This pivotal phase 3 trial led to the recent approval of lonapegsomatropin for growth hormone deficiency.
A recent study detailed the findings of a pivotal phase 3 trial that evaluated the efficacy, safety, and tolerability of weekly lonapegsomatropin vs daily somatropin for growth hormone deficiency (GHD).
Findings were recently published in The Journal of Clinical Endocrinology and Metabolism.
Lonapegsomatropin is a long-acting version of somatropin and was recently approved by the FDA to treat GHD. It is administered once weekly, while somatropin, or recombinant human growth hormone (GH), is administered daily. The authors said daily injections have been found to be burdensome, leading to nonadherence rates of 5% to 82% in real-world settings. GH is necessary for bone growth and is needed for organ development, cardiovascular function, cognition, and metabolism, they said.
Lonapegsomatropin is a prodrug that consists of 3 parts: somatropin, an inert methyoxy polyethelene glycol carrier, and a proprietary linker. The heiGHt trial that led to its approval was a randomized, open-label, active-controlled, 52-week trial at 73 sites in 15 countries.
Diagnosis of GHD was defined as peak GH ≤10 ng/mL confirmed via 2 GH stimulation tests. Participants also had to have a height SD score (SDS) ≤ −2.0, insulin-like growth factor 1 (IGF-1) SDS ≤ −1.0, body mass index within ±2.0 SD of the mean, and bone age ≥6 months behind chronological age, determined by a blinded radiologist.
Investigators enrolled and dosed 161 treatment-naive, prepubertal patients with GHD; they were randomized 2:1 to receive lonapegsomatropin 0.24 mg hGH/kg/week or an equivalent weekly dose of somatropin delivered daily.
After the screening visit, patients attended 6 visits at weeks 1 (baseline), 5, 13, 26, 39, and 52 for height and weight measurements, blood sampling for laboratory parameters, pharmacokinetic, IGF-1 and IGF binding protein 3 measurements, immunogenicity testing, and adverse event (AE) monitoring. Bone age was read by a blinded central bone age reader.
The primary end point was annualized height velocity (AHV) at week 52. Secondary efficacy end points included change from baseline in height SDS.
Of the 161 patients, 159 completed the trial. Mean adherence rates were 99.6% for lonapegsomatropin and 98.6% for somatropin.
The least squares (LS) mean (SE) AHV at 52 weeks was 11.2 (0.2) cm/year for lonapegsomatropin vs 10.3 (0.3) cm/year for daily somatropin (P = .009). Lonapegsomatropin showed both noninferiority and superiority over daily somatropin, the authors said.
The LS mean (SE) height SDS increased from baseline to week 52 by 1.10 (0.04) vs 0.96 (0.05) in the weekly lonapegsomatropin vs daily somatropin groups (P = .01).
Bone age/chronological age ratio, AEs, tolerability, and immunogenicity were similar between groups. The results indicate that "the increased rate of longitudinal growth did not occur at the expense of accelerated skeletal maturation," the authors wrote.
There were no serious AEs (SAEs) related to the study drug, and no AE led to treatment discontinuation or death. Rates of SAEs and AEs were similar between groups, the researchers reported.
The trial met its primary objective of noninferiority in AHV and further showed superiority of lonapegsomatropin compared with daily somatropin, with similar safety, in treatment-naive children with GHD
Thornton PS, Maniatis AK, Aghajanova E, et al. Weekly lonapegsomatropin in treatment-naïve children with growth hormone deficiency: the phase 3 heiGHt trial. J Clin Endocrinol Metab. Published online July 17, 2021. doi:10.1210/clinem/dgab529