Phase 3 Trial Shows Lonapegsomatropin Is Superior to Somatropin in Treatment-Naïve Children with Growth Hormone Deficiency

The investigational long-acting, once-weekly prodrug lonapegsomatropin (TransCon hGH) may be more beneficial to treatment-naïve pediatric patients with growth hormone deficiency (GHD) than daily somatropin of equivalent weekly dose, according to a paper recently published in The Journal of Clinical Endocrinology & Metabolism.

Researchers led by Aimee D. Shu, MD, of Ascendis Pharma (who funded the trial), point out that children with GHD have been treated with daily injections of somatropin (recombinant human GH) since 1987, and although the drug is safe and does help children achieve normal height, results don’t always match expectations. Children and their caregivers don’t particularly like daily injections, leading to noncompliance rates ranging from 5% to 82%. “In 2015, the Growth Hormone Research Society recognized the need for a long-acting growth hormone (LAGH) and agreed that by decreasing injection frequency and offering different pharmacokinetic properties, a LAGH would potentially improve adherence and outcomes,” the authors write.

The Phase 3 heiGHt trial enrolled 161 treatment-naïve, prepubertal patients with GHD, and randomized the children 2:1 to receive lonapegsomatropin 0.24 mg hGH/kg/week or an equivalent weekly dose of somatropin delivered daily. The researchers found that after 52 weeks, patients taking lonapegsomatropin had a an ANCOVA-adjusted least squares (LS) mean (SE) annualized height velocity (AHV) of 11.2 cm compared to 10.3 cm for the children taking somatropin. The observed AHV range was 5.9 to 18.0 cm/year and 4.7 to 16.3 cm/year for lonapegsomatropin and daily somatropin, respectively.

“The Phase 3 heiGHt trial of weekly lonapegsomatropin in treatment-naïve pediatric patients with GHD demonstrated superior AHV and statistically greater change in height SDS from baseline compared to a commercially available daily somatropin of equivalent weekly dose, with a similar safety and tolerability profile,” the authors write. “Importantly, the bone age to chronological age ratio advanced similarly in both groups, suggesting that the increased rate of longitudinal growth did not occur at the expense of accelerated skeletal maturation.”

The researchers go on to conclude that fundamental challenge of developing a LAGH is to create a more convenient dosing regimen while retaining the excellent safety, efficacy, and tolerability of daily somatropin. “Building on the concept of releasing unmodified somatropin to maintain physiologic distribution, weekly lonapegsomatropin is the first LAGH with data demonstrating superior efficacy compared to a daily somatropin, while maintaining similar bone age advancement, AE profile, and immunogenicity,” they write. “Lonapegsomatropin may represent an important therapeutic option for children with GHD.”