Sustained growth-promoting effects of vosoritide in children with achondroplasia from an ongoing phase 3 extension study

Ravi Savarirayan; Melita Irving; William R Wilcox; Carlos A Bacino; Julie E Hoover-Fong; Paul Harmatz; Lynda E Polgreen; Katja Palm; Carlos E Prada; Takuo Kubota; Paul Arundel; Yumiko Kotani; Antonio Leiva-Gea; Michael B Bober; Jacqueline T Hecht; Janet M Legare; Sue Lawrinson; Andrea Low; Ian Sabir; Alice Huntsman-Labed; Jonathan R S Day

doi:10.1016/j.medj.2024.11.019

Sustained growth-promoting effects of vosoritide in children with achondroplasia from an ongoing phase 3 extension study

Med. 2024 Dec 30:100566. doi: 10.1016/j.medj.2024.11.019. Online ahead of print.

Authors

Ravi Savarirayan¹, Melita Irving², William R Wilcox³, Carlos A Bacino⁴, Julie E Hoover-Fong⁵, Paul Harmatz⁶, Lynda E Polgreen⁷, Katja Palm⁸, Carlos E Prada⁹, Takuo Kubota¹⁰, Paul Arundel¹¹, Yumiko Kotani¹², Antonio Leiva-Gea¹³, Michael B Bober¹⁴, Jacqueline T Hecht¹⁵, Janet M Legare¹⁶, Sue Lawrinson¹⁷, Andrea Low¹⁷, Ian Sabir¹⁷, Alice Huntsman-Labed¹⁷, Jonathan R S Day¹⁷

Affiliations

¹ Murdoch Children's Research Institute, Royal Children's Hospital Victoria, University of Melbourne, Parkville, VIC, Australia. Electronic address: ravi.savarirayan@mcri.edu.au.
² Guy's and St. Thomas' NHS Foundation Trust, Evelina Children's Hospital, London, UK.
³ Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA.
⁴ Baylor College of Medicine, Houston, TX, USA.
⁵ Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁶ UCSF Benioff Children's Hospital Oakland, Oakland, CA, USA.
⁷ Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.
⁸ Otto-von-Guericke Universität, Universitätskinderklinik, Magdeburg, Germany.
⁹ Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA.
¹⁰ Osaka University, Osaka, Japan.
¹¹ Sheffield Children's NHS Foundation Trust, Sheffield Children's Hospital, Sheffield, UK.
¹² Tokushima University Hospital, Tokushima, Japan.
¹³ Hospital Universitario Virgen de la Victoria, Instituto de Investigación Biomédica de Málaga, Málaga, Spain.
¹⁴ Nemours-Alfred I. du Pont Hospital for Children, Wilmington, DE, USA.
¹⁵ McGovern Medical School and School of Dentistry, University of Texas Health, Houston, TX, USA.
¹⁶ University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
¹⁷ BioMarin (UK) Limited, Ltd., London, UK.

PMID: 39740666
DOI: 10.1016/j.medj.2024.11.019

Abstract

Background: Vosoritide is a C-type natriuretic peptide analog that addresses an underlying pathway causing reduced bone growth in achondroplasia. Understanding the vosoritide treatment effect requires evaluation over an extended duration and comparison with outcomes in untreated children.

Methods: After completing ≥6 months of a baseline observational growth study and 52 weeks in a double-blind, placebo-controlled study (ClinicalTrials.gov: NCT03197766), participants were eligible to continue treatment in an open-label extension (ClinicalTrials.gov: NCT03424018) wherein all received 15 μg/kg vosoritide daily. Data from the CLARITY achondroplasia study provided an external untreated control population and reference data.

Findings: The population comprised 119 participants. Annualized growth velocity with vosoritide was similar to the average-stature population before puberty. The mean (SD) differences in annualized growth velocity across each integer age (6-16 years) between treated and untreated children were 1.84 (0.38) cm/year in boys and 1.44 (0.63) cm/year in girls. Three-year comparisons of treated versus untreated children demonstrated an additional height gain of 5.75 cm (95% confidence interval [CI]: 4.93, 6.57) with vosoritide. A significant improvement in upper-to-lower body segment ratio at 3 years of treatment was observed for participants with assessments at age <11 (females) and <12 years (males) versus population-level, age-matched, untreated controls (p = 0.0087). The arm span-to-standing height ratio remained consistent with untreated participants. Vosoritide had a favorable safety profile with continuous treatment for up to 6 years (464.05 person years of exposure). No long-term harms or deaths were observed.

Conclusions: Vosoritide treatment was well tolerated and had sustained growth-promoting effects in children with achondroplasia treated for up to 6 years.

Funding: This work was funded by BioMarin Pharmaceutical.

Keywords: Translation to patients; achondroplasia; growth; proportionality; safety; vosoritide.

Associated data

ClinicalTrials.gov/NCT03197766
ClinicalTrials.gov/NCT03424018