Long-Term Burosumab Administration is Safe and Effective in Adults With X-Linked Hypophosphatemia (XLH)

Abstract Context Burosumab was developed as a treatment option for patients with the rare, lifelong, chronically debilitating, genetic bone disease X-linked hypophosphatemia (XLH). Objective Collect additional information on the safety, immunogenicity, and clinical response to long-term administration of burosumab. Design, Setting, and Patients UX023-CL203 (NCT02312687) was a phase 2b, open-label, single-arm, long-term extension study of adult subjects with XLH who participated in KRN23-INT-001 or KRN23-INT-002 studies. The long term UX023-CL203 study (January 5, 2015 through November 30, 2018) provided data up to 184 weeks. Interventions Participants of UX023-CL203 received burosumab based on the last dose in the prior KRN23-INT-001 or KRN23-INT-002 studies (0.3, 0.6, or 1.0 mg/kg given by subcutaneous injection every four weeks). At Week 12, burosumab could be titrated upward/downward to achieve fasting serum phosphate levels within the normal range. Main Outcome Measures Primary objectives included long-term safety, the proportion of subjects achieving fasting serum phosphate in the normal range, changes in bone turnover markers, patient reported outcomes (PRO) for pain and stiffness, and measures of mobility. Results Fasting serum phosphate levels at the midpoint of the dosing interval (two weeks post-dose, the time of peak effect), were within the normal range in 85-100% of subjects. Measures of phosphate metabolism and bone biomarkers generally improved with burosumab therapy, approaching or reaching their respective normal ranges by study end. Improvements in PRO and mobility were sustained throughout the observation period. No new safety findings emerged with longer-term burosumab treatment. Conclusions These data support the conclusion that burosumab therapy may be a safe and effective long-term treatment option for adult patients with XLH.