Long-term Burosumab Administration Is Safe and Effective in Adults With X-linked Hypophosphatemia

J Clin Endocrinol Metab. 2022 Dec 17;108(1):155-165. doi: 10.1210/clinem/dgac518.

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.

Methods: 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. Participants in 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 4 weeks). At Week 12, burosumab could be titrated upward/downward to achieve fasting serum phosphate levels within the normal range. 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 for pain and stiffness, and measures of mobility.

Results: Fasting serum phosphate levels at the midpoint of the dosing interval (2 weeks postdose, the time of peak effect) were within the normal range in 85% to 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 patient-reported outcomes and mobility were sustained throughout the observation period. No new safety findings emerged with longer-term burosumab treatment.

Conclusion: These data support the conclusion that burosumab therapy may be a safe and effective long-term treatment option for adult patients with XLH.

Keywords: FGF23; X-linked hypophosphatemia; XLH; burosumab; fibroblast growth factor 23.

Publication types

  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Monoclonal, Humanized* / administration & dosage
  • Antibodies, Monoclonal, Humanized* / adverse effects
  • Familial Hypophosphatemic Rickets* / drug therapy
  • Genetic Diseases, X-Linked* / drug therapy
  • Humans
  • Phosphates

Substances

  • Antibodies, Monoclonal, Humanized
  • burosumab
  • Phosphates

Associated data

  • ClinicalTrials.gov/NCT02312687