Bone growth drug benefits children with dwarfism

A drug that boosts bone growth in children with achondroplasia — the most common form of dwarfism — may also reduce their chances of sudden infant death syndrome (SIDS), sleep apnoea and needing surgery, according to an international study.

Achondroplasia, a genetic bone disorder affecting one in every 25,000 children, is caused by a mutation in the FGFR3 gene. The condition slows bone growth in children’s limbs and spines and narrows the base of the skull, putting pressure on the spinal cord. Patients under the age of five are 50 times more likely to die due to complications of this narrowing, which causes spinal cord compression and breathing difficulties.

Researchers at the Murdoch Children’s Research Institute (MCRI), led by Professor Ravi Savarirayan, have previously shown that the drug vosoritide improves bone growth development in achondroplasia patients aged from 5–18 years. This latest study, funded by vosoritide manufacturer Biomarin Pharmaceutical, found the drug produced similar results in children and infants as young as four months.

The randomised controlled trial involved 75 children under five from Australia, US, Japan and the UK, who underwent 52 weeks of vosoritide treatment. The study found the drug increased height, facial volume and the size of the foramen magnum — the hole at the base of the skull that connects the brain with the spinal cord — which was particularly increased in children aged six months and under.

Savarirayan said the findings, which were published in The Lancet Child & Adolescent Health, will not only vastly improve quality of life but could ultimately save lives, with no serious side effects reported.

“The management of achondroplasia is evolving from purely treating the symptoms to identifying drugs that improve skeletal growth,” he said. Improved growth may also reduce the need for facial surgery and corrective orthodontic treatments, which are often required later in life.

The study found the annual growth rate was 0.78 cm in treated children under five, compared with 1.57 cm in those five years and older who undertook previous clinical trials. According to Savarirayan, “The smaller height rise could be because in very young children with achondroplasia, there is rapidly declining growth, where a small difference in age can have a big impact on growth measurements. This height deficit accumulates rapidly up to the age of two and then follows a more gradual decline.”

Earlier this year, the Australian Government listed vosoritide on the PBS for treatment of achondroplasia, making it the first and only approved medicine on the PBS that targets the underlying cause of the condition. The eligible age to first access vosoritide therapy for achondroplasia varies between countries; the US recently dropped the age from five to birth, based on the results of this study. In Australia the drug is listed on the PBS from birth.

“The study findings will be crucial when relevant authorities are deciding whether to lower the age from which vosoritide can be taken with the first few months of life; the time where we expect to see the greatest potential medical benefits,” Savarirayan said. “It will also be of considerable use to paediatricians and other healthcare specialists who are assessing the risks and benefits of starting vosoritide treatment in young children with achondroplasia.”

Image caption: Before and after — four-year-old Casper’s parents have observed some remarkable changes since enrolling him in the vosoritide trial when he was just five months old.