Kidney Week

Abstract: TH-OR023

Burosumab Improves Phosphorus Metabolism and Fracture Healing in Adults with X-Linked Hypophosphatemia (XLH)

Session Information

• CKD-MBD: Phosphorus, FGF-23, and Trials
  October 25, 2018 | Location: 33C, San Diego Convention Center
  Abstract Time: 04:54 PM - 05:06 PM

Category: Bone and Mineral Metabolism

• 402 Bone and Mineral Metabolism: Clinical

Authors

• Portale, Anthony A., University of California San Francisco, San Francisco, California, United States

Anthony A. Portale, MD

• Insogna, Karl, Yale University, New Haven, Connecticut, United States

Karl Insogna,

• Imel, Erik, Indiana University School of Medicine, Indianapolis, Indiana, United States

Erik Imel,

• Kamenicky, Peter, Université Paris-Sud, Le Kremlin-Bicêtre, France

Peter Kamenicky,

• Imanishi, Yasuo, Osaka City Univ Graduate School of Med, Abeno-ku, Osaka-Fu, Japan

Yasuo Imanishi,

• Ito, Nobuaki, University of Tokyo Hospital, Tokyo, Japan

Nobuaki Ito,

• Perwad, Farzana, University of California San Francisco, San Francisco, California, United States

Farzana Perwad,

• Zhang, Lin, Ultragenyx Pharmaceutical Inc, Novato, California, United States

Lin Zhang,

• Theodore-Oklota, Christina, Ultragenyx Pharmaceutical Inc., Novato, California, United States

Christina Theodore-Oklota,

• Mealiffe, Matt, Ultragenyx Pharmaceutical Inc., Novato, California, United States

Matt Mealiffe,

• San martin, Javier, Ultragenyx Pharmaceutical Inc., Novato, California, United States

Javier San martin,

• Carpenter, Thomas, Yale University, New Haven, Connecticut, United States

Thomas Carpenter,

Background

In an ongoing, Phase 3, double-blind, multicenter study, we examined the efficacy and safety of burosumab, a human monoclonal antibody against FGF23, in 134 adults with XLH.

Methods

Subjects were randomized 1:1 to receive burosumab 1 mg/kg (n=68) or placebo (n=66) subcutaneously every 4 weeks (wks). After 24 wks, subjects receiving placebo crossed-over to receive burosumab, and all subjects received burosumab during wks 24-48, while remaining blinded to prior treatment.

Results

From wks 0 to 24, a significantly greater percentage of burosumab subjects than placebo subjects (94% vs 8%; p<0.0001) attained the primary endpoint of a mean serum phosphorus level within the normal range at the midpoint of dosing intervals; from wks 24-48, phosphorus was within the normal range in both groups (crossover 89%, burosumab-continuation 84%). At baseline, 65 active fractures/pseudofractures (Fx/PFx) were present in 47% (32/68) of subjects in the burosumab group and 91 Fx/PFx in 58% (38/66) of subjects in the placebo group. At wk 24, 43% (28/65) of Fx/PFx fully healed with burosumab and 8% (7/91) healed with placebo (odds ratio of full healing 16.8, p<0.0001). By wk 48, the burosumab-continuation group showed additional Fx/PFx healing, and the crossover group showed healing similar to that of the burosumab-continuation group at wk 24. At wk 48, both groups showed significant decreases from baseline (or wk 24 for crossover) in stiffness, physical functioning, and pain scores (all p<0.001). At wk 48, PTH decreased from baseline by 9% in the burosumab-continuation group and by 7% in the crossover group. Serum creatinine and calcium levels and urine calcium excretion were unchanged. Most subjects had no change in nephrocalcinosis severity score (5-point scale), and no subject had a change >±1 point. Serious AEs were reported in 15 subjects; none were assessed as drug-related.

Conclusion

Inhibition of FGF23 with burosumab was associated with improvements in serum phosphorus levels, pain, stiffness, and physical functioning, and healing of Fx/PFx in adults with XLH. The improvements seen with burosumab at wk 24 were replicated in placebo subjects who crossed over to receive burosumab from wks 24-48.

Funding

• Commercial Support – Ultragenyx Pharmaceutical Inc.