Establishing PK Equivalence Between Adalimumab and ABP 501 in the Presence of Antidrug Antibodies Using Population PK Modeling

PurposeABP 501 (European Union, adalimumab; United States, adalimumab-atto) is a biosimilar to the adalimumab reference product (RP). A model was developed characterizing population pharmacokinetic (PK) variables of ABP 501 and adalimumab RP to include the impact of antidrug antibodies (ADAs).MethodsData were retrospectively analyzed from a single-dose, parallel-group bioequivalence study in healthy adults who received a single 40-mg SC injection of ABP 501 or adalimumab RP. Modeling was performed by using NONMEM 7.2. The impact of ADAs on PK similarity was assessed from population model-based AUC0–∞ values using ANCOVA.FindingsLinear compartment models with various clearance pathways were compared with a one-compartment distribution, first-order subcutaneous absorption model. The final model, a one-compartment model with first-order subcutaneous absorption and linear clearance from the central compartment with an additional time-dependent linear clearance for ADA-positive subjects, described ABP 501 and adalimumab RP population PK variables. Model-derived estimates confirmed PK similarity for ABP 501 and adalimumab RP despite the impact of ADAs.ImplicationsA traditional approach for evaluating bioequivalence based on noncompartmental analysis may be inappropriate for drugs with a high incidence of ADAs because accounting for the effect of ADAs on noncompartmental analysis parameters is challenging. Use of a population PK model to discern the effect of ADAs on drug PK variables allows for assessment of PK similarity accounting for the presence or absence of ADAs.