Tenapanor relieves constipation in ESKD patients with hyperphosphataemia

Individuals with end-stage kidney disease (ESKD) who have mild-to-severe constipation obtain relief from tenapanor in the post hoc analysis of the phase III BLOCK study.

“[In this analysis,] the mean weekly stool frequency (WSF) increased, and the mean weekly stool consistency improved from constipation at baseline to normal in ESKD patients who were taking tenapanor to reduce serum phosphate,” said the researchers.

BLOCK included 219 patients with ESKD and hyperphosphataemia who were undergoing haemodialysis. The participants were randomized 1:1:1 to receive tenapanor 3, 10, or 30 mg BID for 8 weeks. Daily eDiary entries tracked stool frequency and consistency via the Bristol Stool Form Scale (BSFS).

This post hoc analysis included participants from the 8-week randomized treatment period (RTP) who had constipation (baseline WSF [BWSF] ≤6; n=59; mean age 53.5 years, 59.3 percent men) and severe constipation (BWSF ≤3; n=8; mean age 48.3 years, 87.5 percent men). Overall, the mean duration of dialysis treatment was 4.8 years, and the mean serum phosphate was 7.4 mg/dL. [ASN Kidney Week 2025, abstract TH-PO0223]

In patients with BWSF ≤6, the mean WSF increased from a mean of 4.7 at baseline to 8.2 during end-of-treatment (EOT) week of the RTP (mean change, 3.5; p<0.001). The mean weekly stool consistency score also increased from a mean BSFS of 2.7 to 4 between the two timepoints (mean change, 1.4; p<0.001).

These treatment effects were also observed in the BWSF ≤3 subgroup between baseline and EOT week of the RTP – from a mean WSF of 2.3 to 6.3 (mean change, 4; p<0.05) and a mean BSFS of 1.4 to 3.3 (mean change, 1.9; p=0.02).

Of note, the improvements in stool frequency and consistency were evident as early as week 1 and were sustained until end of RTP.

After the RTP, the reductions in mean serum phosphate were similar between the BWSF ≤6 and ≤3 subgroups (1 and 1.1 mg/dL, respectively). This aligned with the serum phosphate reductions reported in the overall cohort, the investigators noted.

The overall incidence of serious treatment-emergent adverse events (TEAEs) was 12 percent. The most common TEAE was diarrhoea (40.7 percent and 62.5 percent in the BWSF ≤6 and ≤3 subgroups, respectively).

The researchers acknowledged that the safety profile was consistent with that observed in the overall population.

Phosphate management critical in CKD patients

Constipation is common in ESKD patients on dialysis, which often impairs the effectiveness of peritoneal dialysis. [Kidney Int Rep 2019;5:121-134; Perit Dial Int 2019;39:399-404]

Tenapanor is a first-in-class, minimally absorbed inhibitor of sodium/hydrogen exchanger isoform 3, which reduces intestinal phosphate permeability through the paracellular pathway, the primary route of gastrointestinal phosphate absorption. [ACS Med Chem Lett 2022;13:1043-1051; Sci Transl Med 2018;10:eaam6474]

“Tenapanor is approved to reduce serum phosphorus in adults with chronic kidney disease (CKD) on dialysis as add-on therapy among those who have insufficient response to phosphate binders or who are intolerant of any dose of phosphate binder therapy,” the researchers said.

“Phosphate management is critical for CKD patients on dialysis, as failure to do so leads to a higher risk of comorbidities, death, and a potential delay in transplant waitlisting,” said Ardelyx Chief Medical Officer Dr Edward Conner, in a press release. “Our results show the [potential impact of tenapanor] in reducing serum phosphorus levels for these patients.”