Daily vosoritide increases annual growth velocity in children with achondroplasia
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Children with achondroplasia assigned a daily dose of vosoritide for 1 year experienced a larger increase in annual growth velocity than children assigned placebo, according to a speaker.
“To our knowledge, this is the first targeted therapy for achondroplasia that has resulted in a highly significant increase in annualized growth velocity and change in height z score compared to placebo in children with achondroplasia,” Lynda Polgreen, MD, MS, investigator and associate professor of pediatrics, The Lundquist Institute at Harbor-UCLA Medical Center, David Geffen School of Medicine, told Healio.
Polgreen presented the findings at the American Society for Bone and Mineral Research virtual meeting.
Vosoritide (BioMarin Pharmaceutical) is an investigational, once-daily injection analogue of C-type natriuretic peptide for the treatment of achondroplasia, the most common cause of dwarfism. The therapy has orphan drug status in the U.S. and Europe.
Polgreen and colleagues conducted a randomized, phase 3, double-blind trial with children aged at least 5 years with achondroplasia at 24 hospitals in seven countries. All participants previously spent at least 6 months in an observational study for baseline growth measurements. Researchers randomly assigned children once-daily subcutaneous vosoritide (15 mg per 1 kg of body weight; n = 60) or placebo (n = 61). Both groups were balanced by sex and Tanner stage. Researchers recorded the change in annualized growth velocity at 52 weeks, change in height z score and change in upper-to-lower body segment ratio.
At baseline, the vosoritide and placebo groups had similar mean growth velocity, height z score, body segment ratio and standing height. At 52 weeks, children assigned vosoritide (n = 58) had a higher mean annualized growth velocity of 1.57 cm compared with children assigned placebo (95% CI, 1.22-1.93). Additionally, the vosoritide group had an increase in serum collagen X, a marker for endochondral bone formation, from 13 weeks after treatment through the end of the 52-week period.
The vosoritide group also had a larger increase in height z score vs. placebo (mean increase, 0.28; 95% CI, 0.17-0.39).
The vosoritide group had a larger number of total adverse events due to injection site reactions, but there was minimal difference in the number of grade three or higher adverse events or severe adverse events between groups, Polgreen said. None of the severe events were related to vosoritide.
“These data are consistent with those observed in the phase 2 trials of vosoritide that have been previously published,” Polgreen said during the presentation. “Participants continue treatment with vosoritide in the extension study, where long-term effects of treatment can be evaluated until final adult height.”
In addition to the extension study, a phase 2, double-blind, randomized controlled trial is also underway for children aged 5 years or younger with achondroplasia. Polgreen said both studies could help answer questions about whether vosoritide can prevent or treat nongrowth medical complications of achondroplasia and provide long-term safety and efficacy data.
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Savarirayan R, et al. A randomized controlled trial of vosoritide in children with achondroplasia. Presented at: American Society for Bone and Mineral Research Annual Meeting; Sept. 11-15, 2020 (virtual meeting).
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