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Abstract: FR-OR032

Effects of Long-Term Burosumab, a Fully Human Monoclonal Antibody Against FGF23, on Phosphorus, Calcium, and Nephrocalcinosis in Adults with X-Linked Hypophosphatemia

Session Information

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
  • Carpenter, Thomas, Yale University, New Haven, Connecticut, United States
  • Imel, Erik, Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Jan de beur, Suzanne, John Hopkins University, Balitmore, Maryland, United States
  • Zhang, Lin, Ultragenyx Pharmaceutical Inc, Novato, California, United States
  • Rees, Linda, Ultragenyx Pharmaceutical Inc., Novato, California, United States
  • Chang, Ting, Ultragenyx, Novato, California, United States
  • San martin, Javier, ultragenyx, Novato, California, United States
  • Insogna, Karl, Yale University, New Haven, Connecticut, United States
Background

In XLH, nephrocalcinosis and hyperparathyroidism are complications of treatment with oral phosphate and active vitamin D. Burosumab significantly improved serum phosphorus, fracture/pseudofracture healing, stiffness, and physical functioning compared to placebo in a Phase 3, double-blind, multicenter study in adults with XLH (CL303, NCT02526160). Here, we evaluate the effects of long-term burosumab on nephrocalcinosis and related measures using data from the completed trial.

Methods

134 subjects were randomized 1:1 to receive burosumab 1 mg/kg or placebo subcutaneously every 4 weeks. At Week 24, subjects receiving placebo crossed-over to receive burosumab, and all subjects remained on burosumab up to Week 96, remaining blinded to prior treatment. Groups were combined for the Week 96 analysis. Nephrocalcinosis score determined by ultrasound, ranging from 0 (normal) to 4 (stone formation), was assessed by central readers blinded to treatment.

Results

90% (121/134) of subjects had previously received oral phosphate and active vitamin D. At baseline, nephrocalcinosis was present in 54% (73/134) of subjects, with scores of 1, 2, and 3 observed in 41%, 12%, and 1%, respectively. At Week 96, nephrocalcinosis score remained unchanged from baseline in most subjects (101/120, 84%), decreased by 1 in 9 subjects (8%), and increased by 1 in 10 subjects (8%). Serum phosphorus levels and TmP/GFR increased significantly with burosumab. Serum calcium and GFR remained stable, and mean PTH decreased modestly. Urine calcium trended upward, with 4 (3%) subjects having values above the ULN at Week 96.

Conclusion

In adults with XLH receiving burosumab for 96 weeks, renal phosphate reabsorption and serum phosphorus increased significantly and PTH decreased toward normal levels. Mean urine calcium excretion increased slightly, but nephrocalcinosis scores were not significantly changed.

VisitSerum
Calcium,
mg/dL
Serum
PTH,
pg/mL
Serum
1,25(OH)2D,
pg/mL
Urine Calcium Excretion,
mg/24-hour
Serum
Phosphorus,
mg/dL
TmP/GFR,
mg/dL
Baseline9.15 (0.45)97 (51)33 (14)102 (57)1.98 (0.31)1.64 (0.39)
Week 489.09 (0.44)87 (40)40 (14)117 (66)2.47 (0.47)2.21 (0.56)
Week 729.12 (0.40)78 (39)38 (14)124 (63)2.49 (0.45)2.19 (0.52)
Week 969.10 (0.40)79 (36)34 (11)145 (99)2.42 (0.46)2.07 (0.52)

Data are mean (SD); Measurements were assessed at the end of the dose interval