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Vosoritide treatment for children with hypochondroplasia: a phase 2 trial
Andrew Dauber1,2, Anqing Zhang3, Roopa Kanakatti Shankar1,2
1Division of Endocrinology, Children's National Hospital, Washington, DC 20010, USA.
Insights
Vosoritide effectively increased growth velocity in children with hypochondroplasia, a rare skeletal dysplasia. This C-type natriuretic peptide analog demonstrated safety and efficacy comparable to its use in achondroplasia.
Area of Science:
- Pediatric Endocrinology
- Skeletal Dysplasias
- Pharmacology
Background:
- Hypochondroplasia is a rare autosomal dominant skeletal dysplasia caused by FGFR3 variants, leading to disproportionate short stature.
- Current treatments for short stature in children with hypochondroplasia are lacking.
- Vosoritide, a C-type natriuretic peptide analog, is approved for achondroplasia growth improvement.
Purpose of the Study:
- To evaluate the safety and efficacy of vosoritide in children diagnosed with hypochondroplasia.
- To assess the impact of vosoritide on growth velocity and height standardized deviation score (SDS).
Main Methods:
- A single-arm, phase 2, open-label trial involving 26 children with hypochondroplasia.
- A 6-month observation period followed by a 12-month intervention with daily subcutaneous vosoritide (15 μg/kg/day).
- Co-primary endpoints included adverse events, change in annualized growth velocity, and height SDS.
Main Results:
- Twenty-four participants received vosoritide; it was well-tolerated with no serious adverse events.
- Annualized growth velocity increased by 2.26 SD, and height SDS increased by 0.36 SD.
- Absolute annualized growth velocity increased by 1.81 cm/year, with a 0.38 SD increase in hypochondroplasia-specific height SDS.
Conclusions:
- Vosoritide is a safe and effective treatment for increasing growth velocity in children with hypochondroplasia.
- The efficacy observed in hypochondroplasia is similar to that reported in achondroplasia patients.
Background:
Hypochondroplasia is a rare autosomal dominant skeletal dysplasia due to activating variants in FGFR3. It presents with disproportionate short stature with a wide range of clinical severity. There are currently no approved medications to treat short stature in children with hypochondroplasia. Vosoritide is a C-type natriuretic peptide analog that was recently approved for improving growth in children with achondroplasia. We aimed to evaluate the safety and efficacy of vosoritide in children with hypochondroplasia.
Methods:
We conducted a single-arm, phase 2, open-label trial at a single centre in the USA and enrolled 26 children with hypochondroplasia. The trial consists of a 6-month observation period to establish a baseline annualized growth velocity followed by a 12-month intervention period during which vosoritide is administered daily via subcutaneous injection at a dose of 15 μg/kg/day. The trial's co-primary endpoints included the incidence of adverse events and the change from baseline in age-sex standardized annualized growth velocity and height standardized deviation score (SDS) after 12 months of treatment. This trial is registered with ClinicalTrials.gov (NCT04219007).
Findings:
Twenty-four participants with a mean age of 5.86 years received vosoritide therapy. The first participant was enrolled on August 4, 2020, and the final participant completed the 18-month trial on September 8, 2023. Vosoritide was well tolerated with no treatment-related serious adverse events. Injection site reactions occurred in 83.3% of participants. No participants discontinued therapy due to an adverse event. Annualized growth velocity increased by 2.26 standard deviations (SD) and height SDS increased by 0.36 SD during the treatment period versus the observation period. Hypochondroplasia specific height SDS increased by 0.38 SD. There was a 1.81 cm/year increase in absolute annualized growth velocity.
Interpretation:
Vosoritide was safe and effective in increasing growth velocity in children with hypochondroplasia. Efficacy was similar to what has been reported in children with achondroplasia.
Funding:
This study was supported by an investigator-initiated grant from BioMarin Pharmaceutical.
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