On Jun. 18, 2020, Ultragenyx Pharmaceutical and Kyowa Kirin announced that the U.S. Food and Drug Administration (FDA) had approved Crysvita® (burosumab) for the treatment of fibroblast growth factor 23 (FGF23)-related hypophosphatemia in tumor-induced osteomalacia (TIO) associated with phosphaturic mesenchymal tumors that cannot be curatively resected or localized in adults and pediatric patients 2 years of age and older. Crysvita is a human antibody that blocks excess activity of FGF23, a hormone that causes phosphate urinary excretion and suppresses active vitamin D production by the kidney.

TIO is a rare disease caused by typically benign, slow-growing tumors that produce excess levels of FGF23, which is involved in phosphate reabsorption. Patients with TIO can experience symptoms including severe hypophosphatemia (low levels of phosphate in the blood), osteomalacia (softening of the bones), muscle weakness, fatigue, bone pain and fractures. There are an estimated 500 to 1,000 people in the United States with TIO, and approximately half of all cases are believed to be inoperable. In patients for whom the tumor or lesion is inoperable, the current treatment consists of oral phosphate and/or active vitamin D replacement. Efficacy of this management is often limited, and its benefits must be balanced with monitoring for potential risks.

This is the second FDA-approved indication for Crysvita, which was first approved in April 2018 for the treatment of X-linked hypophosphatemia (XLH) in adult and pediatric patients one year of age and older. The XLH indication was expanded in September 2019 to include infants as young as six months of age.

The FDA approval of Crysvita for TIO was based on data from two single-arm Phase 2 studies, a 144-week study in 14 adult patients conducted by Ultragenyx in the United States and an 88-week study in 13 adult patients conducted by Kyowa Kirin in Japan and South Korea. In both studies, Crysvita was associated with increases in serum phosphorus and serum 1,25-dihydroxyvitamin D levels. Increased phosphate levels led to improvements in osteomalacia. Additionally, whole body bone scans demonstrated reduced tracer uptake with long-term treatment suggesting healing of bone lesions. Most common adverse reactions (>10%) in TIO patients are: tooth abscess, muscle spasms, dizziness, constipation, injection site reaction, rash, and headache.

The FDA granted Priority Review designation for the supplemental BLA for TIO, which is reserved for drugs that treat a serious condition and, if approved, would provide a significant improvement in safety or effectiveness.