Somatropin (rbe) 10mg/2ml solution for injection cartridges

Long-acting growth hormone (LAGH) has the potential to improve adherence and outcomes over daily somatropin in growth hormone deficiency (GHD). Whereas daily somatropin products are molecularly identical, LAGHs are molecularly distinct; additional moieties or mechanisms that prolong LAGH action confer unique pharmacodynamic/pharmacokinetic properties that could affect efficacy and safety. Only one LAGH available in the United States and Europe (lonapegsomatropin) delivers unmodified somatropin. With no head-to-head clinical trials of LAGHs available, this systematic literature review and network meta-analysis were conducted to compare the relative efficacy and safety of LAGHs in pediatric GHD. Five trials were eligible for inclusion in a Bayesian network meta-analysis; 3 contributed to the base case network, including 3 LAGHs (lonapegsomatropin, somapacitan, and somatrogon) and daily somatropin. Treatment with lonapegsomatropin was associated with statistically significantly higher annualized height velocity and change from baseline in height SD score (SDS) at week 52 compared to daily somatropin and somapacitan; no other significant differences in these outcomes were found. The change from baseline in average insulin-like growth factor-1 (IGF-1) SDS at week 52 was significantly higher for somatrogon vs all comparators and for lonapegsomatropin vs daily somatropin and somapacitan; average IGF-1 SDS was within normal range in all trials. No significant differences were seen in progression in bone age-to-chronological age ratio or serious adverse events (SAEs). Sensitivity analyses were consistent with the base case. In this network meta-analysis, lonapegsomatropin was the only LAGH associated with better growth outcomes. No significant differences were detected regarding SAEs; other safety outcomes could not be analyzed.

Abstract licence: CC BY

IntroductionLonapegsomatropin, a prodrug of somatropin, is approved for once-weekly treatment of paediatric growth hormone deficiency (GHD) in the USA and Europe. Here, we report the first trial to assess the efficacy and safety of weekly lonapegsomatropin compared to daily somatropin in treatment-naive Chinese children with GHD.MethodsThe briGHt trial was a randomized, open-label, active-controlled, 52-week, phase 3 trial (NCT04326374; CTR20200399) conducted at 17 sites across China. Treatment-naive, prepubertal children with GHD were enrolled and randomized 2:1 to either lonapegsomatropin 0.24 mg hGH/kg/week or equivalent weekly dose of daily somatropin 0.034 mg/kg/day. The primary endpoint was annualized height velocity (AHV) at week 52. Secondary endpoints included change in height standard deviation score (ΔHT SDS) from baseline, insulin-like growth factor 1, and safety.ResultsA total of 153 participants received treatment. Least squares (LS) mean ± standard error (±SE) of AHV at week 52 was 10.66 ± 0.22 cm/year for weekly lonapegsomatropin and 9.75 ± 0.26 cm/year for daily somatropin; weekly lonapegsomatropin demonstrated non-inferiority and superiority over daily somatropin, with a difference of 0.91 ± 0.28 cm/year (95% confidence interval: 0.37-1.45; p = 0.0010). LS mean (±SE) of ΔHT SDS was 1.01 ± 0.04 for weekly lonapegsomatropin and 0.83 ± 0.05 for daily somatropin at week 52, favouring lonapegsomatropin from week 13 (p ConclusionsWeekly lonapegsomatropin demonstrated non-inferiority and superiority in efficacy compared to daily somatropin among treatment-naive Chinese children with GHD. The treatment groups showed comparable safety and tolerability profiles.

Abstract licence: CC BY-NC