Latest Alzheimer’s drug shown less effective in females than males

Since becoming only the second Alzheimer’s-modifying drug to gain American Federal Drug Administration 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% overall, yet one subset of data suggested little to no benefit in females, though the cause of the difference was not clear. 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.

To test whether the lecanemab trial truly showed a sex difference in drug effectiveness, McGill Ph.D. 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.

The findings are published in the journal Alzheimer’s & Dementia.

In some patients, lecanemab causes serious side effects. The findings of Andrews, Collins, and their colleagues 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.

Since becoming only the second Alzheimer’s-modifying drug to gain American Federal Drug Administration 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% overall, yet one subset of data suggested little to no benefit in females, though the cause of the difference was not clear. 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.

To test whether the lecanemab trial truly showed a sex difference in drug effectiveness, McGill Ph.D. 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.

The findings are published in the journal Alzheimer’s & Dementia.

In some patients, lecanemab causes serious side effects. The findings of Andrews, Collins, and their colleagues 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.