FDA Approves First Therapy for Rare Inherited Form of Rickets

Drug normalized phosphorus levels and improved x-ray findings in trials

The FDA has approved burosumab-twza (Crysvita, Ultragenyx Pharmaceutical), the first drug approved to treat adults and children 1 year of age and older with x-linked hypophosphatemia (XLH), a rare, inherited form of rickets. XLH causes low levels of phosphorus in the blood. It leads to impaired bone growth and development in children and adolescents and problems with bone mineralization throughout a patient’s life.

“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.”

XLH affects approximately 3,000 children and 12,000 adults in the United States. Most children with XLH experience bowed or bent legs, short stature, bone pain, and severe dental pain. Some adults with XLH experience persistent discomfort or complications, such as joint pain, impaired mobility, tooth abscesses, and hearing loss.

The safety and efficacy of burosumab were studied in four clinical trials. In the placebo-controlled trial, 94% of adults receiving burosumab once a month achieved normal phosphorus levels compared to 8% of those receiving placebo. In children, 94% to 100% of patients treated with burosumab every two weeks achieved normal phosphorus levels. In both children and adults, x-ray findings associated with XLH improved with burosumab therapy. Comparison of the results to a natural history cohort also provided support for the effectiveness of burosumab.

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 pyrexia.

Burosumab was granted FDA breakthrough therapy and orphan drug designations. The sponsor is receiving a rare pediatric disease priority review voucher under a program intended to encourage development of new drugs and biologics for the prevention and treatment of rare pediatric diseases. A voucher can be redeemed at a later date to receive priority review of a subsequent marketing application for a different product. This is the 14th rare pediatric disease priority review voucher issued by the FDA since the program began.

Source: FDA; April 17, 2018.