Rare Daily Staff

The U.S. Food and Drug Administration granted approval to Crysvita, Ultragenyx and Kyowa Kirin International’s treatment of children and adults with X–Linked Hypophosphatemia, a rare and progressive genetic skeletal disorder.

People with XLH can experience abnormal bone formation, bone pain, lower than normal bone density, fractures, short stature, tooth abscesses, tinnitus, deformities in the legs, waddling gait, muscle pain and weakness. Adults with condition may develop arthritis, a decreased ability to move; and bone, muscle, and joint pain. They can also develop abnormalities where the ligaments and tendons attach to the bone, suffer fractures, and experience a softening of the bones.

Crysvita is an antibody that blocks fibroblast growth factor 23, a hormone that causes phosphate urinary excretion and suppresses active vitamin D production by the kidney. Crysvita is designed to bind the excess factor 23 in these patients, normalizing phosphorus levels, improving bone mineralization, improving rickets in children and healing fractures in adults.

“Patients now have an approved breakthrough therapy that can help correct the underlying disease, transforming the treatment of XLH and reducing related bone disease in both children and adults living with this disease,” said Emil Kakkis, president and CEO of Ultragenyx. “This milestone represents Ultragenyx’s second approved therapy in less than six months and validates our strategy to rapidly transform good science into effective therapies for rare diseases.”

“The approval of Crysvita is truly a watershed moment for patients with X-linked hypophosphatemia as it is the first therapy directed toward correction of renal phosphate wasting,” said Tom Carpenter, the lead study investigator, director of the Yale Center for X-Linked Hypophosphatemia, and professor of pediatric endocrinology at Yale University School of Medicine. “By targeting this mechanism Crysvita leads to sustained improvements in phosphate metabolism with concurrent repair of the skeleton, even after prior treatment with conventional approaches.”

Carpenter said he expects Crysvita, which is far less burdensome than for currently available therapies, “to revolutionize the care of patients with XLH.”

The FDA previously granted Crysvita a Breakthrough Therapy designation for the treatment of XLH in pediatric patients one year of age and older, and evaluated Crysvita with Priority Review, which is reserved for drugs that treat a serious condition and, if approved, would provide a significant improvement in safety or effectiveness.

With this approval, the FDA issued a Rare Pediatric Disease Priority Review Voucher, which confers priority review to a subsequent drug application that would not otherwise qualify for Priority Review. The Rare Pediatric Disease Priority Review Voucher program is designed to encourage development of new drugs and biologics for the prevention or treatment of rare pediatric diseases.

Ultragenyx sold the Rare Pediatric Disease Priority Review voucher it was awarded for is MPS VII drug Mepsevii in December for $130 million.

April 17, 2018
Photo: Emil Kakkis, president and CEO of Ultragenyx