McGill researchers found lecanemab may be less effective in women, prompting calls for more personalized treatment and improved consideration of sex differences in clinical trials.
Since becoming only the second Alzheimer’s-modifying drug approved by the U.S. Food and Drug Administration in 2023, lecanemab (marketed as Leqembi) has seen steadily increasing sales, reaching $87 million USD in the final quarter of 2024.
In its Phase 3 clinical trial, lecanemab was shown to slow cognitive decline by 27% overall. However, a subset of the trial data indicated little to no benefit among female participants, though the reason for this difference remains unclear. Despite this, an FDA advisory committee unanimously agreed that the Phase 3 trial confirmed the drug’s clinical benefit. Nonetheless, several follow-up studies have highlighted the sex-based discrepancy, raising questions about the drug’s effectiveness in women and sparking debate over its use in female patients.
Investigating the Sex-Based Discrepancy
To test whether the lecanemab trial truly showed a sex difference in drug effectiveness, McGill PhD candidate Daniel Andrews, in collaboration with researchers led by neuroscientist Prof. Louis Collins, ran simulated trials on openly available Alzheimer’s patient data, using the same demographics and constraints as the lecanemab trial. They found that indeed lecanemab was probably less effective in females than males in the Phase 3 trial. However, there was insufficient evidence to say the drug was totally ineffective in females.
In some patients, lecanemab causes serious side effects. Andrews’ and Collins’ findings should better prepare clinicians to decide whether the potential benefits of lecanemab outweigh the potential harms in female patients, and may inform future consideration of the drug’s approval in other countries. The findings also suggest ways future drug trials can better account for sex differences.
Reference: “The higher benefit of lecanemab in males compared to females in CLARITY AD is probably due to a real sex effect” by Daniel Andrews, Simon Ducharme, Howard Chertkow, Maria Pia Sormani and D. Louis Collins for the Alzheimer’s Disease Neuroimaging Initiative, 29 January 2025, Alzheimer’s & Dementia.
DOI: 10.1002/alz.14467
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