016–TransCon GH as a Long-Acting Growth Hormone for the Treatment of Pediatric Growth Hormone Deficiency

Abstract

Background: With growth hormone (GH) receptors present on virtually all cells, GH replacement therapy should aim for the same exposure and tissue distribution as endogenous GH and current daily GH therapies. The challenge to developing a long-acting GH (LAGH) is to establish the same safety, efficacy, and tolerability of daily GH, which includes maintaining GH and IGF-1 levels within the physiological range. To create a LAGH, two approaches have been used: 1) combine unmodified GH with a prolongation technology, or 2) modify GH providing a longer half-life. TransCon GH is a LAGH prodrug in development for pediatric growth hormone deficiency (GHD) with GH transiently bound to an inert carrier. It was designed to release unmodified GH over 7 days to achieve the same exposure, safety, efficacy, and tolerability as daily GH with more convenient once weekly dosing. This profile was successfully demonstrated in the Phase 2 trial in pediatric GHD. TransCon GH is also being developed with an autoinjector for ease of administration and improved adherence. Aims: We aim to present the topline 52-week pivotal Phase 3 results of TransCon GH in treatment of pediatric GHD. Methods: The phase 3 heiGHt trial was designed to compare safety, tolerability, and efficacy of weekly TransCon GH versus daily GH over 52 weeks in treatment-naive prepubertal children with GHD. Study endpoints include annualized height velocity (AHV), IGF-1 response, immunogenicity, and safety. Results: Top-line 52-week results of the heiGHt trial (N = 161) including AHV, Δ height SDS, IGF-1 levels, Δ bone age, and adverse events, will be available for presentation at PENS 2019. Conclusions: Only LAGHs based on unmodified GH have succeeded in providing both accelerated height velocity as well as reducing truncal adiposity in line with currently available daily GH therapies. Top-line data from the pivotal heiGHt trial of TransCon GH, a LAGH prodrug releasing unmodified GH, will be available in March 2019. Clinical Implications: A GH prodrug that provides sustained release of unmodified GH for the treatment of pediatric GHD would likely maintain the same tissue distribution as endogenous GH, with comparable efficacy, safety, tolerability, with the benefit of improved compliance due to weekly dosing via an autoinjector.