Eisai has announced new 36-month (3-year) efficacy and safety results from its Phase 3 Clarity AD core study and open-label extension (OLE) for its anti-amyloid therapy lecanemab (commercially Leqembi).
Key Findings at 36 Months
- The treated group showed ~ 0.95 points less decline on the CDR-SB (Clinical Dementia Rating – Sum of Boxes) scale compared to a predefined natural history cohort.
- Among patients with low baseline tau accumulation (“no tau / low tau” subgroup), 59 % demonstrated improvement or no decline vs baseline on CDR-SB.
- No new safety signals were reported. Incidence of amyloid-related imaging abnormalities (ARIA) declined after the first 6–12 months and remained stable.
- A 30 % reduction in relative risk of progressing to the next disease stage (versus natural history comparator) was reported.
Context & Interpretation
These 36-month data add to the growing evidence that continuous administration of lecanemab can lead to a more durable slowing of cognitive decline in early Alzheimer’s disease, beyond the 18-month core trial period.
However, there are important caveats and considerations:
- The comparisons are made against a predefined natural history cohort (rather than an internal placebo arm at 36 months), introducing potential bias or population mismatches.
- Subgroup findings (e.g. “no tau / low tau”) may not generalise to all patients with early Alzheimer’s.
- Although no new ARIA signals emerged, ARIA remains an established risk in anti-amyloid therapy; close monitoring is necessary—especially early on.
- The press release does not deeply discuss dropouts, missing data, or other statistical adjustments needed in long-term studies. Additional peer-reviewed publications would be needed to validate robustness.
Implications & Next Steps
If these results hold in further validation, they strengthen the case for long-term continuous use of Leqembi in early Alzheimer’s disease, especially in patients at early pathological stages (low tau). From a regulatory and commercial perspective, they help support ongoing filings, label expansions, and real-world adoption.
Eisai and Biogen are also investigating a subcutaneous (SC) maintenance dosing option of lecanemab — transitioning from intravenous to a 360 mg weekly SC autoinjector — and have reported that this may maintain comparable efficacy and safety to IV dosing.
Balanced Perspective: Strengths & Uncertainties
Strengths:
- Longer follow-up enhances confidence in durability of effect.
- Safety profile over extended exposure seems acceptable, with ARIA incidence declining after early period.
- Subgroup analyses provide insight into which patients may derive most benefit.
Uncertainties & risks:
- No internal placebo arm beyond ~18 months, so external comparators must be interpreted with caution.
- Missing data, attrition bias, and patient selection may impact observed effect sizes.
- Biomarker and tau progression data remain relatively limited at this horizon.
- Regulatory, reimbursement, and access challenges (cost, imaging requirements, monitoring) may limit broad adoption.
