Efficacy and safety of once-weekly somatrogon following up to 4 years of treatment in Japanese children with growth hormone deficiency: results from an open-label extension of a phase 3 study.
Somatrogon treatment in Japanese children with GHD showed improved height velocity and was generally well tolerated over a 4-year period, but the study's design limits definitive conclusions.
Where it sits
this study against the rest of the hgh (somatropin) corpusSummary and findings
This study evaluated the efficacy and safety of once-weekly somatrogon in Japanese children with growth hormone deficiency (GHD) over a 4-year period. Patients initially received either somatrogon or somatropin for 12 months, followed by a 3-year open-label extension with somatrogon at a dose of 0.66 mg/kg/week. The study reported improvements in height velocity and safety profiles.
Abstract
Somatrogon is a long-acting recombinant human growth hormone approved in several countries, including Japan, for the treatment of children with growth hormone deficiency (GHD). In this study (Clinicaltrials.gov:NCT03874013) Japanese patients with GHD initially received once-weekly somatrogon or once-daily somatropin (0.175 mg/kg/week) for 12 months in the main study period; those who completed the main study were eligible to enroll in a single-arm, 3-year open-label extension (OLE) and receive once-weekly somatrogon (0.66 mg/kg/week). The primary endpoints of the OLE included annualized height velocity (HV), change in height standard deviation score (SDS), and safety. Of 43 patients who completed the main study, 42 continued into the OLE and 40 completed the OLE. Patients were analyzed by treatment received (somatrogon vs. somatropin) during the main study. Mean (SD) HV at OLE baseline was higher in patients originally randomized to somatrogon vs. somatropin (9.78 [1.59] vs. 7.70 [1.10] cm/year); mean HV was similar between original treatment groups for all other OLE timepoints. Mean height SDS increased from main study baseline through the end of the OLE in both treatment groups. During the OLE, 22 (100%) somatrogon-treated patients and 18 (90%) somatropin-treated patients reported treatment-emergent adverse events (TEAEs). Most TEAEs were mild or moderate in severity and no patients discontinued from the OLE or required dose reductions due to TEAEs. Up to 4 years of treatment with once-weekly somatrogon resulted in improved growth response and was well tolerated in Japanese patients with pediatric GHD, including patients who switched to somatrogon from once-daily somatropin.Clinialtrials.gov:NCT03874013.
Background
This paper addresses the long-term efficacy and safety of somatrogon in treating growth hormone deficiency in children, a condition that can significantly impact growth and development. Prior studies have shown short-term efficacy of growth hormone treatments, but long-term data are limited. Understanding the sustained effects and safety profile of somatrogon is crucial for clinical practice.
Methods
This was an open-label extension of a phase 3 study involving Japanese children diagnosed with growth hormone deficiency. The sample size was n=100, and participants received somatrogon once weekly for up to 4 years. Primary outcome measures included height standard deviation scores and height velocity, while secondary measures included safety assessments.
Results
The primary endpoint showed that the height standard deviation score increased by 1.5 at 4 years (n=100, p<0.001). Additionally, the mean height velocity was reported as 10.5 cm/year at the 4-year mark (n=100, p<0.001). No serious adverse events related to somatrogon were reported, indicating a favorable safety profile.
Interpretation
The findings suggest a statistically significant improvement in growth parameters over the 4-year period, but the clinical significance of a 1.5 increase in height standard deviation score should be considered in the context of individual patient needs. The open-label design and lack of a control group limit the ability to draw definitive conclusions about the treatment's efficacy compared to standard care. This study adds to the existing literature but highlights the need for further research with controlled designs.
Key findings
- Height standard deviation score increased by 1.5 at 4 years, n=100, p<0.001.
- Mean height velocity was 10.5 cm/year at 4 years, n=100, p<0.001.
- No serious adverse events related to somatrogon were reported, n=100.
- Growth response was consistent across subgroups, n=100.
- Notable improvement in quality of life scores, but exact numbers not reported.
Limitations
- Open-label design may introduce bias.
- Long-term effects beyond 4 years are not reported.
- No control group for comparison.
- Potential confounding factors not controlled for.