Iwatsubo of the University of Tokyo reported that ARIA (search) rates in Japan are half those in the U.S., consistent with the Phase 3 Clarity trial. Lecanemab use is restricted to major medical centers capable of managing the multiple needs of patients, including MRI monitoring. APOE genotyping is required but not covered by insurance, necessitating patient enrollment in a registry maintained by academic centers.
Impact of APOE4 Genotype
Richard Perry of Imperial College London, in collaboration with Eisai scientists, analyzed the Clarity trial data, excluding APOE4 (search) homozygotes. The results indicated that amyloid removal remained the same, but cognitive outcomes improved, with decline on the CDR-SB slowed by 33% compared to 27% in the full cohort. ARIA (search)-E decreased from 13% to 9%, and ARIA-H from 17% to 13%. The EMA's CHMP committee cited this analysis in its reconsideration, recommending approval of lecanemab, except for APOE4 homozygotes.
Challenges and Future Directions
Despite the promising data, challenges remain. In the U.K., the National Health Service will not cover the cost of lecanemab, limiting access. In Japan, only a small proportion of the estimated one million eligible individuals will be able to receive treatment due to the limited number of licensed physicians and infusion sites. These findings underscore the need for more treatment options and improved access to care for Alzheimer's disease patients.