RARE Daily

Ultragenyx and Kyowa Kirin’s Crysvita Approved for the Treatment of Tumor-Induced Osteomalacia

June 19, 2020

Rare Daily Staff

The U.S. Food and Drug Administration approved Crysvita for the treatment of patients two years of age and older with tumor-induced osteomalacia who cannot undergo surgical removal of tumors.

Tumor-induced osteomalacia (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, which provides limited benefits and must be balanced with monitoring for potential risks.

Crysvita is a human antibody, discovered by Kyowa Kirin, that blocks excess activity of FGF23, a hormone that causes phosphate urinary excretion and suppresses active vitamin D production by the kidney.

“For approximately half of all individuals with TIO, surgical removal of the tumors is not possible, leaving these patients with no other treatment options. The FDA approval of Crysvita marks the first treatment option that addresses the cause of the severe hypophosphatemia and osteomalacia resulting from these rare tumors,” said Camille Bedrosian, chief medical officer of Ultragenyx.

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 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.

Kyowa Kirin and Ultragenyx have been collaborating in the development and commercialization of Crysvita globally based on the collaboration and license agreement between the parties in 2013.

Photo: Camille Bedrosian, chief medical officer of Ultragenyx


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