Z Geburtshilfe Neonatol 2023; 227(S 01): e165-e166
DOI: 10.1055/s-0043-1776484
Abstracts
DGPM

A randomized controlled trial of vosoritide in infants and toddlers with Achondroplasia

L. E. Polgreen
1   Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, Vereinigte Staaten
,
R. Savarirayan
2   Murdoch Children’s Research Institute, Royal Children’s Hospital, and University of Melbourne, Parkville, Australien
,
W. W. Wilcox
3   Emory University, Atlanta, GA, Vereinigte Staaten
,
P. Harmatz
4   UCSF Benioff Children’s Hospital Oakland, Oakland, CA, Vereinigte Staaten
,
J. Phillips
5   Vanderbilt University Medical Center, Nashville, TN, Vereinigte Staaten
,
L. Tofts
6   Kids Rehab, The Children's Hospital at Westmead, Westmead, Australien
,
K. Ozono
7   Osaka University Hospital, Osaka, Japan
,
P. Arundel
8   Sheffield Children's NHS Foundation Trust, Sheffield Children's Hospital, Sheffield, Vereinigtes Königreich
,
M. Irving
9   Guy’s and St. Thomas’ NHS Foundation Trust, Evelina Children's Hospital, London, Vereinigtes Königreich
,
C. A. Bacino
10   Baylor College of Medicine, Houston, TX, Vereinigte Staaten
,
D. Basel
11   Medical College of Wisconsin, Milwaukee, WI, Vereinigte Staaten
,
M. B. Bober
12   Nemours /Alfred I. du Pont Hospital for Children, Wilmington, DE, Vereinigte Staaten
,
J. Charrow
13   Ann and Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL, Vereinigte Staaten
,
H. Mochizuki
14   Saitama Children’s Hospital, Saitama, Japan
,
Y. Kotani
15   Tokushima University Hospital, Tokushima, Japan
,
H. M. Saal
16   Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, Vereinigte Staaten
,
G. Jeha
17   BioMarin Pharmaceutical Inc., Novato, CA, Vereinigte Staaten
,
L. Han
17   BioMarin Pharmaceutical Inc., Novato, CA, Vereinigte Staaten
,
E. Fisheleva
18   BioMarin (U.K.) Limited, London, Vereinigtes Königreich
,
A. Huntsman-Labed
18   BioMarin (U.K.) Limited, London, Vereinigtes Königreich
,
J. Day
18   BioMarin (U.K.) Limited, London, Vereinigtes Königreich
,
S. Groß-Layh
19   BioMarin Deutschland GmbH, Kronberg/Ts., Deutschland
› Author Affiliations
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    Objectives Vosoritide increases annualized growth velocity (AGV) in children with achondroplasia aged 5 to 18 years. This global, phase 2, randomized, double-blind, placebo-controlled study evaluated the safety and efficacy of vosoritide on growth in children with achondroplasia aged 3 months to<5 years.

    Methods This study compared once-daily subcutaneous administration of vosoritide, at doses of 15 or 30 µg/kg of body weight, with placebo. Eligible patients had participated, for up to 6 months, in an observational growth study to calculate their baseline AGV. The primary objective was to evaluate the safety and tolerability of vosoritide in children with achondroplasia. The primary efficacy evaluation was the change from baseline in height Z-score versus placebo at week 52 using an ANCOVA model. Secondary efficacy analyses included change from baseline in AGV and upper-to-lower body segment ratio versus placebo at Week 52 using an ANCOVA model.

    Results A total of 75 patients were enrolled in three sequential cohorts based on age at screening, with 11 sentinel subjects who received vosoritide to establish PK and safety. A further 32 were randomized to receive vosoritide and 32 to receive placebo. A total of 73 patients completed the 52-week trial. All patients reported at least one adverse event. Four serious adverse events occurred with vosoritide and 8 with placebo, none were treatment-related. Two participants discontinued, one on vosoritide with preexisting respiratory morbidity who had a fatal respiratory arrest and one on placebo who withdrew consent. In the full analysis population, vosoritide (n=43) compared to placebo (n=32) increased height Z-score by 0.30 SD (95% CI 0.07, 0.54), increased AGV by 0.92cm/year (95% CI 0.24, 1.59), and did not worsen upper-to-lower body segment ratio which changed by -0.06 (95% CI -0.15, 0.03). The increases in height Z-score and AGV were consistent across all age cohorts.

    Conclusions Daily, subcutaneous administration of vosoritide to young children with achondroplasia was safe and resulted in increases in height Z-score and AGV.


     

    Publication History

    Article published online:
    15 November 2023

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