ESPE Abstracts (2019) 92 FC14.4

1Children's Hospital P. A. Kyriakou, Athens, Greece. 2Yerevan State Medical University, Yerevan, Armenia. 3Voronezh State Medical University, Voronezh, Russian Federation. 4Medical University of Gdansk, Gdansk, Poland. 5LTD National Institute of Endocrinology, Tbilisi, Georgia. 6Republican Children's Clinical Hospital of the Ministry of Health of the Udmurt Republic, Izhevsk, Russian Federation. 7Rocky Mountain Pediatric Endocrinology, Centennial, USA. 8Cook Children's, Ft Worth, USA. 9 University of Auckland, Auckland, New Zealand. 10Ascendis Pharma Inc, Palo Alto, USA

Background: TransCon hGH is a sustained-release prodrug in development as a long-acting GH for children with growth hormone deficiency (GHD). TransCon hGH consists of a parent drug, growth hormone (hGH; somatropin), that is transiently bound to a carrier via a TransCon linker. The carrier extends hGH circulation time in the body and fully active hGH is released over one week at physiologic pH and temperature. Unlike other molecules in development, TransCon hGH is designed to deliver unmodified hGH with the same mode-of-action and distribution as daily hGH replacement therapy but with convenient once-weekly dosing.

The aim of the pivotal phase 3 global heiGHt trial was to investigate the safety, tolerability, and efficacy of weekly TransCon hGH versus daily hGH over 52 weeks in treatment-naive prepubertal children with GHD.

Methods: Subjects (N = 161) were randomized 2:1 to receive once-weekly TransCon hGH 0.24 mg hGH/kg/wk or dose-equivalent once-daily Genotropin. The primary endpoint was annualized height velocity (AHV) at 52 weeks, and the trial was powered to demonstrate non-inferiority.

Results: Baseline demographics were similar between the two groups. AHV at 52 weeks was 11.2 cm/y for the TransCon hGH group vs. 10.3 cm/y for the daily Genotropin group (P = 0.0088), with TransCon hGH demonstrating both non-inferiority and superiority over Genotropin. IGF-1 standard deviation score (SDS) was generally within the normal range following treatment for each group. Over 52 weeks, the bone age/chronological age ratio (BA/CA) increased in both groups: by 0.06 to 0.75 for TransCon hGH, and by 0.05 to 0.76 for Genotropin. Bone age advancement was similar in both groups: by 0.17 to 2.33 years for TransCon hGH, and by 0.17 to 2.13 years for Genotropin. TransCon hGH was generally safe and well-tolerated, with adverse events consistent with the type and frequency observed with daily Genotropin. No neutralizing antibodies were detected, and the low level of low-titer non-neutralizing antibodies was similar between groups. Additional analyses will include efficacy by subgroups (e.g., age, gender, baseline stimulated GH strata, GHD etiology and extent), and glycemic and hormonal parameters over time.

Conclusions: In the phase 3 heiGHt trial, treatment with TransCon hGH achieved the primary objective of non-inferiority in AHV at 52 weeks, and further showed superiority over Genotropin. These results suggest that TransCon hGH may offer a convenient alternative, once-weekly hGH therapy for children with GHD, while maintaining a similar safety profile to daily hGH.

Volume 92

58th Annual ESPE

Vienna, Austria
19 Sep 2019 - 21 Sep 2019

European Society for Paediatric Endocrinology 

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