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

doi:10.1016/j.medj.2024.11.019

. 2024 Dec 30:100566.

doi: 10.1016/j.medj.2024.11.019. Online ahead of print.

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

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

Free article

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

Ravi Savarirayan et al. Med. 2024.

Free article

. 2024 Dec 30:100566.

doi: 10.1016/j.medj.2024.11.019. Online ahead of print.

Authors

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.

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Conflict of interest statement

Declaration of interests All authors were investigators in this clinical trial except for S.L., A.L., I.S., A.H.-L., and J.R.S.D., who are employees of the funder (BioMarin). A.L.-G. has received consulting fees from BioMarin, has participated as a clinical trial investigator for BioMarin and QED Therapeutics, has received speaker fees from BioMarin, MBA, and EAF, and has received travel support from BioMarin and MBA. C.A.B. has received consulting fees from BioMarin and has participated as a clinical trial investigator for Ascendis, BioMarin, and Roche. C.E.P. has received consulting fees from BioMarin, Sanofi, and Takeda, has participated as a clinical trial investigator for BioMarin, Hemoshear, Prevail, and Sanofi, and has received speaker payments from Sanofi. J.E.H.-F. has received consulting fees from Ascendis, BioMarin, Innoskel, QED Therapeutics, and Tyra, has received research grants from Alexion, has participated as a clinical trial investigator for BioMarin, QED Therapeutics, and Pfizer/Therachon, has received speaker fees from Medscape, and has received travel support from BioMarin, QED Therapeutics, and Tyra. J.M.L. has received speaker fees and travel support from BioMarin and has participated as a clinical trial investigator for Ascendis and QED Therapeutics/Bridge Bio. K.P. has received consulting payments from BioMarin, Novo Nordisk, and QED Therapeutics, has participated as a clinical trial investigator for BioMarin, and has received speaker fees and travel support from BioMarin and Novo Nordisk. L.E.P. has received consulting fees from BioMarin, Denali, and Lysogene, has participated as a clinical trial investigator for BioMarin, Pfizer, and Takeda, and has received travel support from BioMarin. M.I. has received consulting fees from Ascendis, BioMarin, QED Therapeutics/Bridge Bio, Sanofi, and Tyra, has participated as a clinical trial investigator for Ascendis, BioMarin, and QED Therapeutics/Bridge Bio, has received speaker fees from Ascendis, BioMarin, Ipsen, QED Therapeutics/Bridge Bio, and Sandoz, and has received travel support from Ascendis, BioMarin, and QED Therapeutics/Bridge Bio. M.B.B. has been an employee and shareholder of Tyra Biosciences, has received consultancy fees from BioMarin, QED Therapeutics/Bridge Bio, and Tyra Biosciences, has received research funding (to his institution) from BioMarin, has participated as a clinical trial investigator for Ascendis, BioMarin, QED Therapeutics/Bridge Bio, and Therachon/Pfizer, and has received speaker fees from Novo Nordisk. P.H. has received consultancy fees from Grace Science, Neurogene, Novel Pharma, Orchard Therapeutics, and Rallybio, has received speaker fees, travel support, and travel grants from BioMarin, has received research funding from Adrenas, Allievex, Amicus, Ascendis, ASPA, Azafaros, BioMarin, Calcilytics, Denali, Grace Science, Homology, Idorsia, JCR Pharmaceuticals, Orphazyme, Prevail, QED Therapeutics, RegenXbio, Sangamo, and Takeda, and has participated as a clinical trial investigator for BioMarin. R.S. has received consulting fees and travel support from Ascendis, BioMarin, and QED Therapeutics and has participated as a clinical trial investigator for Ascendis, BioMarin, QED Therapeutics, and Sanofi. T.K. has received speaker payments from BioMarin and Novo Nordisk and research grants from Eli Lilly. W.R.W. has received consulting fees from BioMarin and has participated as a clinical trial investigator for BioMarin.

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

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

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Conflict of interest statement

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