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 (0.050.6 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)(2)D] were 1.6 +/- 0.4 mg/dL, 1.9 +/- 0.3 mg/dL, and 36.6 +/- 14.3 pg/mL, respectively. During dose escalation, TmP/GFR, Pi, and 1,25(OH)(2)D increased, peaking at 7 days for TmP/GFR and Pi and at 3-7 days for 1,25(OH)(2)D, remaining above (TmP/GFR, Pi) or near [1,25(OH)(2)D] pre-dose levels at trough. After each of the four escalating doses, peak Pi was between 2.5 and 4.5 mg/dL in 14.8, 37.0, 74.1, and 88.5% of subjects, respectively. During the 12-month extension, peak Pi was in the normal range for 57.9-85.0% of subjects, and >25% maintained trough Pi levels within the normal range. Serum Pi did not exceed 4.5 mg/dL in any subject. Although 1,25(OH)(2)D levels increased transiently, mean serum and urinary calcium remained normal. KRN23 treatment increased biomarkers of skeletal turnover and had a favorable safety profile. Conclusions: Monthly KRN23 significantly increased serum Pi, TmP/GFR, and 1,25(OH)(2)D in all subjects. KRN23has potential for effectively treating XLH.