Subcutaneous Lecanemab
(2025)Objective
To establish the bioavailability and bioequivalence of subcutaneous lecanemab formulations (vial and autoinjector) compared to intravenous lecanemab in healthy adults, supporting development of a more convenient and safer dosing option for anti-amyloid therapy.
Study Summary
• Autoinjector produced ~25% higher Cmax and ~20% higher AUC than vial/syringe; formal bioequivalence NOT demonstrated (upper 90% CI exceeded 125% reference)
• Despite failing strict bioequivalence, exposure-response modeling predicted similar amyloid plaque lowering and efficacy across IV, SC vial, and autoinjector
• Injection site reactions in 20.7% of SC subjects vs infusion-related reactions in 33.3% of IV subjects (mild/moderate)
• Half-life ~7 days in both SC and IV groups
Intervention
Subcutaneous lecanemab (700 mg or 720 mg fixed dose, via vial/syringe or autoinjector) compared to intravenous lecanemab 10 mg/kg.
Inclusion Criteria
Healthy adult participants.
Study Design
Arms: Study 1 (bioavailability): SC lecanemab 700 mg (n=29) vs IV lecanemab 10 mg/kg (n=30). Study 2 (bioequivalence): SC lecanemab 720 mg via vial/syringe (n=80) vs SC lecanemab 720 mg via autoinjector (n=80).
Patients per Arm: Study 1: SC n=29, IV n=30. Study 2: Vial/syringe n=80, Autoinjector n=80.
Outcome
• Autoinjector Cmax 67.4 µg/mL vs vial/syringe 53.7 µg/mL (~25% higher)
• Autoinjector AUC(0-inf) 20,900 vs vial/syringe 17,500 µg·h/mL (~20% higher)
• Bioequivalence between autoinjector and vial/syringe NOT met (upper 90% CI > 125%)
• Half-life ~7 days in both groups
• Injection site reactions: 6/29 (20.7%) with SC; infusion-related reactions: 10/30 (33.3%) with IV
• Exposure-response modeling predicted comparable amyloid plaque lowering across all three administration routes
Bottom Line
Subcutaneous lecanemab (vial or autoinjector) achieves approximately 50% absolute bioavailability versus IV but produces comparable steady-state exposure with a more favorable injection-related adverse event profile. Despite the autoinjector failing strict bioequivalence versus vial/syringe (~25% higher Cmax, ~20% higher AUC), exposure-response modeling predicts comparable amyloid plaque lowering and clinical efficacy across all three administration routes, supporting continued development of SC lecanemab as a more convenient alternative to IV infusion.
Major Points
- Two phase 1 single-dose studies in healthy adults: bioavailability (n=60, SC vs IV) and bioequivalence (n=160, SC vial vs autoinjector)
- Absolute bioavailability of SC lecanemab (vial) was 49.7% (90% CI: 43.5-56.8) relative to IV
- Autoinjector administration produced ~25% higher Cmax (67.4 vs 53.7 µg/mL) and ~20% higher AUC (AUC0-inf 20,900 vs 17,500 µg·h/mL) than vial/syringe
- Strict bioequivalence between autoinjector and vial/syringe was NOT demonstrated — upper 90% CI of geometric mean ratio exceeded the 125% reference bound
- Half-life of lecanemab was approximately 7 days in both SC and IV groups
- Injection site reactions (mild/moderate) occurred in 20.7% of SC subjects vs infusion-related reactions (grade 1-2) in 33.3% of IV subjects
- Exposure-response modeling predicted comparable amyloid plaque lowering and efficacy for IV, SC vial, and SC autoinjector
- SC injection of lecanemab via vial or autoinjector yielded comparable average steady-state concentrations to IV administration
Study Design
- Study Type
- Two single-dose phase 1 clinical trials in healthy adults
- Randomization
- Yes
- Sample Size
- 220
- Follow-up
- 50 days of serum lecanemab measurement
Primary Outcome
Definition: Pharmacokinetic comparability — absolute bioavailability of SC vs IV lecanemab (Study 1) and bioequivalence of SC vial/syringe vs autoinjector (Study 2)
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| Study 1 IV 10 mg/kg; Study 2 vial/syringe Cmax 53.7 µg/mL, AUC(0-t) 17,100 µg·h/mL, AUC(0-inf) 17,500 µg·h/mL | Study 1 SC 700 mg (absolute bioavailability 49.7%); Study 2 autoinjector Cmax 67.4 µg/mL, AUC(0-t) 20,600 µg·h/mL, AUC(0-inf) 20,900 µg·h/mL | - (Absolute bioavailability 90% CI: 43.5-56.8%) |
Limitations & Criticisms
- Healthy-adult phase 1 design — does not directly assess clinical efficacy or ARIA risk in the target Alzheimer's population
- Strict bioequivalence between autoinjector and vial/syringe was not met; reliance on exposure-response modeling to bridge to efficacy
- Single-dose PK only — no steady-state data from repeated dosing in this report
- Conference abstract — limited detail on demographics, statistical methods, and ARIA monitoring
Citation
Penner N, Rawal S, Aluri J, et al. Development of Subcutaneous Lecanemab: Establishing the Comparability of Subcutaneous and Intravenous Lecanemab Formulations. Alzheimer's Dement. 2025;21(Suppl. 5):e104694.