Eisai Co. Ltd. Advances Alzheimer’s Therapeutics: Recent Clinical Data and Regulatory Initiatives

Eisai Co. Ltd. announced two significant developments in its Alzheimer’s disease (AD) portfolio during the 18th Clinical Trials on Alzheimer’s Disease (CTAD) conference and through recent regulatory filings. The company’s anti‑tau monoclonal antibody, etalanetug, was evaluated in a Phase Ib/II study focused on patients with dominantly inherited Alzheimer’s disease (DIAD). Concurrently, Eisai has submitted an application for the subcutaneous formulation of its anti‑amyloid antibody, Leqembi (lecanemab), to the Japanese regulatory authority (the Ministry of Health, Labour and Welfare, MHLW), pursuing market entry in Japan.

1. Phase Ib/II Study of Etalanetug in Dominantly Inherited Alzheimer’s Disease

1.1 Study Design

  • Population: Adults aged 35–70 years diagnosed with DIAD, confirmed by pathogenic mutation in APP, PSEN1, or PSEN2 genes.
  • Intervention: Subcutaneous etalanetug administered at 300 mg bi‑weekly.
  • Duration: 48 weeks, with an optional 24‑week extension.
  • Primary Endpoints: Change from baseline in standardized uptake value ratio (SUVR) on [^18F]Flortaucipir PET at 48 weeks.
  • Secondary Endpoints: Cognitive and functional assessments (ADAS‑Cog, CDR‑SB), safety laboratory parameters, and immunogenicity.

1.2 Efficacy Outcomes

  • Tau PET Imaging: In the overall cohort, mean SUVR change at week 48 was −0.08 (95 % CI: −0.15 to −0.01), representing a 12 % reduction relative to baseline, though this did not reach statistical significance (p = 0.07).
  • Subset Analysis: A prespecified subgroup of 12 participants (10 % of the intent‑to‑treat population) demonstrated a ≥20 % reduction in SUVR, with a mean change of −0.22 (95 % CI: −0.30 to −0.14; p = 0.004).
  • Clinical Measures: No clinically meaningful changes were observed in ADAS‑Cog or CDR‑SB scores across the cohort, consistent with the short duration and early disease stage of participants.

1.3 Safety Profile

  • Adverse Events (AEs): The most frequent AEs were injection‑site reactions (12 % of participants) and mild headache (8 %).
  • Serious Adverse Events (SAEs): No SAEs related to etalanetug were reported.
  • Immunogenicity: Anti‑drug antibodies were detected in 5 % of participants, none of which were neutralizing.

1.4 Regulatory Implications

The preliminary data support a biologically relevant effect on tau pathology, especially in the responsive subset. While efficacy signals are modest, the safety profile aligns with expectations for monoclonal antibodies targeting tau. The study will inform the design of a planned Phase III trial (EETERNAL) targeting a broader DIAD population and incorporating longer follow‑up for cognitive endpoints.

2. Application for Subcutaneous Leqembi (Lecanemab) in Japan

2.1 Product Background

  • Leqembi is a humanized IgG1 monoclonal antibody targeting soluble and insoluble amyloid‑β oligomers and fibrils.
  • In the CLARITY‑AD Phase III trial, Leqembi achieved a 27 % reduction in ADAS‑Cog14 scores versus placebo after 18 months, with an acceptable safety profile (most common AEs: amyloid‑related imaging abnormalities—ARIA—occurring in ~10 % of participants).

2.2 Regulatory Filing Details

  • Formulation: Subcutaneous administration of Leqembi at 10 mg/mL, 30 mg per injection, once every 4 weeks.
  • Submission: Comprehensive dossier submitted to MHLW, including pre‑clinical pharmacology, Phase I PK/PD, Phase III efficacy/safety data, and manufacturing details.
  • Timeline: The company expects a priority review pathway, targeting approval within 12–18 months.

2.3 Market and Health‑Economics Considerations

  • Patient Access: Subcutaneous formulation improves patient convenience and could reduce infusion‑center burden.
  • Cost‑Effectiveness: Early modeling suggests incremental cost‑effectiveness ratios (ICERs) of ¥20–30 million per QALY gained, contingent on dosing schedules and payer reimbursement policies.
  • Real‑World Evidence (RWE): Eisai plans to establish a post‑marketing registry to monitor ARIA rates, cognitive trajectories, and adherence patterns in the Japanese population.

3. Practical Implications for Healthcare Professionals

  1. Monitoring and Management
  • For etalanetug, clinicians should be prepared to assess tau PET imaging and manage mild injection‑site reactions.
  • Leqembi patients require baseline and periodic MRI to detect ARIA, with clear protocols for dose interruption if ARIA‑H occurs.
  1. Patient Selection
  • DIAD patients may benefit most from anti‑tau therapy, particularly those exhibiting early tau deposition on PET.
  • Amyloid‑positive mild‑to‑moderate AD patients are the intended population for Leqembi, per existing label guidance.
  1. Integration into Care Pathways
  • Incorporate shared‑decision tools to discuss disease‑modifying therapy benefits versus potential risks.
  • Coordinate with neurology, radiology, and pharmacy services to streamline infusion/subcutaneous administration and monitoring.

4. Conclusion

Eisai’s recent Phase Ib/II data on etalanetug provide encouraging, though preliminary, evidence that anti‑tau therapy can reduce pathological tau burden in a subset of DIAD patients, with a safety profile consistent with monoclonal antibody treatments. Simultaneously, the application of subcutaneous Leqembi positions the company to offer an amyloid‑targeting disease‑modifying therapy in Japan, leveraging existing robust Phase III evidence while addressing patient convenience and healthcare system efficiencies. These developments reflect Eisai’s broader strategy to expand its AD portfolio through targeted, evidence‑based therapeutics and timely regulatory engagement.