Context For children with growth hormone deficiency (GHD), treatment burden with daily somatropin injections (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/wk 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 standard deviation 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 non-inferiority 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 non-inferiority in AHV and further showed superiority of lonapegsomatropin compared to daily somatropin, with similar safety, in treatment-naïve children with GHD.

The study showed a 0.05% prevalence of thyroid hemiagenesis in asymptomatic schoolchildren population from iodine-sufficient area of Northern Poland.

Introduction: The objective of this study was to analyse the effects of the first three years of treatment with recombinant human insulinlike growth factor 1 (rhIGF-1) in patients from the Polish population. Material and methods: Twenty-seven children (22 boys and five girls) aged 2.8 to 16.0 years old were qualified for treatment with rhIGF-1 (mecasermin) in different treatment centres, according to Polish criteria: body height below-3.0 SD and IGF-1 concentration below percentile 2.5 with normal growth hormone (GH) levels. Mecasermin initial dose was 40 μg/kg bw twice a day and was subsequently increased to an average of 100 μg/kg bw twice a day. Body height, height velocity, weight, body mass index (BMI), and adverse events were measured. Results: Mecasermin treatment resulted in a statistically significant increase in body height (1.45 ± 1.06 SD; p < 0.01) and height velocity in comparison with pre-treatment values. The biggest change in height velocity happened during the first year and diminished during subsequent years. Body weight and BMI also increased significantly after treatment (1.16 ± 0.76 SD and 0.86 ± 0.75 SD, respectively; p < 0.01). Eight patients reported adverse events. These were mild and temporary and did not require treatment modification except in two patients. Conclusions: Treatment with rhIGF-1 was effective and safe in Polish patients with primary IGF-1 deficiency. It had a clear beneficial effect on the height of the patients and significantly accelerated the height velocity, particularly in the first year of treatment.

Background: The most effective growth hormone (GH) treatment regimen for increasing height in short children born small for gestational age (SGA) has not been well defined. Methods: Short SGA children (n = 151, age 3–8 years, height less than –2.5 standard deviation scores) were randomised to receive low-dose GH for 2 years (0.033/0.033 mg/kg/day, n = 51), high-dose GH for 1 year and then no treatment for 1 year (0.100/0 mg/kg/day, n = 51) or were untreated for 1 year then received mid-dose GH for 1 year (0/0.067 mg/kg/day, n = 47). Height, bone age and adverse events were determined at check-ups every 3 months. Results: The mean ± SD additional height gain with GH after 1 year, relative to untreated controls, was higher with discontinuous high-dose than with continuous low-dose GH (6.5 ± 0.2 vs. 3.3 ± 0.2 cm). After 2 years, the additional height gain was similar between high- and low-dose GH groups (between-group treatment difference = 0.2, 95% CI = –0.8 to 1.2 cm, p = 0.702). Patients treated exclusively in the last year had a similar height gain to those in the other treatment groups (p = 0.604). Conclusions: In short SGA children, continuous low-dose and discontinuous high-dose GH regimens were associated with similar height gain. Treatment with mid-dose GH for 1 year also led to a similar improvement in growth.

Purpose The objectives of the ongoing, Phase 3, open-label extension trial enliGHten are to assess the long-term safety and efficacy of weekly administered long-acting growth hormone (LAGH) lonapegsomatropin in children with growth hormone deficiency (GHD). Methods Eligible subjects completing a prior Phase 3 lonapegsomatropin parent trial (heiGHt or fliGHt) were invited to participate. All subjects were treated with lonapegsomatropin. Subjects in the US switched to the TransCon hGH Auto-Injector when available.​ Endpoints were long-term safety, annualized height velocity (AHV), pharmacodynamics (insulin-like growth factor-1 standard deviation score [IGF-1 SDS] values), and patient- and caregiver-reported assessments of convenience and tolerability. Results Lonapegsomatropin treatment during enliGHten was associated with continued improvements in height SDS through Week 104 in treatment-naïve subjects from the heiGHt trial (−2.89 to −1.37 for- the lonapegsomatropin group; −3.0 to −1.52 for the daily somatropin group). Height SDS also continued to improve among switch subjects from the fliGHt trial (−1.42 at fliGHt baseline to −0.69 at Week 78). After 104 weeks, the average bone age/chronological age ratio for each treatment group was 0.8 (0.1), showing only minimal advancement of bone age relative to chronological age with continued lonapegsomatropin treatment among heiGHt subjects. Fewer local tolerability reactions were reported with the TransCon hGH Auto-Injector compared with syringe/needle. Conclusions Treatment with lonapegsomatropin continued to be safe and well-tolerated, with no new safety signals identified. Children treated with once-weekly lonapegsomatropin showed continued improvement of height SDS through the 2nd year of therapy without excess advancement of bone age.