SAT-LB15 24-Month Efficacy and Safety of Once Weekly and Every Other Week Administration of GX-H9, Hybrid FC-Fused Long-Acting Human Growth Hormone: A Phase 2 Study in Children With Growth Hormone Deficiency

Abstract

Objectives GX-H9 is a long-acting form of recombinant human GH under clinical development for both adults and children with GHD. In this report, 24-month efficacy and safety of once weekly and every other week (EOW) administration of GX-H9 were evaluated, in addition to Genotropin® switch-ability to GX-H9 after 12-month of treatment. Methods Subjects were randomly assigned to receive either one of three doses of GX-H9 (0.8 mg/kg/week, 1.2 mg/kg/week or 2.4 mg/kg every other week) or 0.03 mg/kg/day of Genotropin®. Treatment duration is 24-month for all patients in GX-H9 arms while patients in Genotropin® arm were re-randomized to one of three doses of GX-H9 at the completion of the first 12-month of treatment. Doses of GX-H9 were adjusted throughout the treatment period whenever necessary, based on IGF-1 levels. Results Out of 56 randomized, 54 received either GX-H9 or Genotropin®. Fifty subjects completed the 12-month treatment period. Of 50, 45 subjects completed the next 12-month, comprising 33 patients from GX-H9 and 12 patients who switched from Genotropin®. First year/second year mean±SD annualized height velocity (aHV) for 0.8 mg/kg/week, 1.2 mg/kg/week or 2.4 mg/kg every other week of GX-H9 were 10.50±2.54/9.14±1.96, 11.76±1.96/9.88±1.92 and 11.03±2.92/9.72±1.90 cm/year, respectively. First year mean±SD aHV for Genotropin® was 9.14±3.09 cm/year. Patients switched to one of the three doses of GX-H9 in the second year showed comparable aHV in the second year (8.73±2.69/7.60±0.90/9.13±1.07 cm/year for 0.8 mg/kg/week, 1.2 mg/kg/week and 2.4 mg/kg/EOW GX-H9, respectively). No significant slow-down of the growth was observed in the second year from patients who received GX-H9 throughout and patients who switched from Genotropin®. Mean change in height SDS after 12 months/24 months of GX-H9 treatment throughout from baseline treatment improved continuously (+1.10/+1.61 and +1.31/+1.89 and +1.15/+1.69 for 0.8 mg/kg/week, 1.2 mg/kg/week and 2.4 mg/kg EOW GX-H9, respectively). First year mean change in height SDS for Genotropin® was +0.92 SDS, and showed comparable improvement in height SDS after switching to GX-H9 weekly arms (+0.76 and +0.79 SDS for 0.8 mg/kg/week and 1.2 mg/kg/week, respectively). Most treatment-emergent adverse events were evaluated as unrelated to the study drug and were mild or moderate in severity. No new safety concerns were observed throughout 24 months of long-term GX-H9 treatment or after switching to GX-H9 from Genotropin®.Conclusions Growth response and safety profile of GX-H9 in children with GHD is comparable to those of daily GH, achieving robust growth rates after 24-month treatment. Subjects switched from Genotropin® in the second year, also showed substantial catch-up growth indicated by improvement in height SDS. GX-H9 has a unique potential to be a convenient long-term GH providing not only weekly but also twice-monthly treatment.

Growth hormone receptor agonists and antagonists: From protein expression and purification to long‐acting formulations

“…Somatrogon is a long‐acting GH fused to three copies of the carboxyl‐terminal peptides derived from the human chorionic gonadotropin, currently used for treating pediatric GHD as a once‐weekly subcutaneous injection (Deal et al, 2022 ; Horikawa et al, 2022 ). Other versions of fusion proteins are currently under development at various stages of clinical trials: GX–H9 (Genexine and Handok), a long‐acting GH fused to a hybrid Fc which consists of noncytolytic IgD and IgG4 (Ku et al, 2018 ; Malievskiy et al, 2020 ); JR‐142 (JCR Pharmaceuticals), a long‐acting GH fused to a modified HSA (Japan Registry of Clinical Trials, 2021); LAPS rhGH (HM10560A; Hanmi Pharmaceutical Co), a long‐acting GH conjugated to recombinant immunoglobulin G4 Fc fragment ( clinicaltrials.gov , HM10560A).…”

Long-Acting Growth Hormone Preparations and Their Use in Children with Growth Hormone Deficiency

“…GX-H9 is a rhGH fused to the Fc portions of IgD and immunoglobulin G 4. Phase 2 dose-find-ing trial in children with GHD reported a comparable efficacy and safety of GX-H9 to daily rhGH [27]. Finally, Somavartan (VRS-317) from Versartis reached a phase 3 study level in children with GHD but was no longer developed after the study proved it to be inferior to daily rhGH in increasing HV and height SDS [28].…”

Основні Наукові Досягнення Відділу Дитячої Ендокринної Патології ДУ «Інститут Ендокринології Та Обміну Речовин Ім. В.П. Комісаренка НАМН України» Як Основа Розвитку Сучасної Української Дитячої Ендокринології

“…Оптимальною стартовою дозою препаратів рГР для лікування хворих на СБНГР є 0,035 мг/кг на добу з подальшим підвищенням дози до 0,05 мг/кг на добу при незадовільному ростовому ефекті. Тривале лікування препаратами рГР в дозі 0,035 мг/кг на добу та 0,05 мг/кг на добу є ефективним і безпечним [70].…”