X-linked hypophosphatemia (XLH) is a heritable form of rickets that results from mutations in the gene encoding the phosphate regulating endopeptidase (PHEX).
Unlike diet-associated forms of rickets, XLH cannot be ameliorated by vitamin D ingestion. XLH patients have increased serum levels of FGF23, which decreases both inorganic phosphate (Pi) and the activated form of vitamin D.
In this issue of the Journal of Clinical Investigation, Thomas Carpenter and colleagues at Yale University evaluated the effectiveness and safety of an anti-FGF23 antibody (KRN23) in a small cohort of XLH patients. A single dose of KRN23 administered intravenously (i.v.) or subcutaneously (s.c.) improved renal phosphate reabsorption, and increased serum Pi and activated vitamin D concentrations, and s.c. administration provided benefit for a longer duration than i.v. dosing.
These findings, along with a favorable safety profile, indicate that KRN23 should be further evaluated for use in XLH patients.