Once-weekly Somapacitan in Children with Noonan Syndrome: Randomised Controlled Phase 3 Trial

Abstract Objective Daily growth hormone (GH) injections are indicated for the treatment of short stature in children with Noonan syndrome, which presents a treatment burden for the child and their parents/caregivers. Somapacitan is a long-acting, reversible albumin-binding GH, developed for once-weekly administration. The objective of this study is to evaluate efficacy, safety and tolerability of somapacitan versus daily GH in children living with Noonan syndrome. Design REAL8 (NCT05330325) is a multi-national, multi-centre, randomised, open-labelled, active comparator, phase 3 basket study including four non-GH deficiency indications comprising a 52-week main phase and 104-week extension. Here, we present 52-week results from the REAL8Noonan syndrome sub-study. Methods Seventy-seven GH-treatment-naïve, prepubertal boys (aged 2.5 to 11 years) and girls (aged 2.5 to 10 years) with Noonan syndrome were randomized 2:1 to somapacitan 0.24 mg/kg/week or daily GH 0.050 mg/kg/day, administered subcutaneously. Results The primary endpoint, estimated mean annualized height velocity at week 52, was 10.4 cm/year for somapacitan versus 9.2 cm/year for daily GH (estimated treatment difference ETD: 1.2, 95% CI 0.32; 2.03), confirming non-inferiority and demonstrating superiority of somapacitan compared to daily GH (p0.01). The estimated change from baseline to week 52 in height standard deviation score was 1.07 and 0.75 for somapacitan and daily GH, respectively (ETD: 0.32, 95% CI 0.16; 0.48). Somapacitan was well tolerated and had a similar safety profile to daily GH. Conclusion Once-weekly somapacitan was confirmed as non-inferior and demonstrated superiority to daily GH in HV after 52 weeks of treatment in treatment-naïve children living with Noonan syndrome. Similar safety profiles and tolerability were observed for both groups.