FDA approves Crysvita (burosumab-twza)

April 17, 2018, The U.S. Food and Drug Administration today approved Crysvita (burosumab-twza), the first drug approved to treat adults and children ages 1 year 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, M.D., 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 is a serious disease affecting 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 Crysvita were studied in four clinical trials. In the placebo-controlled trial, 94 percent of adults receiving Crysvita once a month achieved normal phosphorus levels compared to 8 percent of those receiving placebo. In children, 94 to 100 percent of patients treated with Crysvita every two weeks achieved normal phosphorus levels. In both children and adults, X-ray findings associated with XLH improved with Crysvita therapy. Comparison of the results to a natural history cohort also provided support for the effectiveness of Crysvita.

The most common adverse reactions in adults taking Crysvita 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 (fever).

Crysvita 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 where clinical evidence shows the drug may represent a substantial improvement over other available therapies. Crysvita 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.

What is the drug for?

CRYSVITA is a drug for the treatment of a genetic form of rickets called X-linked hypophosphatemia, in patients 1 year of age and older.

X-linked hypophosphatemia (XLH) is a rare inherited disorder characterized by low levels of phosphate in the blood which causes soft, weak bones (rickets).

How is this drug used?

CRYSVITA is an injection given under the skin by a healthcare provider. The dose is based on body weight. In pediatric patients, CRYSVITA is given every 2 weeks. In adults, CRYSVITA is given every 4 weeks.

What are the benefits of this drug?

In children with X-linked hypophosphatemia, treatment with CRYSVITA increased phosphate levels in the blood and improved bone abnormalities of rickets at the knee and wrist. In adults, CRYSVITA increased the phosphate levels in the blood.

Were there any differences in how well the drug worked in clinical trials among sex, race and age?

• Sex: CRYSVITA worked similarly in males and females.
• Race: The majority of patients were White. The number of patients in other races was limited; therefore, differences in response among races could not be determined.
• Age: CRYSVITA worked similarly in patients younger and older than 50 years of age.