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

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.

• Authors: Thomas J Weber, Erik A Imel, Thomas O Carpenter, Munro Peacock, Anthony A Portale, Joel Hetzer, J Lawrence Merritt, Karl Insogna
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 108 Issue 1 Pg. 155-165 (12 17 2022) ISSN: 1945-7197 [Electronic] United States
• PMID: 36072994 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society.

Chemical References

• Antibodies, Monoclonal, Humanized
• burosumab
• Phosphates

Topics

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