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Open Access 23-04-2024 | Achondroplasia | Original Research Article

Development of a Weight-Band Dosing Approach for Vosoritide in Children with Achondroplasia Using a Population Pharmacokinetic Model

Authors: Yulan Qi, Ming Liang Chan, Diane R. Mould, Kevin Larimore, Elena Fisheleva, Anu Cherukuri, Jonathan Day, Ravi Savarirayan, Melita Irving, Carlos A. Bacino, Julie Hoover-Fong, Keiichi Ozono, Klaus Mohnike, William R. Wilcox, Michael B. Bober, Joshua Henshaw

Published in: Clinical Pharmacokinetics | Issue 5/2024

Abstract

Background and Objective

Vosoritide is a recently approved therapy for achondroplasia, the most common form of disproportionate short stature, that has been shown to be well tolerated and effective in increasing linear growth. This study aimed to develop a population pharmacokinetic (PPK) model to characterize pharmacokinetics (PK) of vosoritide and establish a weight-band dosing regimen.

Methods

A PPK model was developed using data from five clinical trials in children with achondroplasia (aged 0.95−15 years) who received daily per-kg doses of vosoritide. The model was used to simulate expected exposures in children with a refined weight-band dosing regimen. Simulated exposure was compared with the observed exposure from the pivotal clinical trial to evaluate appropriateness of the weight-band dosing regimen.

Results

A one-compartment model with a change-point first-order absorption and first-order elimination accurately described PK of vosoritide in children with achondroplasia. Body weight was found to be a predictor of vosoritide’s clearance and volume of distribution. Additionally, it was observed that dosing solution concentration and duration of treatment influenced bioavailability. The weight-band dosing regimen resulted in simulated exposures that were within the range demonstrated to be well tolerated and effective in the pivotal clinical trial and showed improved consistency in drug exposure across the achondroplasia population.

Conclusions

The weight-band dosing regimen reduced the number of recommended dose levels by body weight and is expected to simplify dosing for children with achondroplasia and their caregivers.

Clinical Trial Registration

NCT02055157, NCT02724228, NCT03197766, NCT03424018, and NCT03583697.

Available only for authorised users

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Title: Development of a Weight-Band Dosing Approach for Vosoritide in Children with Achondroplasia Using a Population Pharmacokinetic Model
Authors: Yulan Qi
Ming Liang Chan
Diane R. Mould
Kevin Larimore
Elena Fisheleva
Anu Cherukuri
Jonathan Day
Ravi Savarirayan
Melita Irving
Carlos A. Bacino
Julie Hoover-Fong
Keiichi Ozono
Klaus Mohnike
William R. Wilcox
Michael B. Bober
Joshua Henshaw
Publication date: 23-04-2024
Publisher: Springer International Publishing
Keywords: Achondroplasia
Pharmacokinetics
Published in: Clinical Pharmacokinetics / Issue 5/2024
Print ISSN: 0312-5963
Electronic ISSN: 1179-1926
DOI: https://doi.org/10.1007/s40262-024-01371-6

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Development of a Weight-Band Dosing Approach for Vosoritide in Children with Achondroplasia Using a Population Pharmacokinetic Model

Abstract

Background and Objective

Methods

Results

Conclusions

Clinical Trial Registration

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background and Objective

Methods

Results

Conclusions

Clinical Trial Registration

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