Background: OPKO Biologics is developing MOD-4023, a long-acting growth hormone (GH), intended for weekly dosing for the treatment of idiopathic GH deficiency in children. At ESPE2015, we presented pharmacokinetic (PK) and pharmacodynamic (PD, based on IGF-1) models for weekly MOD-4023 administration in children aged 311 years. Those models were based on data collected during the PKPD period (the second steady state dose of MOD-4023) and monthly values during the remainder of the first year of treatment. We now extend those analyses to data collected during the second year of treatment.
Objective and hypotheses: To evaluate whether the PK and PD models developed from data during the first year of treatment with MOD-4023 apply to data during the second year of open-label treatment.
Methods: After one year of treatment, children treated with weekly MOD-4023 continued on the same dose of MOD-4023 (0.25, 0.48, or 0.66 mg/kg); children treated with daily Genotropin were reassigned to one of the three weekly MOD-4023 dose levels. Blood was sampled monthly at ~4 days post-dose to determine concentrations of MOD-4023 and IGF-1. A dataset was assembled that included values through 2 years of treatment. MOD-4023 concentrations were fit to a 2-compartment linear compartmental model. IGF-1 data were fit to an indirect PD model in which MOD-4023 increases input of IGF-1 to plasma, from which there is first-order elimination. We evaluated whether data from the second year was predicted by data from the first year.
Results: Analyses are not yet complete.
Conclusion: Clinical data indicate that efficacy of MOD-4023, particularly at the higher dose levels, is preserved through it least 2 years of treatment. The current analysis will evaluate whether PK and PD characteristics predicted from the first year of treatment are preserved during the second year.
10 Sep 2016 - 12 Sep 2016