Lonapegsomatropin Provides Height Improvements in Later Tanner Stages without Increase in Dose

Lonapegsomatropin, a once-weekly prodrug of somatropin, can help children in Tanner Stages 3-5 maintain consistent height standard deviation scores (SDS) without an increase in the mean dose, according to a study presented at ENDO 2023. Ascendis Pharma is marketing the drug as TransCon hGH.

Researchers led by Paul Hofman, MD, FRACP, of the Liggins Institute and the University of Auckland in New Zealand, point out that many pediatric endocrinologists advocate increasing  growth hormone doses in later puberty to mimic normal adolescent physiology and maximize growth outcomes. The researchers analyzed outcomes from three phase 3 trials investigating the safety and efficacy pf lonapegsomatropin — the heiGHt (treatment-naïve trial), the fliGHt (switch trial), and the enliGHten (open-label extension trial). “The enliGHten open-label extension trial of once-weekly lonapegsomatropin provided the opportunity to evaluate dosing, efficacy, and safety outcomes in a group of children that includes more advanced Tanner Stages,” the authors write.

For this study, the researchers examined the association between Tanner Stage and IGF-1 SDS measurements, lonapegsomatropin dose, and height SDS using mixed repeated models with the Tanner Stage as the time-varying covariate. They found that later Tanner Stages (3-5) were correlated with higher average IGF-1 SDS, compared to lower Tanner Stages (1-2). Adolescents in Tanner Stages 4 and 5 received the lowest mean dose. “Among patients with dose reduction, a decrease of lonapegsomatropin of 0.02 mg hGH/kg corresponded to a consistent drop in average IGF-1 SDS across all Tanner Stages,” the authors write. “Participants across all subgroups experienced continued growth as expected over time.”

“This analysis showed that it was possible to maintain consistent height SDS improvements in children and adolescents in Tanner Stages 3-5 without an increase in the mean lonapegsomatropin dose,” the authors conclude. “Lonapegsomatropin dose reductions resulted in predictable linear IGF-1 decreases across Tanner Stages.”