medwireNews: Burosumab treatment improves rickets and prevents decline in growth in young children with X-linked hypophosphataemia, show the findings of an open-label phase II study.
The treatment is a monoclonal antibody against circulating phosphatonin fibroblast growth factor 23, high levels of which cause renal phosphate wasting and hypophosphataemia, rickets, skeletal deformities and growth impairment in children with X-linked hypophosphataemia.
Burosumab also had a good safety profile, report Michael Whyte (Shriners Hospital for Children, St Louis, Missouri, USA) and co-researchers.
There were just 14 adverse events thought to be related to burosumab, during 64 weeks of its use in 13 children, of which most were injection site reactions and all were mild, the team reports in The Lancet Diabetes & Endocrinology.
The patients received subcutaneous burosumab 0.8 mg/kg once every 2 weeks. In an accompanying editorial, John Pettifor (University of the Witwatersrand, Johannesburg, South Africa) notes that conventional therapy with vitamin D and oral phosphate supplements has to be taken up to five times daily, “making long-term compliance a problem, especially in school-aged children.”
All children (69% boys) in the trial had been receiving conventional therapy for an average of 16 months, yet they still experienced significant improvements in their condition after switching to burosumab, at an average age of 2.9 years.
After dose increases in three patients, burosumab treatment raised fasting serum phosphorus levels to within the normal range, at a 40-week average of 1.12 mmol/L from a baseline of 0.31 mmol/L, with no instances of hyperphosphataemia.
Thacher Rickets Severity Score fell from a baseline average of 2.9 to a 40-week average of 1.2, and this was associated with a significant improvement in Radiographic Global Impression of Change score, by 2.3 points, with all patients achieving at least a 2.0-point improvement, which was the researchers’ definition of substantial healing.
In untreated historical controls with X-linked hypophosphataemia, patients experienced a progressive decline in their length/height standard deviation scores (SDSs) from around the age of 1 year (ie, when they learned to walk).
The patients in the current study had a reduced average length/height SDS at baseline, at –1.38, and this declined only slightly and nonsignificantly during treatment, to –1.64 after 64 weeks, with patients’ growth generally following the normal population growth curves.
However, in his editorial, Pettifor notes that there was no sign of catch-up growth, and that more research is therefore needed to determine if age at initiation of burosumab treatment “influences growth responses and final mature height.”
He says: “It is a pity that the study was not done as a randomised controlled trial, using affected children on conventional therapy as the control, because the information obtained would have helped to determine the effect of burosumab on growth rates and on radiological healing, both of which are important outcomes for any new proposed therapy.”
Pettifor adds that questions remain around the completeness of bone response, given that “changes suggestive of rickets were still present at the wrist or knee at the end of the study”, and the duration of treatment, added to which is the problem that the cost of the medication may make it affordable only in high-income countries.
By Eleanor McDermid
medwireNews is an independent medical news service provided by Springer Healthcare. © 2019 Springer Healthcare part of the Springer Nature group
Lancet Diabetes Endocrinol 2019; doi:10.1016/S2213-8587(18)30338-3
Lancet Diabetes Endocrinol 2019; doi:10.1016/S2213-8587(19)30004-X