Model-Informed Drug Development Approach Supporting Approval of Adalimumab (HUMIRA) in Adolescent Patients with Hidradenitis Suppurativa: a Regulatory Perspective.

On October 16, 2018, FDA expanded the adalimumab dosing regimen to adolescent hidradenitis suppurativa (HS) patients 12 years and older, weighing at least 30 kg without new clinical data. This approval was mainly supported by the model-informed drug development approach. Population pharmacokinetic simulations suggest body weight-tiered dosing regimens in adolescent patients will achieve similar exposure to adult patients across all weight range. Adalimumab has a well-established, 16-year long-term safety profile in various diseases in adult and pediatric populations. Current data of adalimumab in the pediatric population demonstrate no exposure-response relationship for adverse events. The effectiveness in adolescent patients was extrapolated from two adequate and well-controlled phase 3 studies in adult patients, assuming similar positive exposure-efficacy relationships in adults and adolescents. This article provides the insight of the application of MIDD on the adalimumab approval in adolescent HS patients and its implication on drug development and regulatory decision especially for pediatrics or rare diseases.