Tenapanor Improves Abdominal Symptoms Independent of Bowel Symptoms in IBS-C

Tenapanor (Ibsrela) improves abdominal symptoms irrespective of changes in complete spontaneous bowel movement (CSBM) frequency in adults with irritable bowel syndrome with constipation (IBS-C), according to findings from a recent study.1

The post hoc analysis examined data derived from a phase 2b study and 2 phase 3 studies, T3MPO-1 and T3MPO-2, of tenapanor for the treatment of IBS-C and found the first-in-class, minimally absorbed intestinal sodium/hydrogen exchanger isoform 3 inhibitor improved abdominal symptoms independent of bowel symptoms.1

The US Food and Drug Administration approved tenapanor for the treatment of adult patients with IBS-C on September 12, 2019, based on data from the phase 3 T3MPO-1 and T3MPO-2 studies demonstrating greater treatment response, including an increase in weekly average CSBMs and reduced weekly average abdominal symptoms, with tenapanor than with placebo.2

“In a phase 2b and two phase 3 studies, T3MPO-1 and T3MPO-2, tenapanor 50 mg twice a day (bid) significantly increased complete spontaneous bowel movements and reduced abdominal symptoms compared with placebo,” Darren Brenner, MD, a professor of gastroenterology and hepatology and a gastroenterologist at Northwestern Feinberg School of Medicine, and colleagues wrote.1 “The relationship between these improvements in abdominal symptoms and bowel movements remains undetermined.”

To address this gap in research, investigators examined data from each of these studies for participants who received tenapanor 50 mg or placebo and had no CSBMs in ≥ 6 of the first 12 weeks of treatment. Investigators defined a CSBM as a spontaneous bowel movement occurring without the use of a rescue medication within 24 hours for which the subject indicated they felt like they completely emptied their bowels.1

Patients reported daily assessments for abdominal pain, bloating, and discomfort on an 11-point scale through an interactive voice response system telephone diary, where 0 represented no abdominal symptoms and 10 represented very severe abdominal symptoms. Changes from baseline in weekly abdominal symptom scores and the 3-item Abdominal Score (AS3) were analyzed to determine abdominal symptom response in tenapanor relative to placebo.1

The pooled safety analysis set included 1382 patients (tenapanor, n = 691; placebo, n = 691). In total, 641 patients were classified as meeting the criteria for the no-CSBM group and 640 (tenapanor, n = 275; placebo, n = 365) were included in the pooled intention-to-treat (ITT) efficacy analysis.1

In the no-CSBM subgroup, investigators noted tenapanor-treated patients experienced a greater mean reduction from baseline in AS3 than placebo-treated patients at week 12 (least squares mean [LSM] change, −1.74 vs −1.29; LSM difference, −0.45; P = .007). Additionally, in this group, the weekly AS3 response rate at week 12 was 40.2% in tenapanor-treated patients compared with 29.6% in placebo-treated patients (P = .008).1

Investigators observed similar improvements across individual abdominal symptom scores. Specifically, the weekly abdominal pain response rate at week 12 was 42.3% in tenapanor-treated patients compared with 32.1% in placebo-treated patients (P = .013), and reductions were also observed from baseline in the weekly bloating and discomfort symptom scores for no-CSBM patients at week 12 (LSM difference, −0.45; P = .008 and LSM difference, −0.46; P = .009, respectively).1

The pooled safety analysis set included 1382 patients (tenapanor, n = 691; placebo, n = 691). Among the no-CSBM subgroup in the pooled safety analysis set (n = 641), the most common treatment-emergent adverse events were diarrhea (tenapanor, 6.9% vs placebo, 1.1%), nasopharyngitis (4.0% vs 3.0%), urinary tract infection (2.5% vs 2.2%), and flatulence (2.2% vs 1.9%).1

Investigators acknowledged multiple limitations to these findings, including the stringent criteria used to enroll patients with IBS-C in the trials that may not reflect the real-world disease population as well as the lack of consideration of quality of life with tenapanor.1

“This post hoc analysis demonstrates that tenapanor is effective in reducing both abdominal and bowel symptoms in adults with IBS-C,” investigators concluded.1 “The decrease in abdominal pain and associated abdominal symptoms in these clinical trials appears to be separate from bowel symptoms and may be attributable to tenapanor’s additional mechanisms of action.”

References

1. Brenner DM, Sayuk GS, Cash BD, et al. Tenapanor Improves Abdominal Symptoms Irrespective of Changes In Complete Spontaneous Bowel Movement Frequency in Adults With Irritable Bowel Syndrome With Constipation. Dig Dis 2024; https://doi.org/10.1159/000543166
2. Ardelyx. Ardelyx Receives FDA Approval for IBSRELA® (Tenapanor), an NHE3 Sodium Transport Inhibitor, for the Treatment of Irritable Bowel Syndrome with Constipation. September 12, 2019. Accessed December 23, 2024. https://ir.ardelyx.com/news-releases/news-release-details/ardelyx-receives-fda-approval-ibsrelar-tenapanor-nhe3-sodium