Burosumab in Chinese adults with X-linked hypophosphatemia: a phase 4 study

X-linked hypophosphatemia (XLH) is a rare genetic disorder, for which burosumab treatment may be beneficial. This study evaluated the efficacy, pharmacokinetics, and safety of burosumab in Chinese adults with XLH. In this open-label, multicenter, post-marketing phase 4 study, 18 Chinese adult outpatients with XLH received conventional oral phosphate (30 mg/kg/d in 5 doses) and calcitriol (0.50 μg/d in 2 doses) during a 14-wk run-in period. Patients then received subcutaneous burosumab 1.0 mg/kg every 4 wk for 48 wk (12 doses). The main outcome measures were changes from baseline in mean serum phosphate level at the end of burosumab treatment, along with patient-reported outcomes. Sixteen (88.9%) and four (22.2%) patients achieved mean serum phosphate levels >2.5 mg/dL at the mid-point and the end of the dose cycle, respectively. The mean (SD) serum phosphate level increased from 1.6 (0.25) mg/dL at baseline to 2.4 (0.28) mg/dL at the end of the dose cycle. The mean (SD) change from baseline in serum phosphate level was 50.1% (14.11%) following burosumab treatment. The tubular maximum reabsorption rate of phosphate to glomerular filtration rate (TmP/GFR) increased from 1.3 (0.32) mg/dL at Wk 0 to 2.0 (0.42) mg/dL at Wk 48. Over 48 wk, patients reported that their worst pain, severity, interference, and stiffness were relieved and Measurement Information System quality of life assessment scores increased. Motor function assessed by the 6-min walking test improved significantly, (72.7% increase from baseline to Wk 48). All treatment-emergent adverse events were mild or moderate; none were serious or serious treatment-related. Burosumab treatment led to sustained correction of serum phosphate levels, enhanced renal phosphate reabsorption (ie, TmP/GFR improvements), and improved stiffness, pain, and functional exercise capacity. Treatment was well-tolerated without any new safety signals in Chinese patients with XLH.