Model-based somapacitan dosing and IGF-I response in children born SGA or with ISS, Noonan or Turner Syndromes

Introduction The weekly IGF-I profile for children and adolescents treated with long-acting growth hormone differs from that of daily growth hormone (GH). This study provides guidance on the use of once-weekly somapacitan and IGF-I monitoring in prepubertal short children and adolescents born small for gestational age (SGA) or with idiopathic short stature (ISS), Noonan syndrome (NS), or Turner syndrome (TS). Methods Modeling, including population pharmacokinetic/pharmacodynamic (PK/PD) modeling, were utilized, analysing IGF-I data from four clinical studies, including two phase 3 trials (REAL8: NCT05330325; REAL9: NCT05723835) involving children and adolescents born SGA (N=80), ISS (N=69), NS (N=62), and TS (N=79), along with additional data from phase 2 (REAL5: NCT03878446, N=59) and phase 1 trials (NCT01973244, N=24). Results Relationships between somapacitan dose, exposure, baseline IGF-I SD score (SDS), and height velocity (HV) were established in children born SGA, with similar responses anticipated for those with ISS, NS, or TS. A linear model enabled the estimation of average weekly IGF-I exposure from a single sample collected during the somapacitan dosing interval. IGF-I SDS simulations support flexible dosing changes while maintaining a minimum of 4 days between doses. Conclusions Somapacitan 0.24 mg/kg/week produced similar IGF-I SDS changes and height velocity increases as daily GH in prepubertal short children and adolescents born SGA or with ISS, NS, or TS. The results support that the guidance already established for GHD regarding somapacitan initiation, dosing flexibility, and IGF-I monitoring remain appropriate for prepubertal short children and adolescents born SGA or with ISS, NS, or TS.