Growth response with once-weekly LB03002 in GH-deficient children is comparable to that with daily GH, achieving expected growth rates for 24 months. Once-weekly LB03002 is a strong candidate for long-term GH replacement in GH-deficient children.

LB03002 at doses of 0.5 mg/kg/wk and 0.7 mg/kg/wk was shown to be effective and safe with once-weekly dosing in GH-deficient children, and 0.5 mg/kg/wk LB03002 was chosen as the optimal dose for long-term assessment.

Hunter syndrome is an X-linked lysosomal storage disease caused by a deficiency in the enzyme iduronate-2-sulfatase (IDS), leading to the accumulation of glycosaminoglycans (GAGs). Two recombinant enzymes, idursulfase and idursulfase beta are currently available for enzyme replacement therapy for Hunter syndrome. These two enzymes exhibited some differences in various clinical parameters in a recent clinical trial. Regarding the similarities and differences of these enzymes, previous research has characterized their biochemical and physicochemical properties. We compared the in vitro and in vivo efficacy of the two enzymes on patient fibroblasts and mouse model. Two enzymes were taken up into the cell and degraded GAGs accumulated in fibroblasts. In vivo studies of two enzymes revealed similar organ distribution and decreased urinary GAGs excretion. Especially, idursulfase beta exhibited enhanced in vitro efficacy for the lower concentration of treatment, in vivo efficacy in the degradation of tissue GAGs and improvement of bones, and revealed lower anti-drug antibody formation. A biochemical analysis showed that both enzymes show largely a similar glycosylation pattern, but the several peaks were different and quantity of aggregates of idursulfase beta was lower.

Weekly GH replacement with the sustained-release preparation LB03002 in adults significantly reduced FM over 6 months and was well tolerated.

Objective: LB03002 is a novel, sustained-release recombinant human GH, developed for once-a-week s.c. injection. To evaluate the suitability for long-term GH replacement therapy in children with GH deficiency (GHD), the present study assessed the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of LB03002 at three doses. Study design and patients: The randomised, comparator-controlled, assessor-blinded, phase II study assessed 37 (24 boys, 13 girls) pre-pubertal, GH-naïve children with GHD, in 11 European centres, for PK and PD analyses. GH, IGF1 and IGFBP3 concentrations were measured following the last daily GH dose and the first and 13th once-a-week administration of LB03002 at doses of 0.2, 0.5 or 0.7 mg/kg. Results: GH C max values after the three doses of LB03002 were increased up to fourfold, with a clear dose proportionality. For each LB03002 dose, GH area under the concentration versus time curve did not increase from the first to 13th (month 3) administration, indicating no accumulation of circulating GH. IGF1 C max showed a progressive increase during LB03002 administration. Conversely, IGFBP3 showed a rapid increase in C max . IGF1 SDS were fully normalised after 3 months of treatment, whereas IGFBP3 SDS were already in the normal range for all the three LB03002 dosages after 1 week. Conclusions: At the doses used, LB03002 has a suitable profile for long-term treatment to promote growth in children with GHD. The quantitative changes in IGF1 and IGFBP3 indicate adequate stimulation of the IGF system by LB03002 and the pattern of increase is comparable with that seen in GHD children in a standard IGF1 generation test using daily GH.