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.
Fauchet et al. (2026) studied this question.