Results From an Open-Label Extension of the Phase 2 Dose Finding Study of Once Weekly Somatrogon vs Daily Genotropin in Pediatric Patients With Growth Hormone Deficiency (GHD)
Authors: Zadik Zvi , Zelinska Nataliya , Iotova Violeta , Skorodok Yulia , Malievskiy Oleg A , Mauras Nelly , Valluri Srinivas R , Pastrak Aleksandra , Rosenfeld Ron G 
Published: May 2021

Abstract
Background: Somatrogon, a long-acting recombinant human growth hormone, is being developed as a once weekly treatment for pediatric patients (pts) with GHD. A phase 2, 12 month study (NCT01592500) in pts with GHD showed that weekly somatrogon at 0.66 mg/kg/week had similar efficacy and safety to daily Genotropin. Pts who completed 12 months of treatment could be enrolled into an open-label extension (OLE).
Aims: Evaluate the safety and efficacy of long-term exposure to somatrogon in pediatric pts with GHD who continued in the OLE for up to an additional 5 years.
Methods: Methods for the main phase 2 study were published previously (Zelinska et al, 2017), in which 53 pts were randomized to 1 of 3 weekly somatrogon dose cohorts (0.25, 0.48, and 0.66 mg/kg/week) or the daily Genotropin cohort (0.24 mg/kg/week) for 12 months. After the main study (Periods I/II), 48 pts who consented to participate continued in the OLE, consisting of 3 periods: Period III=12 additional months at original somatrogon dose (Genotropin recipients randomized to 1 of the 3 somatrogon dose regimens); Period IV=subsequent years 2-4 with all pts receiving somatrogon at 0.66 mg/kg/week; Period V=ongoing, with pts transitioned from the vial to a pre-filled pen device at the same somatrogon dose (0.66 mg/kg/week). Data up to 1 year of Period V are reported.
Results: Overall subject retention in different periods of this long-term study ranged from 87.5% to 97.7%. 39 pts (81.3%) reported at least one treatment-emergent adverse event (TEAE). Most TEAEs were mild or moderate in intensity and most were classified as unrelated to study treatment. 3 pts (6.3%) reported at least 1 serious adverse event (SAE); most SAEs were considered unrelated to study treatment, except for 1 instance of scoliosis. At the end of Period III, the mean annual height velocity (HV) was similar for the 0.25 and 0.48 mg/kg/week dose cohorts (7.73±1.89 and 7.54±1.28 cm/year, respectively) but was higher in the 0.66 mg/kg/week dose cohort (8.81±1.12 cm/year), consistent with the results of the main study. The HV at Periods IV and V showed sustained growth response. Height SDS showed consistent improvement and near normalization of height for age and gender after up to 6 years on somatrogon, irrespective of initial cohort assignment; height SDS at baseline of the main study was -3.98±1.22 and was well within the normal range at -0.69±0.87 at the end of Year 1 in Period V. IGF-1 SDS values remained above baseline and were maintained within the therapeutic target range with weekly somatrogon treatment at all time points in all OLE periods. Anti-drug antibodies (ADAs) were reported in 18 pts, of which 10 pts had ADAs in the main study. The presence of ADAs did not impact efficacy or safety.
Conclusions: Somatrogon administered once weekly for up to 5 years after the main study was generally well tolerated and participants showed sustained improvement in annual HV, height SDS, and delta height SDS.