Model-informed drug development to support nemolizumab clinical development in adults and adolescents with moderate to severe atopic dermatitis

Authors

Floris Fauchet, Certara USA, Inc., Radnor, PA, USA.
Anna Largajolli, Certara USA, Inc., Radnor, PA, USA.
Petra M. Jauslin, Certara USA, Inc., Radnor, PA, USA.
Emilie Schindler, Roche Pharma Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, Basel, Switzerland.
Mourad Hamimed, Certara USA, Inc., Radnor, PA, USA.
Wannee Kantasiripitak, Certara USA, Inc., Radnor, PA, USA.
Antonio Gonçalves, Certara USA, Inc., Radnor, PA, USA.
Eline Van Maanen, Certara USA, Inc., Radnor, PA, USA.
Khaled Benkali, Certara USA, Inc., Radnor, PA, USA.
Tomohisa Saito, Chugai Pharmaceutical Co., Ltd, Tokyo, Japan.
Jonathan I. Silverberg, Department of Dermatology, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
Andreas Wollenberg, Department of Dermatology and Allergology, Ludwig-Maximilians-Universität, Munich, Germany.
Michael Graeber, Galderma R&D, Fort Worth, Texas, USA.
Liliana Ulianov, Galderma R&D, Lausanne, Switzerland.
Christophe Piketty, Galderma R&D, Zug, Switzerland.
Luca Loprete, Galderma R&D, Zug, Switzerland.
Vincent Duval, Certara USA, Inc., Radnor, PA, USA.
Nathalie Wagner, Galderma R&D, Fort Worth, Texas, USA.

Document Type

Journal Article

Publication Date

1-15-2026

Journal

British journal of clinical pharmacology

DOI

10.1002/bcp.70435

Keywords

NONMEM; atopic dermatitis; dermatology; model‐informed drug development; nemolizumab; pharmacokinetics; pharmacokinetic‐pharmacodynamic

Abstract

AIMS: Population pharmacokinetic (popPK) and pharmacokinetic-pharmacodynamic (PK/PD) models were developed to support clinical development of nemolizumab, a humanized monoclonal antibody targeting the IL-31 receptor α, in adolescents and adults with moderate-to-severe atopic dermatitis (AD). METHODS: Starting from previous analyses, data from phase 2 to phase 3 studies in AD and prurigo nodularis were integrated into popPK model development. In initial PK/PD model development, a turnover model was used for Eczema Area and Severity Index (EASI) and Peak Pruritus Numerical Rating Scale (PP NRS) endpoints, while a continuous-time Markov model was used for Investigator's Global Assessment (IGA) scores. A model-informed drug development (MIDD) approach based on popPK and PK/PD modelling and simulations was applied to support dose selection in patients with AD. RESULTS: Nemolizumab exposures decreased with increasing bodyweight. The popPK simulation predicted different median Ctroughs according to bodyweight <90 kg or ≥90 kg: 2.51 vs. 1.71 μg/mL, respectively. However, PK/PD simulations showed that the proportion of responders for EASI, PP NRS and IGA endpoints was similar in both groups: 37.5%, 55.6% and 31.6% vs. 35.1%, 53.4% and 26.3% for bodyweight <90 kg or ≥90 kg, respectively. Reduced response of IGA to nemolizumab treatment was identified for male subjects (23.4% vs. 34.0%) and severe baseline score (19.3% vs. 32.3%) with consistent trends between bodyweight group. CONCLUSIONS: The overall MIDD approach supported the nemolizumab program by confirming the recommended dosing regimen of 30 mg every four weeks with a 60 mg loading dose in all patients with AD.

APA Citation

Fauchet, Floris; Largajolli, Anna; Jauslin, Petra M.; Schindler, Emilie; Hamimed, Mourad; Kantasiripitak, Wannee; Gonçalves, Antonio; Van Maanen, Eline; Benkali, Khaled; Saito, Tomohisa; Silverberg, Jonathan I.; Wollenberg, Andreas; Graeber, Michael; Ulianov, Liliana; Piketty, Christophe; Loprete, Luca; Duval, Vincent; and Wagner, Nathalie, "Model-informed drug development to support nemolizumab clinical development in adults and adolescents with moderate to severe atopic dermatitis" (2026). GW Authored Works. Paper 8564.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/8564

Department

Dermatology