DENVER (FRONTLINE MEDICAL NEWS) – Two studies provide hope for a new treatment of X-linked hypophosphatemia (XLH), a genetic disorder that leads to low phosphorus levels, which can cause rickets in children and a host of bone and other problems in adulthood.

The studies evaluated the use of burosumab, a monoclonal antibody that targets fibroblast growth factor 23 (FGF23). FGF23 is a hormone that reduces serum levels of phosphorus and vitamin D through its effects on the kidney.

“For the first time, this establishes the efficacy of any treatment in adults with XLH,” said Karl L. Insogna, MD, professor of medicine (endocrinology), at Yale University, New Haven, Conn., who presented the phase III study results during a poster session at the annual meeting of the American Society for Bone and Mineral Research. “Even in adults who have a lot of underlying disease burden, which is not likely to be completely reversed by this drug, you can address the underlying pathophysiology of the disease and show not only symptomatic improvement but also healing of fractures and pseudofractures,” he added.

In August, Ultragenyx and Kyowa Hakko Kirin, the companies developing burosumab, submitted a biologic license application for approval to the Food and Drug Administration. Approval would come as a relief to adults with the condition, “who have been largely ignored, and yet they suffer from horrible complications,” said Dr. Insogna, associate director of the Yale Center for X-Linked Hypophosphatemia .

XLH patients may be treated with calcitriol and phosphate, but this requires dosing 3-5 times a day, with side effects that can be onerous. “If you were dealing with a shot, you’d have 100% compliance and (fewer) side effects. It’s going to be a whole lot better,” he noted.

In the phase 3 adult trial, 134 patients were randomized to subcutaneous burosumab (at a dose of 1 mg/kg) or placebo every 4 weeks for 24 weeks. Among those treated with burosumab, 94.1% achieved serum phosphatase levels in the normal range, compared with 7.6% of those on placebo. Among patients taking burosumab, 36.9% of fractures and pseudofractures present at baseline had healed by the end of the study, compared with 9.9% of the fractures and pseudofractures in the placebo group (odds ratio, 7.76; P =.0001).

The two groups had similar safety profiles, with no differences in serum or urine calcium, serum intact parathyroid hormone, or nephrocalcinosis severity score.

In the phase 2 pediatric trial, 52 patients aged 5-12 years received subcutaneous burosumab every other week or once a month for 64 weeks. Although the patients had received vitamin D/phosphate therapy for an average of 7 years before enrollment, rickets was present at baseline (mean Thatcher Rickets Severity Score, 1.8). The dose of burosumab was titrated (maximum dose 2 mg/kg) to achieve age-appropriate fasting serum phosphate. All of the subjects achieved normal fasting serum phosphatase levels, but the values were more stable in the dose treated every other week.

The Thatcher RSS improved overall (–0.92; P less than .0001) in the group dosed every other week (–1.00; P less than .0001) and the group dosed monthly (–0.84; P less than .0001). These changes were more notable in patients with more severe rickets at baseline (RSS, 1.5 or higher), which had a change of –1.44 (P less than .0001).

Similar improvements were seen with the Radiographic Global Impression of Change (RGI-C). Among children with an RSS value of 1.5 or higher, substantial healing (an increase in RGI-C equal to or greater that 2) occurred in the group dosed every other week (82.4%) and the group dosed monthly (70.6%).

There was no evidence of hyperphosphatemia or hypercalcemia, and there were no clinically meaningful changes in urine calcium or serum intact parathyroid hormone levels.

The studies were funded by Ultragenyx and Kyowa Kirin International. Dr. Insogna reported having no financial disclosures.