Prolonged Correction of Serum Phosphorus in Adults With X-Linked Hypophosphatemia Using Monthly Doses of KRN23

Context: In X-linked hypophosphatemia (XLH), elevated fibroblast growth factor 23 (FGF23) decreases the renal tubular maximum reabsorption rate of phosphate/glomerular filtration rate (TmP/GFR) and serum inorganic phosphorus (Pi), resulting in rickets and/or osteomalacia. Objective: The objective was to test the hypothesis that monthly KRN23 (anti-FGF23 antibody) would safely improve serum Pi in adults with XLH. Design: Two sequential open-label phase 1/2 studies were done. Setting: Six academic medical centers were used. Participants: Twenty-eight adults with XLH participated in a 4-month dose-escalation study (0.05–0.6 mg/kg); 22 entered a 12-month extension study (0.1–1 mg/kg). Intervention: KRN23 was injected sc every 28 days. Main Outcome Measure: The main outcome measure was the proportion of subjects attaining normal serum Pi and safety. Results: At baseline, mean TmP/GFR, serum Pi, and 1,25-dihydroxyvitamin D [1,25(OH)2D] were 1.6 ± 0.4 mg/dL, 1.9 ± 0.3 mg/dL, and 36.6 ± 14.3 pg/mL, respectively. ...