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Abstract: PO0409

Nephrocalcinosis at Baseline Did Not Increase the Risk of Nephrocalcinosis Progression After Long-Term Burosumab Treatment in Adults and Children with X-Linked Hypophosphatemia (XLH)

Session Information

Category: Bone and Mineral Metabolism

  • 402 Bone and Mineral Metabolism: Clinical

Authors

  • Perwad, Farzana, University of California, San Francisco, San Francisco, California, United States
  • Chen, Angel, Ultragenyx Pharmaceutical Inc., Novato, California, United States
  • Zhang, Lin, Ultragenyx Pharmaceutical Inc., Novato, California, United States
  • Roberts, Mary Scott, Ultragenyx Pharmaceutical Inc., Novato, California, United States
  • Portale, Anthony A., University of California, San Francisco, San Francisco, California, United States
Background

In patients with XLH, excess FGF23 induces hypophosphatemia, leading to musculoskeletal impairments. In two Phase 3 trials (NCT02526160, NCT02915705), burosumab significantly improved serum phosphorus concentrations in adults and children with XLH. We examined subject characteristics and long-term safety of burosumab by the absence or presence of nephrocalcinosis (NC) at baseline (BL) from these trials.

Methods

Adults were randomized (1:1) to burosumab 1.0 mg/kg every 4 weeks or placebo for 24 weeks; after 24 weeks, adults received burosumab through 96 weeks. Children were randomized (1:1) to burosumab 0.8 mg/kg every 2 weeks or oral phosphate and active vitamin D (Pi/D) for 64 weeks. NC was determined at BL and during study by ultrasound and graded by central readers from 0 (normal) to 4 (stone formation).

Results

In adults, NC was found in 73/134 patients (54%) at BL. Age, sex, and duration of treatment with Pi/D as adults did not differ by baseline NC group. Compared with adults without NC at BL, those with NC had longer duration of treatment with Pi during childhood (mean [SD] 13.2 [3.2] vs 11.3 [4.9] years) but not with D. After 96 weeks in adults, median 24-hr urine calcium increased by 35% overall but remained within the normal range. NC scores increased by +1 in 5/73 adults with NC at BL and 5/61 adults without NC at BL. In children, NC was found in 14/61 (23%) at BL. Compared with children without NC at BL, children with NC were older (7.6 [2.8] vs 5.7 [3.4] years), more likely to be male (71% vs 36%), treated longer with Pi/D pre-enrollment (4.8 [3.3] vs 3.6 [3.0] years), and had higher 24-hr urine calcium (4.4 [5.4] vs 2.3 [1.9] mg/kg/day [normal <4.0 mg/kg/day]). After 64 weeks in children, median urine calcium decreased by 50% overall. At week 64, NC scores did not increase in any child and decreased by 1 in 8 children. Serum creatinine and estimated GFR did not change in adults or children.

Conclusion

In adults with XLH, NC at BL was associated with longer duration of Pi during childhood. In children with XLH, NC was associated with longer duration of Pi and D pre-enrollment and with BL hypercalciuria. With long-term burosumab, the presence of NC at BL did not increase the risk of NC progression.

Funding

  • Commercial Support