Safe and persistent growth-promoting effects of vosoritide in children with achondroplasia: 2-year results from an open-label, phase 3 extension study

Ravi Savarirayan; Louise Tofts; Melita Irving; William R. Wilcox; Carlos A. Bacino; Julie Hoover-Fong; Rosendo Ullot Font; Paul Harmatz; Frank Rutsch; Michael B. Bober; Lynda E. Polgreen; Ignacio Ginebreda; Klaus Mohnike; Joel Charrow; Daniel Hoernschemeyer; Keiichi Ozono; Yasemin Alanay; Paul Arundel; Yumiko Kotani; Natsuo Yasui; Klane K. White; Howard M. Saal; Antonio Leiva-Gea; Felipe Luna-González; Hiroshi Mochizuki; Donald Basel; Dania M. Porco; Kala Jayaram; Elena Fisheleva; Alice Huntsman-Labed; Jonathan R.S. Day

doi:10.1038/s41436-021-01287-7

Safe and persistent growth-promoting effects of vosoritide in children with achondroplasia: 2-year results from an open-label, phase 3 extension study

Ravi Savarirayan^*, Louise Tofts, Melita Irving, William R. Wilcox, Carlos A. Bacino, Julie Hoover-Fong, Rosendo Ullot Font, Paul Harmatz, Frank Rutsch, Michael B. Bober, Lynda E. Polgreen, Ignacio Ginebreda, Klaus Mohnike, Joel Charrow, Daniel Hoernschemeyer, Keiichi Ozono, Yasemin Alanay, Paul Arundel, Yumiko Kotani, Natsuo YasuiKlane K. White, Howard M. Saal, Antonio Leiva-Gea, Felipe Luna-González, Hiroshi Mochizuki, Donald Basel, Dania M. Porco, Kala Jayaram, Elena Fisheleva, Alice Huntsman-Labed, Jonathan R.S. Day

^*Corresponding author for this work

Pediatrics

Research output: Contribution to journal › Article › peer-review

72 Scopus citations

Abstract

Purpose: Achondroplasia is caused by pathogenic variants in the fibroblast growth factor receptor 3 gene that lead to impaired endochondral ossification. Vosoritide, an analog of C-type natriuretic peptide, stimulates endochondral bone growth and is in development for the treatment of achondroplasia. This phase 3 extension study was conducted to document the efficacy and safety of continuous, daily vosoritide treatment in children with achondroplasia, and the two-year results are reported. Methods: After completing at least six months of a baseline observational growth study, and 52 weeks in a double-blind, placebo-controlled study, participants were eligible to continue treatment in an open-label extension study, where all participants received vosoritide at a dose of 15.0 μg/kg/day. Results: In children randomized to vosoritide, annualized growth velocity increased from 4.26 cm/year at baseline to 5.39 cm/year at 52 weeks and 5.52 cm/year at week 104. In children who crossed over from placebo to vosoritide in the extension study, annualized growth velocity increased from 3.81 cm/year at week 52 to 5.43 cm/year at week 104. No new adverse effects of vosoritide were detected. Conclusion: Vosoritide treatment has safe and persistent growth-promoting effects in children with achondroplasia treated daily for two years.

Original language	English (US)
Pages (from-to)	2443-2447
Number of pages	5
Journal	Genetics in Medicine
Volume	23
Issue number	12
DOIs	https://doi.org/10.1038/s41436-021-01287-7
State	Published - Dec 2021

Funding

All authors were investigators in this clinical trial except for D.P., K.J., E.F., A.H.L. and J.D., who are employees of the funder (BioMarin). R.S., L.T., F.R. and K.M. have received consulting fees and grants from BioMarin. M.I. and W.W. have received consulting fees from BioMarin. J.C. and D.B. have received grants from BioMarin. LP and PA have received honoraria from BioMarin. C.B. and P.H. have received consulting fees, honoraria and grants from BioMarin. J.H.F. has received consulting fees from BioMarin, Therachon AG and Ascendis, and grants from BioMarin. M.B. has received consulting fees from and grants from BioMarin, Ascendis, Therachon, QED and Alexion; and grants from BioMarin, Ascendis, Therachon, QED, Medlife, SOBI, and Shire. K.W. has received consulting fees from BioMarin and Sanofi/Genzyme, and grants from BioMarin, Ultragenyx, and Ascendis. The other authors declare no competing interests.

