BACKGROUND: X-linked hypophosphatemia is characterized by increased secretion of 
fibroblast growth factor 23 (FGF-23), which leads to hypophosphatemia and 
consequently rickets, osteomalacia, and skeletal deformities. We investigated 
burosumab, a monoclonal antibody that targets FGF-23, in patients with X-linked 
hypophosphatemia.
METHODS: In an open-label, phase 2 trial, we randomly assigned 52 children with 
X-linked hypophosphatemia, in a 1:1 ratio, to receive subcutaneous burosumab 
either every 2 weeks or every 4 weeks; the dose was adjusted to achieve a serum 
phosphorus level at the low end of the normal range. The primary end point was 
the change from baseline to weeks 40 and 64 in the Thacher rickets severity 
total score (ranging from 0 to 10, with higher scores indicating greater disease 
severity). In addition, the Radiographic Global Impression of Change was used to 
evaluate rachitic changes from baseline to week 40 and to week 64. Additional 
end points were changes in pharmacodynamic markers, linear growth, physical 
ability, and patient-reported outcomes and the incidence of adverse events.
RESULTS: The mean Thacher rickets severity total score decreased from 1.9 at 
baseline to 0.8 at week 40 with every-2-week dosing and from 1.7 at baseline to 
1.1 at week 40 with every-4-week dosing (P<0.001 for both comparisons); these 
improvements persisted at week 64. The mean serum phosphorus level increased 
after the first dose in both groups, and more than half the patients in both 
groups had levels within the normal range (3.2 to 6.1 mg per deciliter [1.0 to 
2.0 mmol per liter]) by week 6. Stable serum phosphorus levels were maintained 
through week 64 with every-2-week dosing. Renal tubular phosphate reabsorption 
increased from baseline in both groups, with an overall mean increase of 0.98 mg 
per deciliter (0.32 mmol per liter). The mean dose of burosumab at week 40 was 
0.98 mg per kilogram of body weight with every-2-week dosing and 1.50 mg per 
kilogram with every-4-week dosing. Across both groups, the mean serum alkaline 
phosphatase level decreased from 459 U per liter at baseline to 369 U per liter 
at week 64. The mean standing-height z score increased in both groups, with 
greater improvement seen at all time points with every-2-week dosing (an 
increase from baseline of 0.19 at week 64) than with every-4-week dosing (an 
increase from baseline of 0.12 at week 64). Physical ability improved and pain 
decreased. Nearly all the adverse events were mild or moderate in severity.
CONCLUSIONS: In children with X-linked hypophosphatemia, treatment with 
burosumab improved renal tubular phosphate reabsorption, serum phosphorus 
levels, linear growth, and physical function and reduced pain and the severity 
of rickets. (Funded by Ultragenyx Pharmaceutical and Kyowa Hakko Kirin; 
ClinicalTrials.gov number, NCT02163577 ; EudraCT number, 2014-000406-35 ).