Vosoritide shows promise for treatment of hypochondroplasia

medwireNews: Vosoritide treatment appears to increase growth velocity in children with hypochondroplasia and is well tolerated, show study findings.

“Efficacy was similar to what has been reported in children with achondroplasia”, note the researchers Andrew Dauber and colleagues from the Children’s National Hospital in Washington, DC, USA.

They continue in eClinicalMedicine: “This study supports the development of vosoritide and potentially other [C-type natriuretic peptide] based therapies for children with hypochondroplasia.”

The phase 2, open-label trial involved 24 children (50% boys) with a mean age of 5.86 years (no older than 10 years for boys and 9 years for girls) who were prepubertal, had a confirmed mutation in the FGFR3 gene associated with hypochondroplasia and did not have growth hormone deficiency. The children had a mean baseline standing height of –3.29 standard deviation score (SDS).

Following a 6-month observation period during which the mean baseline annualised growth velocity was determined, the participants received a daily subcutaneous injection of vosoritide 15 µg/kg for 12 months.

“Adherence to daily vosoritide administration was excellent,” the team remarks, with a mean administration rate of 98.7%. None of the participants discontinued therapy; one patient suspended treatment following purpura and petechiae later determined to be grade 4 post-viral immune thrombocytopenia.

Overall, the safety profile was “reassuring,” say Dauber et al. There were “no new significant safety concerns” and no treatment-related serious adverse events. Injection site reactions occurred in 83.3% of children, all of which were of grade 1 or 2 and resolved without intervention.

With regard to efficacy, the children’s absolute annualised growth velocity increased significantly from a mean 5.12 cm/year during the observation period to 6.93 cm/year after 12 months of treatment, giving a mean difference of 1.81 cm/year.

This corresponded to a mean 2.26 SDS increase in age- and sex-adjusted standardised annualised growth velocity, from a mean –1.14 SDS during the observation period to 1.12 SDS after the 12 months of treatment.

The researchers found that the increase in growth velocity occurred during the first 6 months of treatments and was then sustained. “It is important to note that growth velocity normally decreases in children in this younger age group, so maintaining a stable growth velocity represents a positive outcome in this group,” the team points out.

In post-hoc analyses looking at annualised growth velocity SDS according to age, the difference between the observation and treatment periods was significant for children aged 3–4 years and 5–8 years but not significant for those aged 9–10 years, with respective mean differences of 2.05, 3.21 and –0.55 cm/year.

An increase in growth rate occurred irrespective of baseline height SD score, but Dauber et al note that it “was only significant in those with baseline [annualized growth velocity] less than or equal to 5 cm/year.” They say: “It is unclear if this is due to a maximal achievable growth velocity in children with hypochondroplasia.”

The age- and sex-adjusted standardised height also increased significantly with treatment, from a mean –3.29 SDS at baseline to –2.91 SDS, a 0.36 SDS difference based on US CDC growth charts. The results were similar when hypochondroplasia-specific growth charts were used, with a mean increase of 0.38 SDS, from –0.41 to 0.03 SDS.

The study authors believe that the “increases in height may lead to long-term gains in final adult height,” on finding that the secondary outcome of ratio of bone age to chronological age did not increase with vosoritide treatment, “although additional studies are needed to verify this conclusion.”

They conclude that “1 year of daily administration of vosoritide results in improved growth in children with hypochondroplasia with a relatively benign side effect profile,” adding that “[a]dditional studies are needed to see the long-term effects of vosoritide in children with hypochondroplasia.”

By Lucy Piper

medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2024 Springer Healthcare Ltd, part of the Springer Nature Group

eClin Med 2024; doi:10.1016/j.eclinm.2024.102591
Martin Savage
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