Abstract: TH-PO163
The Predictive Value of Early Response to Tenapanor for the Treatment of Hyperphosphatemia in Patients Receiving Maintenance Dialysis
Session Information
- CKD-MBD: Targets and Outcomes
November 03, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Bone and Mineral Metabolism
- 402 Bone and Mineral Metabolism: Clinical
Authors
- Weiner, Daniel E., Tufts University School of Medicine, Boston, Massachusetts, United States
- Spiegel, David M., Ardelyx, Inc., Waltham, Massachusetts, United States
- Yang, Yang, Ardelyx, Inc., Waltham, Massachusetts, United States
- Rosenbaum, David P., Ardelyx, Inc., Waltham, Massachusetts, United States
Background
Serum phosphorus (sP) control remains challenging for patients receiving maintenance dialysis. Despite adequate dialysis, dietary counseling, and use of phosphate binders, many patients fail to achieve and maintain target sP. Tenapanor is an investigational phosphate absorption inhibitor (PAI) dosed twice a day that blocks the paracellular absorption of dietary phosphate in the intestine. This post hoc analysis of the phase 3 PHREEDOM (NCT03427125) study evaluated whether an early sP reduction predicts continued sP control at week 12 and end of treatment.
Methods
In PHREEDOM, patients receiving maintenance dialysis with hyperphosphatemia were randomized 3:1 to tenapanor 30 mg twice a day or sevelamer. Early responders were defined as those with ≥2 of 3 sP measurements with a reduction of ≥1.2 mg/dL from baseline at weeks 1, 2, and 4. Early responders were assessed for continued response at week 12 (single measurement) and weeks 17, 22, and 26 defined as having sP ≥1.2 mg/dL lower than baseline at week 12 or ≥1.2 mg/dL lower than baseline for ≥2 of 3 sP measurements at weeks 17, 22, and 26 (end of treatment).
Continued response rates were estimated using 2 approaches: Conservative – early responders who missed sP measurement at week 12 or missed ≥2 of 3 sP measurements at weeks 17, 22, and 26 were considered late non-responders; Observed Case – only the early responders who remained on treatment with sP measurement at week 12 or with ≥2 of 3 sP measurements at weeks 17, 22, and 26 were included in analysis.
Results
In PHREEDOM, 46.4% (189/407) of tenapanor-treated patients achieved an early response. The Table shows the proportion of early responders who remained responders at week 12 and end of treatment. Most early non-responders remained non-responders throughout the study.
Conclusion
Among patients receiving maintenance dialysis with an early response to tenapanor who remained on treatment, ≈70% maintained their response at week 12 and ≈80% continued to have a clinically meaningful therapeutic response at the end of treatment. This approach could help guide real-world clinical practice.
| Early Responders Who Achieved a Decrease in sP of ≥1.2 mg/dL at Week 12 and ≥2 of 3 Visits at the End of the 26-Week Treatment Period | ||
| Week 12 | End of treatment | |
| Conservative approach | 57.1% (108/189) | 58.2% (110/189) |
| Observed case approach | 68.8% (108/157) | 79.1% (110/139) |
Funding
- Commercial Support –