Burosumab Heals Rickets in Children With X-Linked Hypophosphataemia

April 11, 2019

By Jill Stein

PARIS -- April 9, 2019 -- Children with X-linked hypophosphataemia (XLH) experience larger improvements in rickets and other outcomes when treated with the investigational agent burosumab than with conventional treatment, according to a study presented here at the 2019 World Congress on Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (WCO).

For the open-label, phase 3 study, Wolfgang Högler, MD, Johannes Kepler University Linz, Linz, Austria, and colleagues randomised 61 children (aged 1 to 12 years) 1:1 to receive burosumab starting at 0.8 mg/kg administered subcutaneously every 2 weeks for 64 weeks or to reinitiate standard treatment with oral phosphate salts and active vitamin D metabolites (Pi/D) titrated by the researchers for the same period of time.

The burosumab dose was increased if 2 consecutive pre-dose, fasting serum concentrations were

At week 40, a significantly higher percentage of children taking burosumab achieved substantial healing of rickets (Radiographic Global Impression of Change [RGI-C] ≥+2.0) compared with children taking Pi/D (72% vs 6%). At week 64, these percentages increased to 87% and 17%, respectively.

Burosumab was also associated with larger improvements in leg deformities, height, and distance walked in a 6-minute test along with larger increases in serum phosphorus and active vitamin D levels.

The researchers reported no concerning safety findings throughout the 64 weeks of burosumab treatment.

At baseline, the patients had a total Rickets Severity Score (RSS) of ≥2.0, despite prior Pi/D treatment. Prior to randomisation, the patients underwent a 7-day washout from Pi/D.

Radiologists blinded to treatment assessed rickets healing using the RGI-C at week 40. The RGI-C is a 7-point scale describing x-ray changes at the wrist, knee, and leg during treatment.

XLH is a lifelong, sometimes debilitating, and deformative bone disease mediated by high levels of circulating fibroblast growth factor-23. XLH-associated skeletal abnormalities, including rickets with bowing of the legs, can significantly impair gross motor function and quality of life during childhood, and can cause impairments lasting into adulthood. The disease affects approximately 3,000 children and 12,000 adults in the United States.

Burosumab is a fully human monoclonal antibody that inhibits the function of fibroblast growth factor-23. In 2 prior phase 2 studies, burosumab was associated with improvements in rickets and serum phosphorus in children with XLH aged 1 to 12 years, as well as improvement in growth and physical function in children with XLH aged 5 to 12 years.

Funding for this study was provided by Ultragenyx Pharmaceutical Inc., Novato, California.

[Presentation title: Burosumab Resulted in Greater Improvement in Phosphate Metabolism, Rickets, Growth, and Mobility Than Continuation With Conventional Therapy in Children With X-Linked Hypophosphataemia (XLH). Abstract P428]