Safety and Efficacy of Lonapegsomatropin in Children With Growth Hormone Deficiency: enliGHten Trial 2-Year Results

Abstract

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 lonapegsomatropin in children with growth hormone deficiency.

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 United States switched to the TransCon hGH Auto-Injector when available. Endpoints were long-term safety, annualized height velocity, pharmacodynamics [insulin-like growth factor-1 SD score (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 second year of therapy without excess advancement of bone age.

Trial registration: ClinicalTrials.gov NCT03344458.

Keywords: TransCon hGH; growth hormone; growth hormone deficiency; growth hormone replacement therapy; lonapegsomatropin; long-acting growth hormone.

© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society.

Figures

Figure 1.

Sustained improvement in height SD score (SDS) for heiGHt subjects. Changes in height SDS over 104 weeks in treatment-naïve subjects who enrolled in the heiGHt trial and continued into the enliGHten trial. Subjects who were treated with daily somatropin in heiGHt (blue bars) switched to weekly lonapegsomatropin in enliGHten (orange bars). Subjects who were on weekly lonapegsomatropin in heiGHt continued weekly lonapegsomatropin in enliGHten (green bars). *Based on n = 159 at heiGHt trial baseline. +ΔHeight SDS value is the least squares means from the analysis of covariance model.

Figure 2.

Sustained improvement in height SD score (SDS) for fliGHt subjects. Height SDS over 78 weeks in subjects who had been previously treated with daily somatropin before enrolling in the fliGHt trial (weekly lonapegsomatropin, light purple background) and then continuing in the enliGHten trial (weekly lonapegsomatropin, light orange background). *Based on n= 146 at fliGHt baseline.

Figure 3.

Average insulin-like growth factor-1 (IGF-1) SD score (SDS) over 104 weeks for heiGHt subjects. Average IGF-1 SDS over 104 weeks for patients who were treated with lonapegsomatropin (green line, triangles) or daily somatropin (blue line, circles) in the heiGHt trial and were treated with lonapegsomatropin in the enliGHten trial (orange lines, triangles or circles).

Figure 4.

Body mass index (BMI) SD score (SDS) across all trials. BMI SDS for subjects from the fliGHt trial who were treated with lonapegsomatropin (purple line, stars) and continued lonapegsomatropin in the enliGHten trial (orange line, stars), subjects from the heiGHt trial who were treated with daily somatropin (blue line, circles) and were treated with lonapegsomatropin in the enliGHten trial (orange line, circles), and subjects from the heiGHt trial who were treated with lonapegsomatropin (green line, triangles) and were treated with lonapegsomatropin in the enlighten trial (orange line, triangles).