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Subcutaneous Lecanemab: Expanding Options for Maintenance Therapy in Early Alzheimer's Disease

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Introduction

The treatment landscape for early Alzheimer's disease (AD) continues to evolve with the advent of disease-modifying therapies targeting amyloid-beta. Lecanemab (LEQEMBI), a humanized IgG1 monoclonal antibody, is approved for patients with mild cognitive impairment (MCI) or mild dementia due to AD. It selectively binds to soluble Abeta protofibrils and insoluble fibrils, accelerating plaque clearance and slowing downstream tau pathology (Hayato et al., 2022).

While intravenous (IV) lecanemab every two weeks remains the established initiation regimen, the recent approval of a subcutaneous (SC) autoinjector formulation (LEQEMBI IQLIK) for weekly maintenance dosing represents a pivotal shift toward patient-centered, long-term therapy (Eisai Inc., 2025b).

Pharmacokinetics and Bioequivalence

The SC development program sought to establish bioequivalence with IV therapy, ensuring comparable efficacy while potentially improving safety and convenience.

  • Bioavailability: Early SC vial formulations demonstrated absolute bioavailability of approximately 49.7% in healthy volunteers and 62.7% in AD patients (Hayato et al., 2022).
  • Exposure Equivalence: A 500 mg weekly SC autoinjector achieved drug exposure (AUC) equivalent to the 10 mg/kg IV dose administered biweekly (Willis et al., 2023).
  • Maintenance Dosing: The FDA-approved 360 mg weekly SC regimen provides exposure sufficient to sustain biomarker and clinical benefits comparable to IV dosing (Irizarry et al., 2025).

Importantly, SC administration yields a substantially lower maximum concentration (Cmax), which is strongly associated with the risk of Amyloid-Related Imaging Abnormalities with edema (ARIA-E).

Efficacy: Clinical and Biomarker Outcomes

Evidence from the Clarity AD open-label extension (OLE) and PK/PD modeling supports SC maintenance as clinically equivalent to IV therapy.

  • Amyloid Clearance: At 12 months, SC dosing achieved 18% greater amyloid reduction compared with IV (Hayato et al., 2022).
  • Biomarker Maintenance: Weekly 360 mg SC dosing maintained plasma Abeta42/40 ratios, pTau181, and GFAP levels consistent with inhibition of AD pathology and neuroinflammation (Eisai Inc., 2025c).
  • Clinical Outcomes: Long-term follow-up through 48 months demonstrates continued benefit versus natural history, with SC dosing projected to sustain CDR-SB outcomes similar to IV regimens (Tahami Monfared et al., 2025).

Safety Profile

The SC formulation offers meaningful safety advantages, particularly regarding ARIA and systemic reactions.

  • ARIA Risk Reduction: Modeling predicts markedly lower ARIA-E incidence with SC versus IV, especially in APOE ε4 carriers (Willis et al., 2023). In the Clarity AD OLE, no ARIA-E events occurred among 49 patients on 360 mg SC maintenance over 6 months (Irizarry et al., 2025).
  • Systemic Infusion Reactions: Occurred in less than 1% of SC-treated patients compared to 26% with IV infusions (Eisai Inc., 2025c).
  • Local Reactions: Injection-site erythema, swelling, or tenderness occurred in approximately 11% of patients, generally mild and not leading to discontinuation (Eisai Inc., 2025c).
  • Immunogenicity: Rates of anti-drug antibodies remain low across both routes (2-3%) (Willis et al., 2023).

Administration and Clinical Integration

The LEQEMBI IQLIK autoinjector is a two-step, approximately 15-second device that can be administered by patients or caregivers. Human factors studies confirmed greater than 95% usability across patients, caregivers, and healthcare professionals, even in cognitively impaired populations (Irizarry et al., 2025).

Regimen:

  1. Initiation: 18 months of 10 mg/kg IV infusions every two weeks.
  2. Maintenance: Transition to 360 mg SC weekly via autoinjector, or 10 mg/kg IV every four weeks.

System-Level Implications:

  • Reduced demand for infusion center resources.
  • Expanded access for patients with transportation or mobility limitations.
  • Societal cost savings projected at $72,000-$80,000 per patient over four years compared to IV therapy (Tahami Monfared et al., 2025).

Clinical Considerations for Providers

  • ApoE E4 Genotyping remains essential prior to initiation due to differential ARIA risk.
  • MRI Monitoring is still required, particularly during IV initiation where ARIA risk is highest.
  • Patient Education on autoinjector technique, storage (refrigeration), and management of local reactions is vital for successful implementation.

Conclusion

The subcutaneous formulation of lecanemab represents a paradigm shift in Alzheimer's care, delivering comparable efficacy to IV therapy with improved safety and convenience. For providers, the ability to transition patients to at-home, weekly injections after the initiation phase not only enhances adherence but also alleviates strain on healthcare infrastructure. With lower systemic risks and meaningful reductions in caregiver burden, SC lecanemab offers a practical, sustainable pathway for long-term disease modification in early AD.

References

Access the full article: alz-journals.onlinelibrary.wiley.com
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