Weekly Lonapegsomatropin in Treatment–Naïve Children With Growth Hormone Deficiency: The Phase 3 heiGHt Trial

Abstract

Abstract Context For children with growth hormone deficiency (GHD), treatment burden with daily somatropin injections [human growth hormone (hGH)] is high, which may lead to poor adherence and suboptimal overall treatment outcomes. Lonapegsomatropin (TransCon hGH) is an investigational long-acting, once-weekly prodrug for the treatment of GHD. Objective The objective of this study was to evaluate the efficacy and safety of once-weekly lonapegsomatropin vs daily somatropin. Design The heiGHt trial was a randomized, open-label, active-controlled, 52-week Phase 3 trial (NCT02781727). Setting This trial took place at 73 sites across 15 countries. Patients This trial enrolled and dosed 161 treatment-naïve, prepubertal patients with GHD. Interventions Patients were randomized 2:1 to receive lonapegsomatropin 0.24 mg hGH/kg/week or an equivalent weekly dose of somatropin delivered daily. Main Outcome Measure The primary end point was annualized height velocity (AHV) at week 52. Secondary efficacy end points included change from baseline in height SD scores (SDS). Results Least squares (LS) mean (SE) AHV at 52 weeks was 11.2 (0.2) cm/year for lonapegsomatropin vs 10.3 (0.3) cm/year for daily somatropin (P = 0.009), with lonapegsomatropin demonstrating both noninferiority and superiority over daily somatropin. LS mean (SE) height SDS increased from baseline to week 52 by 1.10 (0.04) vs 0.96 (0.05) in the weekly lonapegsomatropin vs daily somatropin groups (P = 0.01). Bone age/chronological age ratio, adverse events, tolerability, and immunogenicity were similar between groups. Conclusions The trial met its primary objective of noninferiority in AHV and further showed superiority of lonapegsomatropin compared to daily somatropin, with similar safety, in treatment-naïve children with GHD.