An Australian-led phase 3 trial has confirmed that a novel drug vosoritide may be the first effective medication for improving bone growth in children with achondroplasia, the most common form of dwarfism.
Children who took the C-type natriuretic peptide analogue for 12 months showed an average annualised growth velocity increase of 1.57cm compared to those who took placebo, according to Melbourne clinical geneticist Professor Ravi Savarirayan, lead investigator of the international multicentre study.
The one year randomised controlled trial that was conducted in 24 centres across seven countries and involved 121 children aged between five and 18 years of age with a clinical diagnosis of achondroplasia.
Achondroplasia is a genetic bone disorder affecting about one in every 25,000 children. It is caused by overactivity of the FGFR3 protein, which slows bone growth. Currently the only treatment offered in Australia is surgery, which is often not successful. Vosoritide blocks the activity of FGFR3, returning growth rates to normal.
Children were randomised to daily subcutaneous injections of vosoritide (n=60) or placebo (n=61) for 52 weeks.
Results published in The Lancet showed that for the primary endpoint of change from baseline in mean growth velocity at 52 weeks the difference was 1·57 cm/year in favour of vosoritide (95% CI [1·22–1·93]; two-sided p<0·0001).
The drug also appeared to be well tolerated with a similar rate of adverse events to the placebo group, and no serious adverse events that were considered to be treatment related.
However the study authors cautioned that it is not known whether final adult height will be increased, or what the harms of long-term therapy might be.
Professor Savarirayan, Group leader of Musculoskeletal Research at the Murdoch Children’s Research Institute and the Victorian Clinical Genetic Services, said the growth velocity seen in the study was similar to that seen in other children.
“This is the first really robust gold standard evidence that this medication is both safe and effective,” he said.
“This means that children [with achondroplasia] can grow like their normal counterparts, but in addition we hope the complications of the spine and compression of various nerves, bowing of the legs and problems with sleeping will be alleviated by this extra growth in bones – because it doesn’t just cause growth of the long bones but it increases growth of the spine.”
Professor Savarirayan said the restoration of bone growth by injections given in the home setting would allow children with the condition to have increased independence, increased functionality in their life and to avoid hospital visits.
“Anecdotally, our patients tell us they now are able to do more stuff like climbing trees, jumping rocks and being more independent generally, which is specific to their experiences.”
He said the trial had created the groundwork for regulatory approval of the drug in the US, Europe and hopefully Australia.
Manufacturer and trial sponsor BioMarin recently announced that authorisation by the European Medicines Agency and has also submitted a New Drug Application to the U.S. Food and Drug Administration (FDA) for vosoritide.
Professor Savarirayan declared he had no financial interests in BioMarin but had received consulting fees and grants from the company.