FDA approves first treatment for rare form of rickets

The FDA on Tuesday approved burosumab, a monoclonal antibody for the treatment of a rare, inherited form of rickets, the agency announced in a press release.

The condition, known as X-linked hypophosphatemia, or XLH, causes low levels of phosphorus in the blood caused by excess fibroblast growth factor 23 (FGF23) production, leading to impaired bone growth and development in children and adolescents and problems with bone mineralization throughout a person’s life. It affects approximately 3,000 children and 12,000 adults in the U.S. In children, XLH causes rickets that leads to lower-extremity deformity, delayed growth and decreased height. Adults with XLH have an increased risk for fractures.

Burosumab (Crysvita, Ultragenyx) is designed to bind the excess FGF23 in these patients, normalizing phosphorus levels, improving bone mineralization, improving rickets in children and healing fractures in adults.

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

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 vs. 8% of those receiving placebo. In children, 94% to 100% of patients treated with burosumab every 2 weeks achieved normal phosphorus levels.

In children and adults, X-ray findings associated with XLH improved with burosumab therapy.

The most common adverse reactions in adults assigned 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.

Burosumab was granted breakthrough therapy designation, under which the FDA provides intensive guidance to the company on efficient drug development and expedites its review of drugs that are intended to treat serious conditions in which clinical evidence shows the drug may represent a substantial improvement over other available therapies. Burosumab also received orphan drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases.

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.

“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,” Emil D. Kakkis, MD, PhD, CEO and president of Ultragenyx, said in a statement after the FDA approval. “This milestone represents Ultragenyx’s second approved therapy in less than 6 months and validates our strategy to rapidly transform good science into effective therapies for rare diseases. This approval would not have been possible without the patients, their families and clinicians who participated and I would like to thank them for their commitment and dedication.”

Kyowa Kirin International, a wholly owned subsidiary of Kyowa Hakko Kirin, and Ultragenyx collaborated in the development and commercialization of burosumab globally, based on the collaboration and license agreement between Kyowa Hakko Kirin and Ultragenyx.