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Antibody against FGF23 of potential benefit to patients with XLH
DOI:10.1038/bonekey.2014.120
Patients with X-linked hypophosphatemia (XLH) took part in a small phase I trial to determine the immunogenicity, pharmacodynamics, pharmacokinetics and safety and tolerability of KRN23, a human antibody active against FGF23.
This genetic form of rickets is due to mutations in the gene that encodes phosphate-regulating endopeptidase (PHEX) results in increased levels of serum FGF23, low serum phosphate and 1,25 dihydroxyvitamin D (1,25(OH)2D) as well as decreased phosphate reabsorption by the kidneys. KRN23 has been developed specifically to treat XLH but this is the first time that patients have received it.
A total of 38 XLH patients were given either placebo or a single dose of KRN23 (0.1– 1 mg per kg subcutaneously or 0.003–0.3 mg per kg intravenously). Compared with the XLH in the placebo group, the KRN23 treated patients developed a significantly higher maximum renal tubular threshold for reabsorption of phosphate. They also showed increased serum phosphate levels and 1,25(OH)2D (P<0.01).
The beneficial impact on serum phosphate was greater in the patients given KRN23 subcutaneously; no treated patients developed an immune response to KRN23 or showed serious adverse effects such as hypercalcaemia or elevated creatinine.
Editor’s comment: This is the first clinical trial reporting the PK/PD characteristics of an FGF-23 antibody administered intravenously or subcutaneously. It shows a dose-dependent increase in phosphate tubular reabsorption, serum phosphate and 1,25OHD levels in patients with XLH, thereby offering the promise of an effective treatment for these patients.
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