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
{"title":"vosoritide对软骨发育不全儿童的持续生长促进作用：一项正在进行的3期扩展研究。","authors":"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","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Findings: </strong>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.</p><p><strong>Conclusions: </strong>Vosoritide treatment was well tolerated and had sustained growth-promoting effects in children with achondroplasia treated for up to 6 years.</p><p><strong>Funding: </strong>This work was funded by BioMarin Pharmaceutical.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"100566"},"PeriodicalIF":12.8000,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Sustained growth-promoting effects of vosoritide in children with achondroplasia from an ongoing phase 3 extension study.\",\"authors\":\"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\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Findings: </strong>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.</p><p><strong>Conclusions: </strong>Vosoritide treatment was well tolerated and had sustained growth-promoting effects in children with achondroplasia treated for up to 6 years.</p><p><strong>Funding: </strong>This work was funded by BioMarin Pharmaceutical.</p>\",\"PeriodicalId\":29964,\"journal\":{\"name\":\"Med\",\"volume\":\" \",\"pages\":\"100566\"},\"PeriodicalIF\":12.8000,\"publicationDate\":\"2025-05-09\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Med\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1016/j.medj.2024.11.019\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/12/30 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Med","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1016/j.medj.2024.11.019","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/12/30 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
Sustained growth-promoting effects of vosoritide in children with achondroplasia from an ongoing phase 3 extension study.
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.
期刊介绍：
Med is a flagship medical journal published monthly by Cell Press, the global publisher of trusted and authoritative science journals including Cell, Cancer Cell, and Cell Reports Medicine. Our mission is to advance clinical research and practice by providing a communication forum for the publication of clinical trial results, innovative observations from longitudinal cohorts, and pioneering discoveries about disease mechanisms. The journal also encourages thought-leadership discussions among biomedical researchers, physicians, and other health scientists and stakeholders. Our goal is to improve health worldwide sustainably and ethically.
Med publishes rigorously vetted original research and cutting-edge review and perspective articles on critical health issues globally and regionally. Our research section covers clinical case reports, first-in-human studies, large-scale clinical trials, population-based studies, as well as translational research work with the potential to change the course of medical research and improve clinical practice.
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