Comprehensive Assessment of Pharmacokinetics, Pharmacodynamics, and Tolerability of Ligelizumab in Healthy Volunteers and Patients with Chronic Spontaneous Urticaria to Optimize Its Subcutaneous Delivery System

Ligelizumab is a highly potent, humanized IgG1, anti-IgE monoclonal antibody. To explore its optimal subcutaneous delivery, the pharmacokinetics (PK), pharmacodynamics (PD), and tolerability of ligelizumab from two Phase 1 studies in healthy volunteers (HVs) and four Phase 2 and 3 studies in patient...

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Bibliographic Details
Published in:Pharmaceutics 2023-09, Vol.15 (9), p.2266
Main Authors: Ji, Yan, Calonder, Claudio, Kirsilä, Tiina, Burciu, Alis, Tisu, Matjaz, Joubert, Yolandi, Laurent, Nathalie, Hua, Eva, Patekar, Manmath, Drollmann, Anton, Woessner, Ralph
Format: Article
Language:English
Subjects:
Abdomen
Analysis
anti-IgE
Drug dosages
formulation
Health care industry
Immunoglobulin E
Immunoglobulin G
ligelizumab
Manufacturing
Medical research
Medicine, Experimental
Monoclonal antibodies
Patient compliance
Pharmacodynamics
Pharmacokinetics
prefilled syringe
subcutaneous delivery
Urticaria
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Summary:Ligelizumab is a highly potent, humanized IgG1, anti-IgE monoclonal antibody. To explore its optimal subcutaneous delivery, the pharmacokinetics (PK), pharmacodynamics (PD), and tolerability of ligelizumab from two Phase 1 studies in healthy volunteers (HVs) and four Phase 2 and 3 studies in patients with chronic spontaneous urticaria (CSU) were assessed. Using different injection volumes or durations of a liquid-in-vial (LIVI) formulation or different formulations (LIVI vs. prefilled syringe (PFS)), single-dose ligelizumab showed comparable PK exposure in HVs. Steady-state exposure of ligelizumab was also comparable between LIVI and PFS following multiple dosing in CSU patients. The total IgE level (a PD marker) and tolerability were similar between the two formulations in both HVs and patients. Furthermore, the PK, total IgE, and tolerability were comparable for PFS administered either by patients or healthcare providers (HCPs). Collective evidence demonstrated that the injection duration or volume, formulation, or administrator had no apparent impact on the PK, PD, and tolerability of ligelizumab, supporting no clinically relevant difference between LIVI and PFS, and that PFS can be administered by patients or HCPs. This report provides a comprehensive assessment based on data of multiple clinical endpoints from both HVs and patients to inform formulation development and commercial use of a monoclonal antibody.
ISSN:1999-4923
1999-4923
DOI:10.3390/pharmaceutics15092266