ESPE Abstracts (2016) 86 S1.1

Innovative Therapies in Bone and Mineral Metabolism: Anti FGF23 in X-linked Hypophosphatemia

Thomas Carpenter


Background: Hypophosphatemia due to excess urinary phosphate losses and rachitic bone disease occur in several related disorders. The most common form of the heritable hypophosphatemic disorders, X-linked hypophosphatemia (XLH), is due to loss-of-function mutations of the osteocyte/osteoblast protein, PHEX. Reduced abundance of phosphate transporters on the luminal surface of renal tubular cells in the syngeneic animal model of XLH, and inappropriately normal (or frankly low) circulating levels of 1,25 dihydroxyvitamin D (1,25D) are characteristic of the disease. Thus currently available therapies for XLH employ supplementation with phosphate and 1,25D.

Objective and hypotheses: Current replacement with phosphate and 1,25D is cumbersome, and fraught with complications. As the excessive renal phosphate losses and reduced capacity to maintain normal circulating 1,25D levels appear to be direct effects of increased FGF23 activity, we hypothesized that inhibition of FGF23 would serve to ameliorate the primary renal abnormalities, and restore a milieu conducive to the restoration of mineralization.

Method: This talk will review potential strategies to improve therapeutic outcomes for children and adults with XLH, focusing on several clinical studies using an anti-FGF23 inhibitory antibody (KRN23).

Results: Administration of KRN23 every 2–4 weeks corrects serum phosphate and improved 1,25D in adults and children. Improved patient-reported outcomes have been documented in adults and radiographic improvement in rickets scores is evident in growing children.

Conclusion: Patients affected with XLH would benefit from a more effective and better-tolerated therapy than the currently available approaches. Inhibition of FGF23 activity using an anti-FGF23 inhibitory antibody appears to be a safe and effective strategy to improve biochemical status, rickets, and well-being for patients with this disorder.

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