Lonapegsomatropin (TransCon hGH) is an investigational once-weekly prodrug of somatropin for the treatment of GHD. Previous trials in treatment-naïve (52-week heiGHt Trial) and treatment-experienced children (26-week fliGHt Trial) have reported the efficacy and safety of lonapegsomatropin. Subjects were eligible to enter the open-label extension enliGHten Trial, which continues to evaluate weekly lonapegsomatropin in pediatric GHD. In heiGHt, treatment-naïve subjects received lonapegsomatropin (Group A; vial/syringe) or daily somatropin (Group B; pen device). In fliGHt, treatment-experienced subjects switched to lonapegsomatropin from daily somatropin (Group C; vial/syringe). Lonapegsomatropin was administered at a starting dose of 0.24 mg hGH/kg/wk. Upon entry into enliGHten, all subjects received lonapegsomatropin (vial/syringe), and switched to TransCon hGH Auto-Injector pending regional availability. A total of 298 (of 303 eligible) subjects continued into enliGHten (A: n = 103; B: n = 55; C: n = 140). The mean dose remained approximately 0.24 mg hGH/kg/wk for Group A/B at Week 104 and was 0.20 mg hGH/kg/wk for Group C at Week 78. Subjects starting heiGHt on daily somatropin who switched to lonapegsomatropin continued to approach their average parental height, with height standard deviation score (SDS) improving from -3.0 at baseline to -1.52 at Week 104. Subjects from the fliGHt Trial also continued to approach their average parental height, with height SDS improving from −1.42 at fliGHt baseline to −0.69 at Week 78. Observed Mean annualized height velocity (AHV) at Week 78 was 8.4 cm/year. heiGHt subjects starting lonapegsomatropin continued to approach their average parental height, with height SDS improving from -2.89 at baseline to -1.37 at Week 104. As of the data cut (01 June 2020), 5 subjects have met or exceeded their target height and 11 subjects have grown to within 2 cm of their target height. Mean (SD) average IGF-1 SDS remained stable and generally within the expected range for all groups (Week 104, A: 0.95 [1.22], B: 1.04 [1.25]; Week 78, C: 1.81 [1.08]). Across all phase 3 trials, lonapegsomatropin produced a dose linear IGF-1 response. With lonapegsomatropin treatment, the adverse event (AE) profile remained consistent with what was observed in the parent trials, with no new safety signals, comparable tolerability, and a mean body mass index (BMI) SDS approaching zero. Across the broad population of the phase 3 program, subjects treated with lonapegsomatropin for up to 2 years continued to approach their average parental height, with a safety profile comparable to daily somatropin, including a similar AE profile, tolerability, and stable BMI.
22 Sep 2021 - 26 Sep 2021