In X-linked hypophosphatemia (XLH), inherited loss-of-function mutations in the 
PHEX gene cause excess circulating levels of fibroblast growth factor 23 
(FGF23), leading to lifelong renal phosphate wasting and hypophosphatemia. 
Adults with XLH present with chronic musculoskeletal pain and stiffness, short 
stature, lower limb deformities, fractures, and pseudofractures due to 
osteomalacia, accelerated osteoarthritis, dental abscesses, and enthesopathy. 
Burosumab, a fully human monoclonal antibody, binds and inhibits FGF23 to 
correct hypophosphatemia. This report summarizes results from a double-blind, 
placebo-controlled, phase 3 trial of burosumab in symptomatic adults with XLH. 
Participants with hypophosphatemia and pain were assigned 1:1 to burosumab 
1 mg/kg (n = 68) or placebo (n = 66) subcutaneously every 4 weeks (Q4W) and were 
comparable at baseline. Across midpoints of dosing intervals, 94.1% of 
burosumab-treated participants attained mean serum phosphate concentration above 
the lower limit of normal compared with 7.6% of those receiving placebo (p < 
0.001). Burosumab significantly reduced the Western Ontario and the McMaster 
Universities Osteoarthritis Index (WOMAC) stiffness subscale compared with 
placebo (least squares [LS] mean ± standard error [SE] difference, -8.1 ± 3.24; 
p = 0.012). Reductions in WOMAC physical function subscale (-4.9 ± 2.48; 
p = 0.048) and Brief Pain Inventory worst pain (-0.5 ± 0.28; p = 0.092) did not 
achieve statistical significance after Hochberg multiplicity adjustment. At week 
24, 43.1% (burosumab) and 7.7% (placebo) of baseline active fractures were fully 
healed; the odds of healed fracture in the burosumab group was 16.8-fold greater 
than that in the placebo group (p < 0.001). Biochemical markers of bone 
formation and resorption increased significantly from baseline with burosumab 
treatment compared with placebo. The safety profile of burosumab was similar to 
placebo. There were no treatment-related serious adverse events or meaningful 
changes from baseline in serum or urine calcium, intact parathyroid hormone, or 
nephrocalcinosis. These data support the conclusion that burosumab is a novel 
therapeutic addressing an important medical need in adults with XLH.© 2018 The 
Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, 
Inc.