Open-Label 9-Year Follow-Up Extension Phase 2 Study of Once-Weekly Somatrogon in Children With Growth Hormone Deficiency

CONTEXT: : Growth hormone deficiency (GHD) can lead to significant growth and developmental issues, necessitating long-term treatment. Once-weekly somatrogon is a long-acting recombinant human growth hormone analogue, approved for treatment of children with GHD. OBJECTIVE: : Assess the long-term safety and efficacy of somatrogon in children with GHD. DESIGN: : Open-label extension (OLE) study following an initial 12-month open-label phase 2 study. SETTING: : Conducted at 14 centers across Hungary, Bulgaria, Belarus, Ukraine, Russia, Greece, and the US. PATIENTS OR OTHER PARTICIPANTS: : Fifty-three children with GHD (67.9% male, mean age 6.0±2.1 years) completed the phase 2 study and 48 entered the OLE. INTERVENTION(S): : Participants received once-weekly somatrogon for up to 9 years. MAIN OUTCOME MEASURE(S): : Safety endpoints included adverse events (AEs), antidrug antibodies (ADAs), local site injection reactions, and insulin-like growth factor-I SDS. Efficacy endpoints included annual height velocity (HV), change in height SDS, and annual bone maturation. RESULTS: Treatment-emergent AEs (TEAEs) incidence was 52.1% at OLE year (Y) 1, decreasing to 23.8% by Y9. Serious AEs were rare with only isolated cases reported. ADA positivity was observed, but no neutralizing antibodies were found. No correlation between ADA presence and TEAE incidence or severity was noted, nor was there a difference in growth based on ADA presence. Mean annualized HV remained > 5 cm/year, and height SDS improved from -4.0 at baseline to -0.2 by Y8. No changes in the ratio of bone age/chronological age were observed. CONCLUSIONS: Once-weekly somatrogon is a well-tolerated and a viable long-term treatment for GHD in children. More real-world data are needed. Clinicaltrials.gov: NCT01592500.