ESPE Abstracts (2016) 86 RFC8.8

Efficacy of Once-Weekly Administration of CTP-Modified Human Growth Hormone (MOD-4023): 24-month Complete Database Results of a Phase 2 Study in Children with Growth Hormone Deficiency

Nataliya Zelinskaa, Julia Skorodokb, Oleg Malievskyc, Ron G. Rosenfeldd, Zvi Zadike, Ronit Korenf, Shelly Vanderf, Gili Hartf & Dmitri Radukg

aUkrainian Children Specialized Clinical Hospital, Kyev, Ukraine; bSt. Petersburg State Pediatric Medical Academy, St. Petersburg, Russia; cBashkir State Medical University, Ufa, Russia; dOregon Health & Science University, Oregon, USA; eKaplan Medical Center, Rehovot, Israel; fOPKO Biologics, Nes Ziona, Israel; g2nd Children City Clinic, Minsk, Belarus

Background: Growth hormone (GH) replacement therapy currently requires daily injections, which may cause poor compliance, inconvenience and distress for patients. CTP-modified hGH (MOD-4023) has been developed by OPKO Biologics for once-weekly administration in growth hormone-deficient (GHD) adults and children.

Objective and hypotheses: The 24-month efficacy of once-weekly subcutaneous (SC) administration of MOD-4023 was evaluated in a Phase 2 study in GHD children.

Method: A randomized, controlled Phase 2 study was conducted in prepubertal children with GHD receiving once-weekly SC injections of one of three MOD-4023 doses (0.25, 0.48, and 0.66 mg/kg per week) vs daily hGH (34 μg/kg per day). Subjects were rolled over to continue with the same MOD-4023 dose in an open-label extension (OLE), which will routinely assess growth until marketing approval. Height velocity (HV) results during the 2nd year of MOD-4023 treatment were compared to historical controls (Ranke et al., 2010), and IGF-1 and IGFBP-3 levels were monitored as well.

Results: The height velocity analysis included the full dataset for patients who completed 24 months of treatment. All 3 doses of MOD-4023 demonstrated promising 2nd year growth, while the two higher doses of MOD-4023 resulted in better growth in comparison to the lower dose of MOD-4023 (0.25 mg/kg per week), and in line with reported age- and GHD severity-matched historical control (Ranke et al., 2010).

Conclusion: The efficacy of single weekly MOD-4023 administration for the treatment of pediatric GHD was further confirmed during the 2nd year of treatment as part of the OLE of a Phase 2 study. This further affirms that a single weekly MOD-4023 injection has the potential to replace daily hGH in GHD children. Based on the above, a pivotal Phase 3 study will be initiated shortly at a dose of 0.66 mg/kg per week, and patients receiving the lower MOD-4023 doses will be switched to the 0.66 mg/kg per week dose for long-term assessment.