Ultragenyx Pharmaceutical, Kyowa Hakko Kirin, and Kyowa Kirin International reported positive results from a 48-week late-stage study of burosumab, their experimental therapy to treat adults with X-linked hypophosphatemia (XLH), a rare genetic disorder that results in poor bone health because of a lack of phosphorus in the blood.

Patients with XLH can experience abnormal bone formation, bone pain, lower than normal bone density, fractures, short stature, tooth abscesses, tinnitus, deformities in the legs, waddling gait, muscle pain and weakness. Adults with condition may develop arthritis, a decreased ability to move; and bone, muscle, and joint pain. They can also develop abnormalities where the ligaments and tendons attach to the bone, suffer fractures, and experience a softening of the bones.

Burosumab is an investigational recombinant fully human monoclonal IgG1 antibody, discovered by Kyowa Hakko Kirin, against the phosphaturic hormone fibroblast growth factor 23 (FGF23). FGF23 is a hormone that reduces serum levels of phosphorus and active vitamin D by regulating phosphate excretion and active vitamin D production by the kidney. The companies are also developing burosumab as a treatment for tumor-induced osteomalacia, which causes bone pain, fractures, and muscle weakness due to elevated levels of FGF23.

The late-stage study is a randomized, double-blind, placebo-controlled clinical trial designed to assess the efficacy and safety of burosumab administered every four weeks in 134 adult XLH patients in the United States, European Union, Canada, Japan, and South Korea. The primary endpoint of the study is the percentage of patients who achieved average serum phosphorus levels in the normal range over 24 weeks. Secondary and other endpoints include pain, stiffness, and physical function, radiographic healing of active fractures/pseudofractures, and safety. After 24 weeks, all patients receive burosumab through the 72-week open-label extension period of the study.

Treatment with burosumab for 48 weeks showed sustained maintenance of normal serum phosphorus levels and further improvement in stiffness, physical function and pain. Patients who crossed over from placebo to burosumab after 24 weeks showed normalization of serum phosphorus and improvement in stiffness, pain and physical functioning. An increased rate of fracture healing, in favor of burosumab treated patients, was observed during the first 24 weeks of burosumab treatment and this increased up to 48 weeks of treatment.

Placebo patients who crossed over to burosumab showed a similar increased rate of fracture healing. The safety profile was consistent with what has been previously observed in this study and in other open label studies of burosumab in adults and children. Ultragenyx is conducting the study under a collaboration and license agreement with Kyowa Hakko Kirin.  Burosumab is being developed by Ultragenyx, Kyowa Hakko Kirin and Kyowa Kirin International.

“This longer-term data on symptom improvement and fracture healing support burosumab’s potential value in treating serious disease symptoms and promoting bone healing in adult patients with XLH,” said Emil Kakkis, president and CEO of Ultragenyx. “The continued clinical improvements in patients and the new data demonstrating a significant decrease in pain medication use after treatment with burosumab provide further support for the potential value in the treatment of adults with XLH.”

There was no difference in the overall frequency of treatment emergent serious and non-serious adverse events, treatment related adverse events and serious adverse events between the group who received burosumab for the 48-week period compared to the group who received placebo for the 24-week double-blind period and then crossed over to burosumab.

Of the 134 patients enrolled in the study, one patient in the burosumab arm discontinued treatment during the 24-week double-blind treatment period. During the open-label period, seven patients discontinued treatment. No discontinuations were related to adverse events or tolerability. There has been one non-treatment related death due to a car accident that was reported after the week-48 data cutoff date.

December 4, 2017

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