ESPE Abstracts (2023) 97 FC4.6

1Murdoch Children’s Research Institute, Royal Children’s Hospital, and University of Melbourne, Parkville, Australia. 2Guy’s and St. Thomas’ NHS Foundation Trust, Evelina Children's Hospital, London, United Kingdom. 3Department of Human Genetics, Emory University, Atlanta, USA. 4UCSF Benioff Children’s Hospital Oakland, Oakland, USA. 5Vanderbilt University Medical Center, Nashville, USA. 6Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, USA. 7Kids Rehab, The Children's Hospital at Westmead, Westmead, Australia. 8Osaka University Hospital, Osaka, Japan. 9Sheffield Children's NHS Foundation Trust, Sheffield Children's Hospital, Sheffield, United Kingdom. 10Baylor College of Medicine, Houston, USA. 11Medical College of Wisconsin, Milwaukee, USA. 12Nemours/Alfred I. du Pont Hospital for Children, Wilmington, USA. 13Ann and Robert H. Lurie Children’s Hospital of Chicago, Chicago, USA. 14Saitama Children’s Hospital, Saitama, Japan. 15Tokushima University Hospital, Tokushima, Japan. 16Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine Cincinnati, Cincinnati, USA. 17BioMarin Pharmaceutical Inc., Novato, USA. 18BioMarin (U.K.) Limited, London, United Kingdom

Introduction: Vosoritide increases growth in children with achondroplasia aged 5–18 years (Savarirayan et al, Genet Med, 2021). We recently reported results from a phase 2, randomized, double-blind, placebo-controlled study (111-206) in young children with achondroplasia aged 3 months–5 years Here we present results from an open-label extension study (111-208) spanning up to 4 years of treatment in the children aged 2-5 years at study start.

Methods: After a 1 year placebo-controlled study with vosoritide at 15 mg/kg body weight (111-206), participants transitioned to open-label treatment (ongoing study 111-208). Results were analysed by age cohort at treatment start (>2 years cohort reported herein). Primary objectives were evaluation of safety and tolerability, and change in height z-score. Height z-scores were referenced to CDC average stature growth charts. Comparative cross-sectional analyses were performed for each year of follow-up based on available data using two independent external controls: (1) observational/placebo data from study 111-901 (Savarirayan et al, Genet Med, 2022) and placebo data from 111-301 (Savarirayan et al, Lancet, 2020) and 111-206 vosoritide trials, and (2) external CLARITY natural history dataset (Hoover-Fong et al, Orphanet, 2021). Changes in upper:lower body segment ratio are expressed in relation to findings from observational/placebo controls.

Results: 34 participants started vosoritide treatment in study 111-206 or 111-208 between ages 2-5 years (56% male, 44% female, mean (SD) age 42.3 (10.11) months). Vosoritide remained well-tolerated with no change in adverse event profile and no discontinuations due to treatment-related adverse events. Changes in height z-score over time in participants are shown in the table. After 4 years, treated children demonstrated greater height gain compared to observational/placebo controls (LS mean change 6.27cm [95% CI 2.98-9.56]) and to matched untreated children from CLARITY (LS mean change 7.77 cm [95% CI 5.14, 10.40]). Compared to observational/placebo controls, improvement in upper:lower body segment ratio was seen after 4 years (LS mean change 0.10 [95% CI -0.19, 0.00]).

Treated versus untreated (Observational/Placebo Control) Treated versus CLARITY
Mean height z-score change 95% CI Mean height z-score change 95% CI
Year 1 (n=34) +0.24 -0.08, 0.56 +0.40 0.21, 0.59
Year 2 (n=30) +0.33 -0.01, 0.66 +0.58 0.34, 0.82
Year 3 (n=22) +0.55 0.17, 0.93 +0.80 0.48, 1.12
Year 4 (n=9) +1.10 0.46, 1.74 +1.42 0.91, 1.93

Conclusions: Vosoritide was well tolerated and maintained positive effects on linear growth over time. Upper:lower body segment ratio improved over time.

Volume 97

61st Annual ESPE (ESPE 2023)

The Hague, Netherlands
21 Sep 2023 - 23 Sep 2023

European Society for Paediatric Endocrinology 

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