ASJC Scopus subject areas

Genetics(clinical)

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10.1038/s41436-021-01287-7

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Savarirayan, R., Tofts, L., Irving, M., Wilcox, W. R., Bacino, C. A., Hoover-Fong, J., Font, R. U., Harmatz, P., Rutsch, F., Bober, M. B., Polgreen, L. E., Ginebreda, I., Mohnike, K., Charrow, J., Hoernschemeyer, D., Ozono, K., Alanay, Y., Arundel, P., Kotani, Y., ... Day, J. R. S. (2021). Safe and persistent growth-promoting effects of vosoritide in children with achondroplasia: 2-year results from an open-label, phase 3 extension study. Genetics in Medicine, 23(12), 2443-2447. https://doi.org/10.1038/s41436-021-01287-7

@article{c7f9f945f1684e2798cdaaa0ad8dae5e,

title = "Safe and persistent growth-promoting effects of vosoritide in children with achondroplasia: 2-year results from an open-label, phase 3 extension study",

abstract = "Purpose: Achondroplasia is caused by pathogenic variants in the fibroblast growth factor receptor 3 gene that lead to impaired endochondral ossification. Vosoritide, an analog of C-type natriuretic peptide, stimulates endochondral bone growth and is in development for the treatment of achondroplasia. This phase 3 extension study was conducted to document the efficacy and safety of continuous, daily vosoritide treatment in children with achondroplasia, and the two-year results are reported. Methods: After completing at least six months of a baseline observational growth study, and 52 weeks in a double-blind, placebo-controlled study, participants were eligible to continue treatment in an open-label extension study, where all participants received vosoritide at a dose of 15.0 μg/kg/day. Results: In children randomized to vosoritide, annualized growth velocity increased from 4.26 cm/year at baseline to 5.39 cm/year at 52 weeks and 5.52 cm/year at week 104. In children who crossed over from placebo to vosoritide in the extension study, annualized growth velocity increased from 3.81 cm/year at week 52 to 5.43 cm/year at week 104. No new adverse effects of vosoritide were detected. Conclusion: Vosoritide treatment has safe and persistent growth-promoting effects in children with achondroplasia treated daily for two years.",

author = "Ravi Savarirayan and Louise Tofts and Melita Irving and Wilcox, {William R.} and Bacino, {Carlos A.} and Julie Hoover-Fong and Font, {Rosendo Ullot} and Paul Harmatz and Frank Rutsch and Bober, {Michael B.} and Polgreen, {Lynda E.} and Ignacio Ginebreda and Klaus Mohnike and Joel Charrow and Daniel Hoernschemeyer and Keiichi Ozono and Yasemin Alanay and Paul Arundel and Yumiko Kotani and Natsuo Yasui and White, {Klane K.} and Saal, {Howard M.} and Antonio Leiva-Gea and Felipe Luna-Gonz{\'a}lez and Hiroshi Mochizuki and Donald Basel and Porco, {Dania M.} and Kala Jayaram and Elena Fisheleva and Alice Huntsman-Labed and Day, {Jonathan R.S.}",

note = "Funding Information: All authors were investigators in this clinical trial except for D.P., K.J., E.F., A.H.L. and J.D., who are employees of the funder (BioMarin). R.S., L.T., F.R. and K.M. have received consulting fees and grants from BioMarin. M.I. and W.W. have received consulting fees from BioMarin. J.C. and D.B. have received grants from BioMarin. LP and PA have received honoraria from BioMarin. C.B. and P.H. have received consulting fees, honoraria and grants from BioMarin. J.H.F. has received consulting fees from BioMarin, Therachon AG and Ascendis, and grants from BioMarin. M.B. has received consulting fees from and grants from BioMarin, Ascendis, Therachon, QED and Alexion; and grants from BioMarin, Ascendis, Therachon, QED, Medlife, SOBI, and Shire. K.W. has received consulting fees from BioMarin and Sanofi/Genzyme, and grants from BioMarin, Ultragenyx, and Ascendis. The other authors declare no competing interests. Publisher Copyright: {\textcopyright} 2021, The Author(s).",

year = "2021",

month = dec,

doi = "10.1038/s41436-021-01287-7",

language = "English (US)",

volume = "23",

pages = "2443--2447",

journal = "Genetics in Medicine",

issn = "1098-3600",

publisher = "Elsevier B.V.",

number = "12",

}

Savarirayan, R, Tofts, L, Irving, M, Wilcox, WR, Bacino, CA, Hoover-Fong, J, Font, RU, Harmatz, P, Rutsch, F, Bober, MB, Polgreen, LE, Ginebreda, I, Mohnike, K, Charrow, J, Hoernschemeyer, D, Ozono, K, Alanay, Y, Arundel, P, Kotani, Y, Yasui, N, White, KK, Saal, HM, Leiva-Gea, A, Luna-González, F, Mochizuki, H, Basel, D, Porco, DM, Jayaram, K, Fisheleva, E, Huntsman-Labed, A & Day, JRS 2021, 'Safe and persistent growth-promoting effects of vosoritide in children with achondroplasia: 2-year results from an open-label, phase 3 extension study', Genetics in Medicine, vol. 23, no. 12, pp. 2443-2447. https://doi.org/10.1038/s41436-021-01287-7

TY - JOUR

T1 - Safe and persistent growth-promoting effects of vosoritide in children with achondroplasia

T2 - 2-year results from an open-label, phase 3 extension study

AU - Savarirayan, Ravi

AU - Tofts, Louise

AU - Irving, Melita

AU - Wilcox, William R.

