Precision medicine improves growth for children with a rare form of rickets

A new, targeted drug has been shown to significantly improve growth and control of rickets in children with X-linked hypophosphataemic rickets (XLH), a serious condition affecting about 300 children in the UK.

XLH is caused by genetic mutation that leads to excess activity of fibroblast growth factor (FGF23) which causes the kidneys to leak too much phosphate. Symptoms include joint pains, weaker bones, bowing of the legs and impaired growth.

In the international study, 52 children aged 5-12 years old, including three patients from Great Ormond Street Hospital (GOSH), were treated every two or four weeks with burosomab, an antibody to FGF23 that reduces phosphate losses in the urine. Burosumab inhibited FGF23 and restored phosphate levels. After 64 weeks of treatment with burosumab, patients reported less pain and joint X-rays showed a 50% reduction in disease severity and significantly improved growth rates.

“This is a very exciting development for children with XLH as this is the first drug to act directly on the cause of the condition and the study showed that it led to major improvements in children who were considered well-treated with the standard drugs - phosphate supplements and activated vitamin D". said Dr William van’t Hoff, trial lead at GOSH and Director of the NIHR GOSH Clinical Research Facility (CRF) where trial participants were cared for.

"Children tolerated the fortnightly injections, no child in the trial stopped and all have opted to continue with burosumab”, added Dr van't Hoff.

Following publication of interim results in December 2017, burosumab has received a positive European Commission decision granting a conditional marketing authorisation and has received FDA approval. The results were recently published in the New England Journal of Medicine and an extension study is now ongoing to further investigate the long-term effects of the drug.

This research is just one example of how precision medicine is helping develop targeted treatments for children with complex health conditions.The drug holds promise for improving long-term outcomes for children with XLH and represents an important advance for the patients and their families.

The study was carried out in partnership with Ultragenyx pharmaceuticals and colleagues in the US, the Netherlands and France as well as the NIHR CRFs in Manchester and Birmingham.