Vosoritide Therapy in Children with Achondroplasia: Early Experience and Practical Considerations for Clinical Practice

Semler, Oliver; Cormier-Daire, Valérie; Lausch, Ekkehart; Bober, Michael B.; Carroll, Ricki; Sousa, Sérgio B.; Deyle, David; Faden, Maha; Hartmann, Gabriele; Huser, Aaron J.; Legare, Janet M.; Mohnike, Klaus; Rohrer, Tilman R.; Rutsch, Frank; Smith, Pamela; Travessa, Andre M.; Verardo, Angela; White, Klane K.; Wilcox, William R.; Hoover-Fong, Julie

doi:10.1007/s12325-023-02705-9

Cited by 9 publications

(3 citation statements)

References 30 publications

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“…The recombinant human CNP analogue, possessing a modi ed N-terminal domain and resembling CNP in its pharmacological action as an endogenous positive regulator of endochondral bone formation, explains this. It has the capability to obstruct the downstream signaling of the constitutively active FGFR3, thereby reinstating chondrocyte differentiation, enhancing bone growth, and enhancing growth outcomes [11,[24][25]. 100% of panel experts agreed that starting vosoritide treatment earlier and for longer-term results in a greater nal height compared to those starting later [22].…”

Section: 1: the Effect Of Vosoritide In Different Doses On Height Z-s...mentioning

confidence: 99%

“…Vosoritide, a modi ed human recombinant CNP analog, binds to the receptor to raise the level of cyclic guanosine monophosphate (cGMP) inside cells, stopping the FGFR3 signalling cascade [10]. The European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) approved Vosoritide in 2021 for the treatment of ACH children with open epiphyses who are ≥ 5 years old in the United States of America (USA), ≥ 2 years old in the European Union (EU), Brazil, and Australia, and from birth in Japan [11]. Vosoritide expanded the previously restricted range of ACH treatment options.…”

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confidence: 99%

“…Providers must inform patients and their families about the data from the vosoritide clinical trial. International consensus guidance is required to support the use of vosoritide in clinical practice [11][12][13].…”

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confidence: 99%

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Efficacy and Safety of Vosoritide for Achondroplasia: A Systematic Review and Dose- Related Meta-Analysis, 2024 Article type: Systematic review and Dose-related Meta-analysis

Khan,

Akhtar,

Zulfiqar

et al. 2024

Preprint

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Background Achondroplasia, the most common form of dwarfism, poses significant medical and psychosocial challenges. Vosoritide, a new C-type natriuretic peptide analog, has shown promise in treating achondroplasia by helping bones grow. Therefore, we conducted this study to examine the effect of different vosoritide doses on height from baseline (z-score), annualized growth velocity (AGV), the upper-to-lower body segment ratio (ULBR), and side effects. changes in growth velocity and the frequency of adverse effects. Methods This systematic review and dose-related meta-analyses follow the PRISMA guidelines, which meticulously screen and extract randomized controlled trials (RCTs) from four databases until April 2024 involving 220 patients. We used pairwise meta-analyses and assessed quality using the Cochrane Risk of Bias Tool. Results Higher Vosoritide doses (15 µg/kg or 15–30 µg/kg) showed significantly greater improvements in height z-scores compared to lower doses (2.5 µg/kg or 7.5 µg/kg) or placebo. We observed similar trends for AGV. The 15 µg/kg dose displayed a significantly greater increase compared to both 2.5 µg/kg and 7.5 µg/kg. Interestingly, no significant difference was found between the 15 µg/kg and 30 µg/kg groups, suggesting a possible plateau effect at higher doses. Importantly, both the 15 µg/kg and 15–30 µg/kg groups demonstrated statistically significant improvements in growth velocity compared to placebo. While most comparisons showed no significant changes in ULBR, one study reported a small increase in ULBR with the 15 µg/kg dose compared to the 2.5 µg/kg dose. Adverse effects were mild to moderate across all studies, with no severe effects reported. Conclusion Vosoritide improves achondroplasia growth in a dose-dependent manner. Higher doses (15 µg/kg or 15–30 µg/kg) significantly increased height and growth velocity compared to lower doses or placebo. All adverse effects were mild to moderate. However, the impact on the ULBR and adverse effects require further investigation.

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