• Erik A Imel, Xiaoping Zhang, Mary D Ruppe, Thomas J Weber, Mark A Klausner, Takahiro Ito, Maria Vergeire, Jeffrey S Humphrey, Francis H Glorieux, Anthony A Portale, Karl Insogna, Munro Peacock, and Thomas O Carpenter.
• Indiana University School of Medicine (E.A.I., M.P.), Indianapolis, Indiana 46202; Kyowa Hakko Kirin Pharma Inc (X.Z., M.A.K., T.I., M.V., J.S.H.), Princeton, New Jersey 08540; Houston Methodist Hospital (M.D.R.), Houston, Texas 77030; Duke University Medical Center (T.J.W.), Durham, North Carolina 27710; Shriners Hospital for Children (F.H.G.), Montreal, Quebec H3G 1A6, Canada; University of California (A.A.P.), San Francisco, California 94143; and Yale Center for X-Linked Hypophosphatemia (K.I., T.O.C.), Yale University School of Medicine, New Haven, Connecticut 06520.
• J. Clin. Endocrinol. Metab. 2015 Jul 1; 100 (7): 2565-73.

ContextIn 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.ObjectiveThe objective was to test the hypothesis that monthly KRN23 (anti-FGF23 antibody) would safely improve serum Pi in adults with XLH.DesignTwo sequential open-label phase 1/2 studies were done.SettingSix academic medical centers were used.ParticipantsTwenty-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).InterventionKRN23 was injected sc every 28 days.Main Outcome MeasureThe main outcome measure was the proportion of subjects attaining normal serum Pi and safety.ResultsAt 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. During dose escalation, TmP/GFR, Pi, and 1,25(OH)2D increased, peaking at 7 days for TmP/GFR and Pi and at 3-7 days for 1,25(OH)2D, remaining above (TmP/GFR, Pi) or near [1,25(OH)2D] 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)2D levels increased transiently, mean serum and urinary calcium remained normal. KRN23 treatment increased biomarkers of skeletal turnover and had a favorable safety profile.ConclusionsMonthly KRN23 significantly increased serum Pi, TmP/GFR, and 1,25(OH)2D in all subjects. KRN23 has potential for effectively treating XLH.

32 keywords...

hide…