SAT-187 Efficacy And Safety Of Somapacitan In Non-GHD Adolescents With Short Stature: 26-week Results From The REAL9 Phase 3 Study

Abstract Disclosure: A.K. Maniatis: Ascendis, Novo Nordisk, OPKO, Pfizer, Inc. M. Højby: Novo Nordisk. M.Y. Jalaludin: Novo Nordisk. A.A. Jorge: Novo Nordisk, Merck, Pfizer, Inc., Biomarin. J. Mori: Novo Nordisk, Pfizer, Inc. K. Soltysik: Novo Nordisk. R. Stawerska: Ascendis, OPKO, Novo Nordisk, Pfizer, Inc., Sandoz. A. Linglart: Novo Nordisk, Pfizer, Inc.. Short stature in children can be caused by a variety of factors. In the case of short children born small for gestational age (SGA), girls with Turner syndrome (TS), children with Noonan syndrome (NS) or idiopathic short stature (ISS), growth hormone (GH) secretion assessed by stimulation tests is usually normal, although GH sensitivity may be decreased and IGF-I impaired. Daily GH injections can improve longitudinal growth for such children, but treatment can be burdensome for patients/caregivers. Somapacitan is a long-acting reversible albumin-binding GH derivative in development for once-weekly subcutaneous (s.c.) administration in these indications. REAL9 (NCT05723835) is an interventional, multi-national, open-labelled, and uncontrolled phase 3 study, comprising a 26-week main phase followed by a first 130-week extension phase and a second 91-week extension phase to evaluate long-term safety and efficacy of somapacitan administered s.c. once-weekly (0.24 mg/kg/week) in older children and adolescents (aged >10 or >11 years for girls and boys, respectively) born SGA, or with TS, NS, or ISS. This study supports the pivotal phase 3 REAL8 study (NCT05330325) in treatment-naïve prepubertal children born SGA, or with TS, NS, or ISS. In total, the study enrolled 12 participants born SGA (4 GH-treatment-naïve), 11 girls with TS (4 GH-treatment-naïve), 13 participants with NS (6 GH-treatment-naïve), and 11 participants with ISS (2 GH-treatment-naïve). All participants completed 26-weeks of treatment with somapacitan. Across all indications, growth-related endpoints (height velocity, change in height standard deviation score (SDS), and change in height velocity SDS) showed an expected increase in treatment-naïve participants as well as maintenance in participants switching from daily GH to somapacitan. PK/PD model-derived weekly IGF-I average SDS values were in the same range as that determined for younger children in the REAL8 study. Somapacitan was well tolerated and had a safety profile similar to the well-known safety profile of daily GH. Adverse events (AEs) were either mild or moderate in severity across all indications, withno dose reductions required. One AE of injection site bruising was reported for one participant with NS as well as one participant with TS. No participants reported injection site pain with somapacitan. In conclusion, 26-weeks of treatment with somapacitan showed a safety and tolerability profile in older children and adolescents across all four indications (SGA, TS, NS, and ISS) similar to younger children. In addition, somapacitan effectively improved longitudinal growth in treatment-naïve participants and maintained growth in participants previously treated with daily GH. Presentation: Saturday, July 12, 2025