FDA Approves Burosumab for X-linked Hypophosphatemia, A Rare Form of Rickets

The U.S. Food and Drug Administration today approved burosumab (Crysvita, Ultragenyx) as the first treatment for x-linked hypophosphatemia (XLH) in adults and children ages 1 and older.

The serious condition leaves children with bowed legs, short stature, and bone and dental pain. Adults with XLH may experience joint pain, impaired mobility, tooth abscesses, and hearing loss. Adults with XLH are also at greater risk of bone fractures. In the United States, XLH affects an estimated 3000 children and 12,000 adults.

“XLH differs from other forms of rickets in that vitamin D therapy is not effective,” stated Julie Beitz, MD, director of the Office of Drug Evaluation III in the FDA’s Center for Drug Evaluation and Research. “This is the first FDA-approved medication for the treatment of XLH and a real breakthrough for those living with this serious disease.”

In a placebo-controlled trial, 94% of adults taking burosumab reached normal phosphorous levels compared to only 8% of participants in the placebo group. In children, 94% to 100% of patients reached normal phosphorus levels when treated.

The most common adverse reactions in adults taking burosumab were back pain, headache, restless leg syndrome, decreased vitamin D, dizziness and constipation. The most common adverse reactions in children were headache, injection site reaction, vomiting, decreased vitamin D, and fever.

The rare, hereditary disorder is characterized by renal phosphate wasting caused by excess fibroblast growth factor 23 (FGF23) production. FGF23 causes phosphate urinary excretion and hampers kidney production of vitamin D. Burosumab is an antibody that binds the excess FGF23 in XLH 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 D. Kakkis, MD, PhD, Chief Executive Officer and President of Ultragenyx.

The FDA previously granted the drug a Breakthrough Therapy designation as well as Orphan Drug designation. With this approval, the FDA issued a Rare Pediatric Disease Priority Review Voucher to Ultragenyx, which grants priority review to a future drug application that would not otherwise qualify for Priority Review. This program is intended to promote the development of drugs and biologics for treating rare pediatric conditions.

“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, MD, the lead study investigator, Director of the Yale Center for X-Linked Hypophosphatemia, and Professor of Pediatric Endocrinology at Yale University School of Medicine. “I expect it to revolutionize the care of patients with XLH.”