ESPE Abstracts

Objectives: Somatrogon is a long-acting recombinant human growth hormone (GH) approved by the EMA as a once weekly treatment for children with GH deficiency (GHD). The peak stimulated GH cut-off value for diagnostic criteria for GHD varies according to country-specific guidelines. The objective of this subgroup analysis of the pivotal phase 3 somatrogon study was to evaluate the primary and secondary efficacy endpoints for subjects with a peak GH value <6.7 ng/ml.

Methods: This phase 3 study enrolled 224 subjects, randomized 1:1 to receive either once-weekly somatrogon (0.66mg/kg/week) or once-daily Genotropin (0.24mg/kg/week) for 12 months. Randomization was stratified by geographic region, peak GH level, and age. The study’s primary endpoint 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, IGF-1 SDS, and bone maturation. This subgroup analysis focused on 135 subjects with a peak GH value <6.7 ng/ml (67 subjects received somatrogon and 68 received Genotropin).

Results: In this subgroup, the least squares (LS) mean HV at month 12 was 10.11 cm/year and 9.77 cm/year in somatrogon- and Genotropin-treated subjects, respectively, with the treatment difference of 0.34 cm/year favoring somatrogon. This was similar to the overall study population (Peak GH value <10 ng/ml), whose LS mean HV at month 12 was 10.10 cm/year and 9.78 cm/year for somatrogon- and Genotropin-treated subjects, respectively, with a treatment difference of 0.33 favoring somatrogon. The efficacy of once-weekly somatrogon was statistically demonstrated to be non-inferior to once-daily Genotropin in the overall study population. In this subgroup, mean changes in height SDS at months 6 (0.57 vs 0.50) and 12 (0.96 vs 0.91) were numerically higher in somatrogon-treated subjects. Stratification by age (3 to 7 years, >7 years), gender, and region showed most values for HV and change in height SDS at months 6 and 12 were higher for the somatrogon group compared with the Genotropin group. The increase in IGF-1 SDS from baseline to month 12 was higher in the somatrogon group (+2.84) vs the Genotropin group (+1.06). Mean bone maturation observed at 12 months was similar between both groups (both 0.69).

Conclusions: The findings from this analysis of subjects with a peak GH value <6.7 ng/ml are consistent with those from the overall study population, in which non-inferiority of once-weekly somatrogon to once-daily Genotropin was statistically demonstrated. Clinicaltrials.gov:NCT02968004