A biologic analogue of C-type natriuretic peptide is showing promise as a therapy to improve bone growth in children with achondroplasia.
An international phase 2 dose-finding and extension study, led by Melbourne clinical geneticist Professor Ravi Savarirayan, has found daily subcutaneous injections of vosoritide were well tolerated in the children.
The study of 35 children aged 5-14 years treated participants according to four dose regimens – either escalating doses from 2.5 to 7 then 15 µg/kg, 7.5 to 15µg/kg or stable dosing at 15 or 30µg/kg.
While the primary outcome measures were related to safety, the secondary outcome of annualised growth velocity increased with treatment compared to baseline.
Dose dependent increases in height z scores were observed up to 15µg/kg and sustained for 42 months.
The study found adverse events included transient and minor injection site reactions, pyrexia, cough and hypotension.
Serious adverse events occurred in just 4 of the 35 children (11%) and included grade 3 obstructive sleep apnoea, grade 1 tonsillar hypertrophy, grade 3 thyroglossal cysts and grade 3 syrinx thought not to be related to the medication.
No deaths occurred and there were no adverse events related to disproportionate skeletal growth or clinically significant cardiovascular effects.
“No difference in efficacy or safety could be identified between the once-daily doses of 15.0 and 30.0 µg/kg; thus, our findings support the choice of the lower dose for further evaluation in ongoing studies,” the study said.
Professor Savarirayan, from the Murdoch Children’s Research Institute and the Victorian Clinical Genetic Services, told the limbic achondroplasia was not just about height, but about health.
“These children have an increased risk of pressure on the brain needing an operation in the first year of life, there is an increased risk of neurosurgery to the top of the spine, and in the first five years of life there is a 40-times increased risk of sudden infant death syndrome so there is clearly an unmet need for treatments.”
“The only things we do at the moment are surgical treatments, a lot of which are unsuccessful.”
He said a phase 3 randomised controlled trial of vosoritide was due to finish recruiting in October. It would provide more information on the drug’s long- term impact on morbidity and mortality.
“All of the children in the trial will be followed to final adult height – so for boys, potentially 20 years, and for girls, 18 years – so we are going to get some really good robust data on the frequency of operations in the treated versus the untreated groups.”
Professor Savarirayan said vosoritide wasn’t a cure for achondroplasia but would provide families with an option.
“Achondroplasia affects every bone in the body not just the long bones so we’re hoping to affect the size of the foramen magnum where patients often need neurosurgery and also the spinal canal so they don’t need more surgery on their spine which about 50% will need by about age 30.”
A phase 2 randomised controlled trial for infants is also underway.