Burosumab for TIO

KRN23 is an investigational recombinant fully human monoclonal IgG1 antibody against the phosphaturic hormone Fibroblast Growth Factor 23 (FGF23) in development for tumor-induced osteomalacia (TIO). 

TIO is a disease characterized by typically benign tumors that produce excess levels of FGF23, including its skin lesion variant, epidermal nevus syndrome (ENS). FGF23 is a hormone that reduces serum levels of phosphorus and vitamin D by regulating phosphate excretion and vitamin D production by the kidney. Phosphate-wasting in TIO is caused by excessive levels and activity of FGF23.

TIO is characterized by hypophosphatemia, osteomalacia, muscle weakness, fatigue, bone pain, and fractures.

The symptoms of TIO rapidly resolve if the causal tumors can be resected; however, there are cases in which resection of the tumor is not feasible or recurrence of the tumor occurs after resection. In patients for whom the tumor is inoperable, the current standard of care consists of oral phosphate and/or vitamin D replacement. Efficacy of this treatment is often limited, as it does not treat the underlying disease and its benefits must be balanced with monitoring for potential risks.

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 TIO, 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

Clinical Trials

KRN23 for TIO


Phase 2


Tumor-Induced Osteomalacia (TIO)


500-1,000 US patients

disease mechanism

Excess FGF23 leading to low serum phosphorus levels

key symptoms

Bone and muscle pain
Muscle weakness
Physical impairment

treatment mechanism

Antibody to bind excess FGF23