AU - Bacino, Carlos A.

AU - Hoover-Fong, Julie

AU - Font, Rosendo Ullot

AU - Harmatz, Paul

AU - Rutsch, Frank

AU - Bober, Michael B.

AU - Polgreen, Lynda E.

AU - Ginebreda, Ignacio

AU - Mohnike, Klaus

AU - Charrow, Joel

AU - Hoernschemeyer, Daniel

AU - Ozono, Keiichi

AU - Alanay, Yasemin

AU - Arundel, Paul

AU - Kotani, Yumiko

AU - Yasui, Natsuo

AU - White, Klane K.

AU - Saal, Howard M.

AU - Leiva-Gea, Antonio

AU - Luna-González, Felipe

AU - Mochizuki, Hiroshi

AU - Basel, Donald

AU - Porco, Dania M.

AU - Jayaram, Kala

AU - Fisheleva, Elena

AU - Huntsman-Labed, Alice

AU - Day, Jonathan R.S.

N1 - Funding Information: All authors were investigators in this clinical trial except for D.P., K.J., E.F., A.H.L. and J.D., who are employees of the funder (BioMarin). R.S., L.T., F.R. and K.M. have received consulting fees and grants from BioMarin. M.I. and W.W. have received consulting fees from BioMarin. J.C. and D.B. have received grants from BioMarin. LP and PA have received honoraria from BioMarin. C.B. and P.H. have received consulting fees, honoraria and grants from BioMarin. J.H.F. has received consulting fees from BioMarin, Therachon AG and Ascendis, and grants from BioMarin. M.B. has received consulting fees from and grants from BioMarin, Ascendis, Therachon, QED and Alexion; and grants from BioMarin, Ascendis, Therachon, QED, Medlife, SOBI, and Shire. K.W. has received consulting fees from BioMarin and Sanofi/Genzyme, and grants from BioMarin, Ultragenyx, and Ascendis. The other authors declare no competing interests. Publisher Copyright: © 2021, The Author(s).

PY - 2021/12

Y1 - 2021/12

N2 - Purpose: Achondroplasia is caused by pathogenic variants in the fibroblast growth factor receptor 3 gene that lead to impaired endochondral ossification. Vosoritide, an analog of C-type natriuretic peptide, stimulates endochondral bone growth and is in development for the treatment of achondroplasia. This phase 3 extension study was conducted to document the efficacy and safety of continuous, daily vosoritide treatment in children with achondroplasia, and the two-year results are reported. Methods: After completing at least six months of a baseline observational growth study, and 52 weeks in a double-blind, placebo-controlled study, participants were eligible to continue treatment in an open-label extension study, where all participants received vosoritide at a dose of 15.0 μg/kg/day. Results: In children randomized to vosoritide, annualized growth velocity increased from 4.26 cm/year at baseline to 5.39 cm/year at 52 weeks and 5.52 cm/year at week 104. In children who crossed over from placebo to vosoritide in the extension study, annualized growth velocity increased from 3.81 cm/year at week 52 to 5.43 cm/year at week 104. No new adverse effects of vosoritide were detected. Conclusion: Vosoritide treatment has safe and persistent growth-promoting effects in children with achondroplasia treated daily for two years.

AB - Purpose: Achondroplasia is caused by pathogenic variants in the fibroblast growth factor receptor 3 gene that lead to impaired endochondral ossification. Vosoritide, an analog of C-type natriuretic peptide, stimulates endochondral bone growth and is in development for the treatment of achondroplasia. This phase 3 extension study was conducted to document the efficacy and safety of continuous, daily vosoritide treatment in children with achondroplasia, and the two-year results are reported. Methods: After completing at least six months of a baseline observational growth study, and 52 weeks in a double-blind, placebo-controlled study, participants were eligible to continue treatment in an open-label extension study, where all participants received vosoritide at a dose of 15.0 μg/kg/day. Results: In children randomized to vosoritide, annualized growth velocity increased from 4.26 cm/year at baseline to 5.39 cm/year at 52 weeks and 5.52 cm/year at week 104. In children who crossed over from placebo to vosoritide in the extension study, annualized growth velocity increased from 3.81 cm/year at week 52 to 5.43 cm/year at week 104. No new adverse effects of vosoritide were detected. Conclusion: Vosoritide treatment has safe and persistent growth-promoting effects in children with achondroplasia treated daily for two years.

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U2 - 10.1038/s41436-021-01287-7

DO - 10.1038/s41436-021-01287-7

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AN - SCOPUS:85111805112

SN - 1098-3600

VL - 23

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JO - Genetics in Medicine

JF - Genetics in Medicine

IS - 12

ER -

Safe and persistent growth-promoting effects of vosoritide in children with achondroplasia: 2-year results from an open-label, phase 3 extension study

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