Key takeaways:
- Growth velocity and standing height standard deviation scores increased at 1 year for children with hypochondroplasia receiving vosoritide.
- No treatment-related serious adverse events were reported.
Children with hypochondroplasia had an increase in growth velocity at 1 year of treatment with vosoritide, according to findings from a phase 2 trial.
As Healio previously reported, the FDA issued an expanded indication for vosoritide (Voxzogo, BioMarin Pharmaceutical) to include children of all ages with achondroplasia with open epiphyses. In new findings published in eClinicalMedicine, researchers assessed the safety and efficacy of vosoritide among children with hypochondroplasia, a rare autosomal dominant skeletal dysplasia that is associated with short stature.
Data were derived from Dauber A, et al. eClinicalMedicine. 2024;doi:10.1016/j.eclinm.2024.102591.
“Vosoritide was recently approved for treatment of children with achondroplasia,” Andrew Dauber, MD, MMSc, chief of endocrinology at Children’s National Hospital in Washington, D.C., told Healio. “Our current study suggests that it could be equally efficacious (if not even slightly more efficacious) in children with hypochondroplasia as well. If this increase in growth velocity is sustained over time, it could lead to a meaningful increase in adult height for individuals with hypochondroplasia.”
Dauber and colleagues conducted a phase 2, open-label trial enrolling 24 prepubertal children aged 3 to 10 years for boys and 3 to 9 years for girls who had a confirmed mutation in the FGFR3 gene that is associated with hypochondroplasia. Children who had a standing height standard deviation (SD) score of –2.25 or less for their sex and age on CDC growth charts and did not have growth hormone deficiency were eligible for the trial (mean age, 5.9 years; 50% girls).
“While hypochondroplasia is a rare disease, children and adults with this condition can have significant short stature, which impacts their daily life,” Dauber said. “They are highly motivated to have a therapy [that] can help them grow better. It is imperative that the medical field help these patients by developing medications targeted to rare diseases.”
Baseline annualized growth velocity was determined during a 6-month observation period. After the observation period, participants received once-daily 15 µg/kg vosoritide for 1 year. Study visits took place every 6 months with frequent telephone contact between visits to assess treatment adherence and adverse events. The study’s primary outcomes were safety and tolerability of vosoritide, change in annualized growth velocity from baseline to 12 months and change in height SD score from baseline to 12 months.
Annualized growth velocity increased from a mean 5.12 cm per year at baseline to 6.93 cm per year at 1 year of vosoritide (P < .0001). The increase in growth velocity was observed from baseline to 6 months and sustained from 6 months to 1 year. Standing height SD scores increased by a mean of 0.01 SD at baseline to 0.37 SD at 1 year (P < .0001).
In secondary post hoc analysis, increases in growth velocity were observed for all children except for three participants aged 9 to 10 years. No increase in growth velocity was observed for those with a baseline growth velocity of 5 cm per year or higher at baseline.
No treatment-related serious adverse events were observed with vosoritide. Injection site reactions were reported at least once by 83.3% of participants. There were no episodes of symptomatic hypotension. The researchers said no new safety concerns were found compared with previously publishes studies of vosoritide among children with achondroplasia.
The phase 2 trial is part of a group of trials assessing vosoritide for children with genetic causes of short stature. Future trials will enroll children with Noonan syndrome, those with mutations in aggrecan and NPR2 genes and girls with Turner syndrome. Dauber said a phase 3 trial is also being planned for children with hypochondroplasia.
For more information:
Andrew Dauber, MD, MMSc, can be reached at adauber@childrensnational.org.
Sources/Disclosures
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Disclosures:
Dauber reports serving as a consultant for BioMarin with all compensation being paid to his institution and receiving an investigator-initiated grant from BioMarin to conduct the study. Please see the study for all other authors’ relevant financial disclosures.