Population Pharmacokinetic and Pharmacodynamic Modeling for the Prediction of the Extended Amlitelimab Phase 3 Dosing Regimen in Atopic Dermatitis

ABSTRACT Amlitelimab is a fully human, nondepleting, anti‐OX40 ligand monoclonal antibody being investigated for the treatment of moderate‐to‐severe atopic dermatitis (AD) in adults and adolescents. Population pharmacokinetic (PopPK) and pharmacokinetic/pharmacodynamic‐Eczema Area and Severity Index (PopPK/PD‐EASI) models were used to inform dosing regimen selection for amlitelimab phase 3 trials. The PopPK model was developed using phase 1 (healthy volunteers) and phase 2 (participants with AD) trial data, including individual exposure variables from the STREAM‐AD phase 2b trial following subcutaneous amlitelimab doses ranging from 62.5 to 250 mg given every 4 weeks (Q4W). The PopPK model was used to compute exposures for an extended dosing regimen of 250 mg Q12W (with 500 mg loading dose +LD). The PopPK/PD‐EASI model was developed from phase 2 trials to predict treatment responses (EASI values) with selected dosing scenarios. Finally, the dose for individuals with lower body weight (i.e., < 40 kg) was determined. Utilizing the PopPK model, the amlitelimab 250 mg Q12W + LD computed exposures were between the exposures of 62.5 mg Q4W and 250 mg Q4W + LD efficacious doses in the STREAM‐AD trial. Using the PopPK/PD‐EASI model, the simulated efficacy for dosing scenarios of 250 mg Q12W + LD regimen from initiation or 250 mg Q4W + LD for 24 weeks followed by Q12W to Week 60 was similar to continuous 250 mg Q4W. Simulations identified that a twofold dose reduction would allow participants < 40 kg to achieve amlitelimab exposures within the range observed in participants ≥ 40 kg on 250 mg Q4W or Q12W. These results support evaluation of a Q12W dosing regimen for adults and adolescents in phase 3 trials.