OR10-06 Somatrogon Growth Hormone in the Treatment of Pediatric Growth Hormone Deficiency: Results of the Pivotal Pediatric Phase 3 Clinical Trial

Background: Somatrogon (hGH-CTP) is a long acting recombinant human growth hormone (rhGH; somatropin) in development for once weekly treatment of children with growth hormone deficiency (GHD). Somatrogon contains the amino acid sequence of hGH and three copies of the carboxy-terminal peptide (CTP) derived from human chorionic gonadotropin. A 12 month phase 2 trial of once weekly Somatrogon vs daily Genotropin in children with GHD demonstrated that 0.66 mg/kg/wk of Somatrogon had a similar benefit - risk profile as 0.24 mg/kg/wk of Genotropin. The open label extension of this phase 2 study has generated an additional 5 years of longitudinal efficacy and safety data with this dose. This report summarizes top line results from a pivotal phase 3 global trial (ClinicalTrials.gov: NCT02968004) designed to investigate the non-inferiority of once weekly Somatrogon hGH-CTP compared to daily hGH after 12 months in treatment-naive prepubertal children with GHD. Methods: The Phase 3 trial enrolled 224 subjects who were randomized in a 1:1 ratio to receive either once weekly Somatrogon hGH-CTP (0.66 mg/kg) or once daily Genotropin (0.24 mg/kg/wk) for 12 months. Randomization was stratified by geographic region, peak GH level and age. The primary endpoint of the study was height velocity (HV) at month 12; secondary endpoints included HV at month 6, change in height SDS at month 6 and 12, IGF-1 and IGF-I SDS, immunogenicity, and safety. Results: At baseline, the mean (SD) age and height SDS of the somatrogon (N=109, 75.2% male) and Genotropin (N=115, 68.7% male) groups were 7.83 (2.66) and -2.94 (1.29) and 7.61 (2.37) and -2.78 (1.27), respectively. One subject in each group discontinued during the 12 month study, and 95% of the completers continued into an open-label extension study. At month 12, mean HV was 10.12 cm/yr in the Somatrogon group and 9.78 cm/yr in the Genotropin group, with the treatment difference of 0.33 cm/year favoring Somatrogon. The lower bound of the two-sided 95% confidence interval of the treatment difference was -0.39, which was higher than the pre-established non-inferiority margin and demonstrated non-inferiority of once weekly somatrogon vs daily Genotropin therapy. Height velocity at month 6 (10.60 cm/yr vs 10.04 cm/yr), change in height SDS at months 6 (0.54 vs 0.48) and 12 (0.92 vs 0.87) were likewise numerically higher in the Somatrogon-treated cohort. The majority of adverse events were mild to moderate in severity (somatrogon: 78.9%, Genotropin: 79.1%) and, overall, weekly somatrogon was generally well-tolerated and comparable to daily Genotropin. Conclusion: Top-line results from the pivotal phase 3 trial demonstrate that Somatrogon (hGH-CTP) given once weekly by sc injection is non-inferior to Genotropin (hGH) given once daily and that once weekly somatrogon administration was generally well-tolerated in patients with pGHD.