Abstract: FR-PO163
Postprandial Serum Phosphorus and Calcium Concentrations in Adults and Children with X-Linked Hypophosphatemia (XLH) Are Within Normal Range During Burosumab Treatment
Session Information
- Bone and Mineral Metabolism: Phosphorus, FGF23, Vascular Calcification
November 08, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 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
- Imel, Erik, Indiana University School of Medicine, Indianapolis, Indiana, United States
- Jan de beur, Suzanne, John Hopkins University, Balitmore, Maryland, United States
- Munns, Craig, The Children''s Hospital at Westmead, Westmead, New South Wales, Australia
- Pitukcheewanont, Pisit, Ascendis Pharmaceutical, Palo Alto, California, United States
- San martin, Javier, ultragenyx, Novato, California, United States
- Insogna, Karl, Yale University, New Haven, Connecticut, United States
Background
In patients with XLH, excess FGF23 causes hypophosphatemia leading to musculoskeletal impairments. In Phase 3 trials (NCT02526160, NCT02915705), subcutaneous burosumab, 1 mg/kg every 4 weeks in adults or 0.8 mg/kg every 2 weeks in children, significantly improved fasting serum phosphorus (Pi) in subjects with XLH. Burosumab also improved fracture healing, stiffness, and physical function compared to placebo in adults; and rickets severity and growth compared to oral phosphate and active vitamin D in children. We evaluated the effect of burosumab on postprandial serum Pi and calcium in a sub-set of trial subjects.
Methods
Postprandial assessments were made in 26 adults and 13 children, 10-14 days after the prior dose of burosumab. Serum samples were obtained in the morning after an overnight fast. Subjects then consumed a typical phosphorus-containing breakfast, and samples were obtained 1 and 2 hours after breakfast. In adults, additional samples were obtained before and 1 and 2 hours after lunch.
Results
Adults (mean [SD] age 43 [12] years, 77% female, 89% white) and children (mean [SD] age 6 [3] years, 77% female, 92% white) had received burosumab for a mean of 24 and 15 months, respectively. At baseline, before any doses of burosumab, mean (SD) fasting serum Pi concentration was below the normal range (Table). After burosumab treatment, mean morning fasting Pi level increased significantly in each group. In adults, Pi levels decreased slightly if not significantly after breakfast, increased slightly before lunch, and remained stable 1 and 2 hours after lunch. In the children, serum Pi levels increased slightly if not significantly 1 and 2 hours after breakfast. Importantly, no subject had post-prandial hyperphosphatemia. There were no changes in serum calcium.
Conclusion
In adults and children with XLH receiving stable doses of burosumab, fasting and postprandial serum Pi and calcium concentrations are maintained within the normal range.
Serum Phosphorus mg/dL
| Subjects (Phosphorus Normal Range) | Pre-Burosumab | With Burosumab | |||||
| Before Breakfast | Before Breakfast | 1hr Post Breakfast | 2hr Post Breakfast | Before Lunch | 1hr Post Lunch | 2hr Post Lunch | |
| Adults (2.5-4.5 mg/dl) | 2.1 (0.4) | 3.1 (0.5) | 2.9 (0.6) | 2.8 (0.6) | 3.1 (0.5) | 3.2 (0.4) | 3.1 (0.5) |
| Children (3.2-6.1 mg/dl) | 2.3 (0.3) | 3.3 (0.5) | 3.3 (0.6) | 3.5 (0.5) | - | - | - |
Data are expressed as Mean (SD)