Efficacy, Safety and Pharmacokinetics of Semaglutide 1.7 mg for Obesity Treatment in Adolescents: A Model-Informed Drug Development Approach.

AIMS: Treatment options for adolescents with obesity are limited, and some may benefit from lower maintenance doses of semaglutide. This study used model-informed drug development (MIDD) to evaluate whether a 1.7-mg maintenance dose provides comparable exposure, tolerability and BMI effects in adolescents versus adults and versus the 2.4-mg dose. MATERIALS AND METHODS: Simulation analyses combined pharmacokinetic, BMI and safety data from the adolescent STEP TEENS Phase 3 study (N = 201) and the adult semaglutide STEP studies (Phases 2-3; ~3100 participants). Data across doses (0.25-2.4 mg) were used to model concentration-time profiles, extrapolate percent change in BMI for 1.7 mg, estimate proportions achieving ≥ 5%, ≥ 10% and ≥ 15% BMI reductions and predict gastrointestinal adverse event (AE) incidence as a function of exposure. RESULTS: Modelled semaglutide concentrations over 68 weeks were similar between adolescents and adults; body weight was the main covariate influencing exposure. For adolescents, the 1.7-mg dose showed comparable efficacy to 2.4 mg (mean BMI change: -15.2% vs. -17.4%) and was significantly greater than placebo (p < 0.01). Predicted proportions achieving prespecified BMI reduction thresholds and gastrointestinal AE profiles were similar across populations and doses. CONCLUSIONS: PK/PD and safety modelling indicated 1.7 mg semaglutide provides comparable exposure, tolerability and meaningful BMI reduction in adolescents versus adults and versus 2.4 mg. These results supported approval of 1.7 mg for adolescents ≥ 12 years in the November 2024 Wegovy label, obviating a dedicated adolescent 1.7-mg placebo trial.