KRN23 is an investigational recombinant fully human monoclonal IgG1 antibody against the phosphaturic hormone Fibroblast Growth Factor 23 (FGF23) in development for X-Linked Hypophosphatemia (XLH).
XLH is a bone disease characterized by phosphate-wasting due to excess activity of FGF23. FGF23 is a hormone that reduces serum levels of phosphorus and vitamin D by regulating phosphate excretion and vitamin D production by the kidney. Low phosphate levels lead to inadequate mineralization of bone, which leads to a spectrum of skeletal abnormalities, physical impairment, weakness, and pain.
Most pediatric patients and some adult patients are managed using oral phosphate replacement and vitamin D (calcitriol) therapy, which requires frequent divided doses and careful medical monitoring. It is partially effective at reducing rickets in pediatric patients, but it does not improve growth and can be challenging to optimize the dose without increasing the risk of depositing phosphate-calcium precipitates in the kidneys (nephrocalcinosis).
Ultragenyx and Kyowa Hakko Kirin entered into a collaboration and license agreement in August 2013 to develop and commercialize KRN23.
Mechanism of Action
KRN23 is designed to bind to and thereby inhibit the excessive biological activity of FGF23. By blocking excess FGF23 in patients with XLH, KRN23 is intended to restore normal phosphate reabsorption from the kidney and increase the production of vitamin D, which enhances intestinal absorption of phosphate and calcium.
News & Other Information
- Phase 2 64-week results (n=52) in pediatric XLH patients - ICCBH 2017 (pdf)
- Phase 2 patient-reported outcomes at 64 weeks (n=52) in pediatric XLH patients – ICCBH 2017 (pdf)
- Phase 2 24-week results in pediatric XLH patients < 5 years old – ICCBH 2017 (pdf)
- Phase 2 48-week results from extension study in adult XLH patients - WCO-IOF-ESCEO 2017 (pdf)
- Pediatric XLH disease burden survey results - ICCBH 2015 (pdf)
- Adult XLH disease burden survey results - ENDO 2015 (pdf)
- Phase 3 Adult Placebo-Controlled Study (link)
- Phase 3 Adult Open-Label Osteomalacia Study (link)
- Phase 2 Pediatric Study (link)
- Phase 2 Adult Long-Term Extension Study (link)