Since becoming only the second Alzheimer’s-modifying drug to gain American FDA approval in 2023, sales of lecanemab, known by its brand name Leqembi, have risen steadily, reaching $87-million USD in the last quarter of 2024.
In its Phase 3 clinical trial, lecanemab slowed cognitive decline by 27 per cent overall. An FDA committee voted unanimously that the Phrase 3 trial verified the clinical benefit of lecanemab. Even so, several follow-up papers focused on the trial’s apparent sex difference result to cast doubt on prescribing lecanemab to females. The cause of the difference was not clear.
What was clear are the following points:
- The CLARITY AD Trial showed a 31% sex difference in lecanemab’s effect.
- This implies lecanemab is more clinically effective in males than in females.
- A sex difference in lecanemab’s efficacy could be linked to its action mechanism.
Simulated Trials
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 Louis Collins, PhD, 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 Prof. 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, including Canada. The findings also suggest ways future drug trials can better account for sex differences.
