ESPE Abstracts (2016) 86 RFC8.4

A Hybrid Fc-fused Human Growth Hormone, GX-H9, Shows a Potential for Weekly and Semi-monthly Administration in Clinical Studies

EunJig Leea, Jochen Schopohlb, Aryaev Mykolac, Tae Kyung Kimd, Young-Joo Ahne, Jung-Won Wood, Woo Ick Jange, Young-Chul Sungd & H. Michael Keyoungd

aYonsei University, Seoul, Republic of Korea; bUniversity of Munich Medizinsche Klinik, Munich, Germany; cInstitue of Endocrinology and Metabolism named after Komisarenko NAMS of Ukraine, Kyev, Ukraine; dGenexine, Inc., Seongnam, Republic of Korea; eHandok, Inc., Seoul, Republic of Korea

Background, Objective and hypotheses: GX-H9 is a hybrid Fc-based long-acting recombinant human growth hormone (hGH). The safety, tolerability, and PK/PD of single ascending dose in healthy volunteers were assessed to determine GX-H9 doses capable of normalizing IGF-1 level. The PK/PD, safety, efficacy and tolerability of multiple sequential doses of GX-H9 in adult growth hormone deficiency (AGHD) were compared to that of a daily recombinant hGH in AGHD. A Phase 2 study in pediatric GHD (PGHD) is also ongoing to investigate safety, efficacy and PK/PD of GX-H9.

Method: A double-blind, randomized, placebo-controlled, single ascending dose Phase 1 study of GX-H9 was conducted in 4 groups of healthy subjects (n=32) with four sequential dose levels (0.2, 0.4, 0.8 or 1.6 mg/kg). Currently, a Phase 2, randomized, active-controlled, open-label, sequential dose study of GX-H9 (0.1 mg/kg per weekly, 0.2 and 0.3 mg/kg per semi-monthly) is being conducted in patients with AGHD (n=45). In addition, a Phase 2, randomized, active-controlled, open-label, multiple dose study of GX-H9 with weekly and semi-monthly administrations is being conducted in patients with PGHD (n=48).

Results: Single doses of GX-H9 in the range of 0.2 to 1.6 mg/kg were well tolerated at all dose levels. Only mild adverse events were observed and no lipoatrophy or anti-drug antibodies were detected. Geometric mean of t1/2 ranged between 69.2 and 138.0 hours. IGF-1 serum concentrations increased in a dose-dependent manner between 0.2 and 1.6 mg/kg. The interim Phase 2 results have indicated that AGHD patients (n=11) receiving the lowest dose of GX-H9 (0.1 mg/kg) weekly for 12 weeks were safe and comparable with those receiving 6 μg/kg of Genotropin® daily for 12 weeks (n=2) in the mean increases in IGF-1 (101.3±31.2 ng/mL vs 109.1±45.0 ng/mL, respectively). The administration of higher doses showed potential for semi-monthly treatment of GX-H9 in AGHD and PGHD.

Conclusion: Phase 1 and interim Phase 2 results have demonstrated that GX-H9 is safe and well tolerated in healthy subjects and in patients with AGHD and PGHD. The data from ongoing Phase 2 studies will be presented in addition to the Phase 1 result.