FDA Clears First Drug for Rare Inherited Form of Rickets

Megan Brooks

April 17, 2018

The US Food and Drug Administration (FDA) has approved the orphan drug burosumab (Crysvita, Ultragenyx Pharmaceutical Inc) to treat adults and children age 1 year and older with X-linked hypophosphatemia (XLH), a rare, inherited, progressive form of rickets.

"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 statement. "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 roughly 3000 children and 12,000 adults in the United States.  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.

XLH is characterized by renal phosphate wasting caused by excess fibroblast growth factor 23 (FGF23) production.  Burosumab is designed to bind the excess FGF23 in patients with XLH, thereby normalizing phosphorus levels, improving bone mineralization, improving rickets in children, and healing fractures in adults, the company explained in a news release

In a placebo-controlled trial, 94% of adults receiving burosumab once a month achieved normal phosphorus levels compared with 8% of those receiving placebo. In children, 94% to 100% of patients treated with burosumab every 2 weeks achieved normal phosphorus levels. In both children and adults, radiograph findings associated with XLH improved with burosumab treatment.

"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," lead study investigator, Tom Carpenter, MD, director, Yale Center for X-Linked Hypophosphatemia, and professor of pediatric endocrinology at Yale University School of Medicine, New Haven, Connecticut, said in the release.

"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. Most importantly, the dosing regimen for Crysvita is far less burdensome than for currently available therapies and should be readily acceptable by families. I expect it to revolutionize the care of patients with XLH," said Carpenter.

The most common adverse reactions in adults treated with burosumab in clinical testing 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 had breakthrough therapy designation from the FDA for the treatment of XLH and was reviewed under the agency's priority review process. This process is reserved for drugs that treat a serious condition and, if approved, would significantly improve safety or effectiveness.

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