The FDA has approved
Ultragenyx and Kyowa Hakko Kirin’s burosumab-twza (Crysvita) for the treatment of X-linked hypophosphatemia (XLH) in adult and pediatric patients aged 1 year or older.
XLH is a rare, hereditary, progressive, and lifelong skeletal disorder that is characterized by renal phosphate wasting caused by excess production of fibroblast growth factor 23 (FGF23), which suppresses active vitamin D production by the kidney. In children, XLH can cause rickets, delayed growth, and decreased height, and adults with XLH have an increased risk of fracture.
Burosumab, a recombinant, fully human monoclonal antibody, works by blocking FGF23, and can normalize phosphorous levels, improve bone mineralization, improve rickets in children, and promote fracture healing in adults.
The FDA approval for the pediatric population is supported by 64-week data from a study in 52 patients, aged 5 to 12 years, which showed improvement in patients’ rickets, increased serum phosphorous levels, decreased serum alkaline phosphatase activity, and increased growth. The indication is also supported by 40-week data from an open-label study in 13 patients aged 1 to 4 years.
The adult indication is supported by 24-week data in a randomized, double-blind, placebo-controlled study in 134 adults. Treatment with burosumab resulted in a higher proportion of patients achieving serum phosphorous levels above the lower limit of normal, and a higher rate of complete healing of active fractures, versus placebo. Data from a 48-week open-label study showed healing of ostomalacia.
Lead investigator Tom Carpenter, MD, director of the Yale Center for X-Linked Hypophosphatemia and professor of pediatric endocrinology at Yale University School of Medicine, called approval of the drug a “watershed moment” for patients with XLH, as it is the first drug that has the potential to correct renal phosphate wasting.
investors in a conference call that it is focused on providing access to the treatment for patients who need it. Burosumab will be available in 10-, 20-, and 30-mg vials; the 10-mg vial will cost $3400, and the larger vials will be priced linearly. The recommended dosage for children is 0.8 mg per kg, which will be administered once every 2 weeks. Adults will receive doses of 1 mg per kg, up to a maximum of 90 mg, every 4 weeks.
Taking the rebates that it expects to negotiate into consideration, Ultragenyx said that burosumab will cost approximately $160,000 per patient per year for children and $200,000 per patient per year for adults, depending on body weight. The company said that it does not plan to increase costs in the early years of the drug’s availability.
Steven B. Miller, MD, chief medical officer of pharmacy benefit manager (PBM) Express Scripts, told
Forbes that “It’s not inexpensive, but I do believe the right word is responsible,” and added that the cost of the drug is “going to be a very reasonable tradeoff” considering the surgical interventions that patients currently require for XLH. By comparison, said Miller, other genetic diseases that cause similar levels of disability have treatments that cost $600,000 or more per year.