Efficacy and Safety of Lonapegsomatropin in Children With Turner Syndrome: 52-Week Results From the New InsiGHTS Trial.
Lonapegsomatropin showed comparable efficacy to daily somatropin in improving height outcomes in children with Turner syndrome over 52 weeks, but the clinical significance of the differences remains uncertain.
Where it sits
this study against the rest of the hgh (somatropin) corpusSummary and findings
This study evaluated the efficacy and safety of lonapegsomatropin in 49 prepubertal children with Turner syndrome over 52 weeks. The primary endpoint was annualized height velocity (AHV) at week 26, with secondary endpoints including AHV at week 52 and changes in height standard deviation score (SDS). Results indicated comparable efficacy between lonapegsomatropin and daily somatropin.
Abstract
<h4>Context</h4>Treatment with growth hormone is effective in improving height outcomes in children with Turner syndrome. However, poor adherence-often influenced by daily injection burden-may compromise treatment outcomes. Lonapegsomatropin is a prodrug, administered once weekly, that provides sustained release of somatropin.<h4>Objective</h4>To evaluate the efficacy and safety of lonapegsomatropin in children with Turner syndrome.<h4>Design</h4>New InsiGHTS is a phase 2 dose-ranging trial (ClinicalTrials.gov: NCT05690386).<h4>Setting</h4>This trial was conducted across 19 centers in the United States.<h4>Participants</h4>This trial enrolled and dosed 49 prepubertal children with Turner syndrome.<h4>Interventions</h4>Randomization was 1:1:1:1 to receive once-weekly lonapegsomatropin (0.24, 0.30, or 0.36 mg hGH/kg/week) or daily somatropin (0.35 mg/kg/week).<h4>Main outcome measure</h4>The primary efficacy endpoint was annualized height velocity (AHV) at week 26. Secondary efficacy endpoints included AHV at week 52 and change from baseline in height standard deviation score (SDS) at weeks 26 and 52.<h4>Results</h4>At week 26, AHV was comparable between lonapegsomatropin starting dose cohorts (range: 9.23 to 10.36 cm/year) and the somatropin cohort (10.86 cm/year). At week 52, AHV was comparable between pooled lonapegsomatropin cohorts (9.05 cm/year) and the somatropin cohort (9.04 cm/year), with mean gains in height SDS of 0.60 and 0.67, respectively. Lonapegsomatropin was well tolerated with a safety profile similar to somatropin.<h4>Conclusions</h4>Across evaluated doses, lonapegsomatropin treatment demonstrated comparable efficacy, safety, and tolerability to somatropin after 1 year, supporting development of lonapegsomatropin as a once-weekly treatment option for short stature in children with Turner syndrome.
Background
This paper addresses the efficacy of lonapegsomatropin, a prodrug of somatropin, in improving height outcomes for children with Turner syndrome. Previous treatments with daily growth hormone have shown effectiveness but may suffer from adherence issues due to injection frequency. This study is significant as it explores a once-weekly administration that could enhance adherence and treatment outcomes.
Methods
The study was a phase 2 dose-ranging trial involving 49 prepubertal children with Turner syndrome. Participants were randomized in a 1:1:1:1 ratio to receive either lonapegsomatropin at doses of 0.24, 0.30, or 0.36 mg hGH/kg/week or daily somatropin at 0.35 mg/kg/week. The primary outcome measure was annualized height velocity (AHV) assessed at week 26, with secondary measures at week 52.
Results
At week 26, AHV was comparable across lonapegsomatropin cohorts (9.23 to 10.36 cm/year) and the somatropin cohort (10.86 cm/year). At week 52, pooled lonapegsomatropin cohorts achieved an AHV of 9.05 cm/year, while the somatropin cohort had an AHV of 9.04 cm/year. Mean gains in height SDS were 0.60 for lonapegsomatropin and 0.67 for somatropin at week 52.
Interpretation
The findings suggest that lonapegsomatropin has comparable efficacy to daily somatropin, although the effect sizes in height gain may not be clinically significant given the small differences in SDS. The study's small sample size and short duration limit the ability to draw robust conclusions about long-term efficacy and safety. Practitioners should consider these factors when evaluating treatment options for Turner syndrome.
Key findings
- At week 26, AHV was 9.23 to 10.36 cm/year for lonapegsomatropin cohorts and 10.86 cm/year for the somatropin cohort.
- At week 52, AHV was 9.05 cm/year for pooled lonapegsomatropin cohorts and 9.04 cm/year for the somatropin cohort.
- Mean gains in height SDS at week 52 were 0.60 for lonapegsomatropin and 0.67 for somatropin.
Limitations
- small sample size of 49 participants
- short follow-up of 52 weeks
- comparative efficacy may not be clinically significant
- multi-center study may introduce variability