Lecanemab (BAN2401) Infusion Reactions and Immunogenicity: Results from Randomized Phase 2 Study and an Open‐Label Extension (OLE).

Abstract

AbstractBackgroundTreatment with 10 mg/kg lecanemab (BAN2401), a humanized IgG1 monoclonal antibody that preferentially targets soluble aggregated Aβ species, has been shown to reduce amyloid PET standard uptake value ratio (SUVr) and slow clinical decline in an 18‐month, phase 2 proof‐of‐concept study (Study 201 Core) in early Alzheimer’s disease with an OLE. The present analysis aimed to review infusion related reactions from Study 201 and the results of immunogenicity assessments from the completed lecanemab clinical trial.MethodsInfusion related reactions were summarized by treatment group using descriptive statistics. All adverse events were coded using MedDRA version 24.0 and graded based on CTCAE guidelines.Analysis of anti‐drug antibodies (ADA) and its impact on pharmacokinetics, pharmacodynamics, efficacy, and safety during Study 201 were undertaken. All ADA and NAb assays were developed and validated in accordance with FDA guidance and industry best practice and were performed using a tiered approach.ResultsIn Study 201 Core, 854 treated subjects (lecanemab:609; placebo:245) were randomized across 6 treatment groups. In the OLE phase a total of 180 subjects were treated with lecanemab 10 mg/kg biweekly (LEC10BW). Infusion‐related reactions were the most common adverse event associated with LEC10BW treatment, with 19.9% (32/161) of subjects compared to 3.3% (8/245) of placebo subjects. All events were mild/moderate in severity, most occurred with the first infusion, resulted in a low rate of discontinuations (LEC10BW:2.5%; placebo:0.8%). Over 70% of patients who initially experienced infusion‐related reactions had no further reactions with preventative medications. Infusion reaction data from the OLE were consistent with the Core study. The incidences of ADA for LEC10BW in the Core and OLE were 40.9% and 11.1% (Core placebo‐treated subjects), respectively; titers were very low (most ≤125). Detailed analysis of lecanemab ADA demonstrated no meaningful impact of ADA on pharmacokinetics, pharmacodynamics, efficacy, and safety.ConclusionsIn the lecanemab Study 201 Core and OLE, infusion‐related reactions were the most common adverse event, however were readily manageable with preventative medication, were of low severity, and resulted in minimal discontinuations. Lecanemab is a low‐risk molecule for immunogenicity based on ADA profile and minimal impact of ADA on pharmacokinetics, pharmacodynamics, efficacy, and safety.