FDA Approves Bone-Softening Disorder Treatment Crysvita

The U.S. Food and Drug Administration (FDA) approved Crysvita (burosumab) for the treatment of a rare disease, tumor-induced osteomalacia (TIO), a disease that can cause a softening in the bones of the body.

The FDA greenlit Crysvita under Priority Review. Crysvita is a drug developed by Ultragenyx Pharmaceutical and Tokyo-based Kyowa Kirin Co. Ltd., a specialty pharmaceutical company. Specifically, Crysvita was approved for the treatment of fibroblast growth factor 23 (FGF23)-related hypophosphatemia in TIO associated with phosphaturic mesenchymal tumors that cannot be curatively resected or localized in adults and pediatric patients two 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 slow-growing tumors that produce excess levels of FGF23, which is involved in phosphate reabsorption. Patients with TIO can experience a number of symptoms including severe hypophosphatemia, which is low levels of phosphate in the blood, softening of the bones known as osteomalacia, 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. For those patients, current treatment typically consists of oral phosphate and active vitamin D replacement. 

The FDA approval of Crysvita for TIO was based on data from two single-arm Phase II studies. 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.

“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,” Camille L. Bedrosian, chief medical officer of Ultragenyx said in a statement. “We plan to leverage our experience and existing infrastructure with Crysvita in X-linked hypophosphatemia to bring this important medicine to patients living with the rare, painful and debilitating disorder of TIO.”

This approval marks the second FDA-approved indication for Crysvita. The medication 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.

“Since its approval, Crysvita has meant a great deal to patients and families that previously had no other treatment options.  We are proud of the work that has been done to advance this discovery from our labs, through a robust clinical research program, and through the FDA’s priority review process, to make this treatment available to patients with TIO,” Gary Zieziula, Kyowa Kirin’s president of North American operations said in a statement.