Burosumab for XLH

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

Press Releases

Data Presentations/Publications

Clinical Trials

KRN23 for XLH

Stage

Phase 3

DISEASE

X-Linked Hypophosphatemia (XLH)

PREVALENCE

12,000 US patients

Disease mechanism

Excess FGF23 leads to low serum phosphorus

Key Symptoms

Rickets and bowing
Osteomalacia     Psuedofractures
Growth impairment
Bone and muscle pain
Muscle weakness
Physical function impairment

Treatment mechanism

Antibody to bind excess FGF23