Drug Development

Area of Science:

• Pharmacology and Drug Development
• Clinical Trials and Therapeutics
• Neuroscience and Neurology

Background:

• Developing subcutaneous lecanemab aims to enhance patient convenience and safety.
• Early development focuses on establishing bioavailability and bioequivalence of subcutaneous versus intravenous formulations.

Purpose of the Study:

• To assess the bioavailability and pharmacokinetic profile of subcutaneous lecanemab.
• To determine the bioequivalence of lecanemab administered via vial versus autoinjector.
• To predict the efficacy of subcutaneous lecanemab formulations through exposure-response modeling.

Main Methods:

• Two Phase 1 clinical trials were conducted in healthy adults.
• Study 1: Randomized assessment of absolute bioavailability and pharmacokinetics of subcutaneous vs. intravenous lecanemab.
• Study 2: Randomized assessment of bioequivalence between subcutaneous lecanemab vial and autoinjector.

Main Results:

• Subcutaneous lecanemab showed mild injection site reactions; intravenous had infusion-related reactions.
• Absolute bioavailability of subcutaneous lecanemab was 49.7%.
• Bioequivalence was not demonstrated between vial and autoinjector, though exposure-response models predicted similar efficacy for all formulations.

Conclusions:

• Subcutaneous lecanemab administration (vial or autoinjector) achieved comparable average steady-state concentrations to intravenous administration.
• Exposure-response modeling suggests similar amyloid plaque lowering and efficacy across administration routes.
• Subcutaneous lecanemab holds potential for improved patient-centric administration.