This single arm, open label study enrolled 14 adults with X-linked Hypophosphatemia who received 1.0 mg/kg burosumab monthly, calculated based on baseline weight and up to a maximum dose of 90 mg. The primary endpoint was the percent change from baseline in osteoid volume/bone volume (OV/BV) at week 48. OV/BV is the percent of a given volume of bone tissue that consists of unmineralized bone (osteoid). Ten subjects were assessed for the primary endpoint. The mean percentage change of unmineralized bone at 48 weeks was -54.18. The treatment was generally well tolerated. Two of the 14 subjects reported serious adverse effects (migraine and paraesthesia). Other adverse effects included back pain, headache, tooth infection, restless leg syndrome, vitamin D decreased, dizziness, constipation and blood phosphorus increased.
About X-linked hypophosphatemia
X-linked hypophosphatemia (XLH) is an inherited disorder characterized by low levels of phosphate in the blood. Phosphate levels are low because phosphate is abnormally processed in the kidneys, which causes a loss of phosphate in the urine (phosphate wasting) and leads to soft, weak bones (osteomalacia). XLH is usually diagnosed in childhood. XLH is caused by mutations in the PHEX gene on the X chromosome, and inheritance is X-linked dominant.
Burosumab is a recombinant fully human monoclonal IgG1 antibody against the phosphaturic hormone Fibroblast Growth Factor 23 (FGF23). Adults and children with XLH have increased FGF23 activity. The kidneys are unable to reabsorb phosphorus, leading to low levels in the blood. Thus, phosphorus is not deposited into the bones, leading to the symptoms of XLH. Burosumab blocks the activity of FGF23 and helps to restore phosphorus absorption in the kidneys so the phosphorous can then be deposited into the bones.
The FDA approved burosumab in April of 2018 for children and adults with x-linked hypophosphatemia. It is currently marketed as Crysvita. The FDA granted Crysvita a Rare Pediatric Disease Priority Review Voucher, Breakthrough Therapy designation and Orphan Drug designation.
Ultragenyx and Kyowa Hakko Kirin entered into a collaboration and license agreement in August 2013 to develop and commercialize burosumab.