The Food and Drug Administration has approved burosumab to treat X-linked hypophosphatemia, a rare, heritable form of rickets, in adults and children at least 1 year of age. Burosumab received expedited review by the FDA as a breakthrough therapy, and it also has been designated an orphan drug.
X-linked hypophosphatemia (XLH) “differs from other forms of rickets in that vitamin D therapy is not effective. This is the first FDA-approved medication for the treatment of XLH and a real breakthrough for those living with this serious disease,” said, in an FDA announcing the approval of the fully human monoclonal antibody. Dr. Beitz is director of the Office of Drug Evaluation III in the FDA’s Center for Drug Evaluation and Research.
Four clinical trials formed the basis for the FDA’s approval of burosumab. A pivotal randomized, placebo-controlled, double-blindthat randomized 134 patients 1:1 to subcutaneous burosumab or placebo found that normal phosphorus levels were achieved in 94% of adults receiving burosumab, compared with 8% of those who received placebo.
For children, biweekly burosumab resulted in normal phosphorus levels for 94%-100% of participants. Significant skeletal radiographic improvement also was seen for adults and children taking burosumab.
In both adults and children, burosumab had a good safety profile, with no significant changes in serum or urine levels of calcium or in serum levels of intact parathyroid hormone.
is variable in severity; many patients with XLH will have bone pain, bowed legs, and a waddling gait; enthesopathy with associated joint pain; and dental problems and pain. Many also have short stature and, unlike rickets caused by dietary deficiency and some malabsorption problems, XLH is not improved by conventional vitamin D therapy.
The rare disorder, affecting about 3,000 children and 12,000 adults in the United States, is caused by a mutation in the PHEX gene, with resultant overactivity of fibroblast growth factor 23 (FGF23). Burosumab binds FGF23, increasing renal tubular reabsorption of phosphorus and 1,25-dihydroxycholecalciferol, also called calcitriol.
Previously, XLH had been treated by frequent oral supplementation with phosphate and calcitriol. Burosumab will be marketed by Ultragenyx Pharmaceutical as Crysvita. It is given as a once-monthly or biweekly subcutaneous injection.