Abstract: TH-PO164
Sustained Phosphate Reduction Assessed by Phosphate Area under the Curve with Tenapanor Is Associated with Reduced Fibroblast Growth Factor 23 in Patients with CKD and Hyperphosphatemia on Dialysis
Session Information
- CKD-MBD: Clinical
October 24, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Bone and Mineral Metabolism
- 502 Bone and Mineral Metabolism: Clinical
Authors
- Martin, Kevin J., Saint Louis University School of Medicine, St Louis, Missouri, United States
- Higgins, Simon, Ardelyx Inc, Waltham, Massachusetts, United States
- Yang, Yang, Ardelyx Inc, Waltham, Massachusetts, United States
- Rosenbaum, David P., Ardelyx Inc, Waltham, Massachusetts, United States
- Spiegel, David M., Ardelyx Inc, Waltham, Massachusetts, United States
Background
The 2017 KDIGO CKD-MBD guidelines recommend that strategies for managing hyperphosphatemia (HP) be based on the use of serial measurements. Average phosphate (P) area under the curve (AUC) has been identified as a stronger predictor of outcomes than other P estimates. Intact fibroblast growth factor 23 (iFGF23) is elevated in end-stage kidney disease and is associated with increased cardiovascular mortality, but is often not well correlated to single-point estimates of P. Tenapanor (TEN) is approved to reduce serum P in adults with CKD as add-on therapy in patients (pts) who have an inadequate response to P binders (PBs) or who are intolerant of any dose of PBs. We used P AUC to assess whether better long-term P control with TEN is associated with lower iFGF23.
Methods
In a secondary analysis of the Ardelyx-supported PHREEDOM study, a 52-week, phase 3 trial of TEN as a monotherapy for HP in adults on maintenance dialysis, pts with P ≥6.0 and ≤10.0 mg/dL and a P increase ≥1.5 mg/dL after PB washout were treated for 26 weeks with TEN 30 mg bid during an open-label randomized treatment period (RTP). Correlation analyses between average daily P AUC above 4.5 mg/dL over the RTP and iFGF23 at the end of the RTP were performed along with summaries of changes in iFGF23 by P AUC categories.
Results
In the full analysis set (n=407), TEN reduced P by 1.3 (SD: 1.8) mg/dL on average at the end of the RTP. Median iFGF23 was reduced from 6417.5 pg/mL at baseline to 5051.6 pg/mL at the end of the RTP (median percent change: −23.2%). There was a positive correlation between average daily P AUC and iFGF23 (ρ=0.499, P<0.001). A trend of higher median iFGF23 was seen across categories of P AUC. Greater percent reductions from baseline in iFGF23 were seen in P AUC categories representative of better P control than categories representative of worse control (Table).
Conclusion
Improved P control with TEN, as measured by P AUC, was associated with lower iFGF23.
iFGF23 at Week 26 and Change From Baseline (CFB) by P AUC Category Above 4.5 mg/dL
| P AUC category: >0–0.5 mg/dL | P AUC category: >0.5–1 mg/dL | P AUC category: >1–2 mg/dL | P AUC category: >2 mg/dL | |
| iFGF23 at Week 26, median | 623 pg/mL | 2450 pg/mL | 4127 pg/mL | 10866 pg/mL |
| iFGF23 CFB, % | −36% | −48% | −19% | −12% |
Funding
- Commercial Support – Ardelyx, Inc.