Tenapanor is a first-in-class, poorly absorbed, small-molecule inhibitor of the intestinal sodium/hydrogen exchanger isoform 3 (NHE3) that has been given the green light for the treatment of IBS-C in adults. The most current ROME IV diagnostic criteria acknowledge that functional constipation (FC) and IBS-C constitute a continuum of symptoms rather than being different entities. According to Wong, et al (AJG 2010), 89.5% of patients who satisfied the IBS-C criteria for ROME III also met the criterion for FC. The main objective for chronic idiopathic constipation (CIC) in individuals with IBS-C from the T3MPO-1 and T3MPO-2 phase 3 trials was used in a post hoc analysis to evaluate the effectiveness of tenapanor for FC.
Tenapanor 50 mg or a placebo was given twice daily to adult IBS-C (ROME III) patients who had undergone three complete spontaneous bowel movements (CSBM) in the previous week, ≤5 SBM in the previous week, and a weekly worst abdominal pain score of ≥3 (0–10 numerical rating scale) during a 2-week screening period. The regulatory endpoint for CIC, the durable responder rate, was calculated using information from the first 12 weeks of both studies. A patient is considered to be a durable responder if their weekly rise in CSBM is ≥1 from baseline and ≥3 from week to week during 9 of the study’s 12 weeks and 3 of the final 4 weeks.
The responder rate vs. placebo in the T3MPO-1 ITT group (tenapanor, n=307; placebo, n=299; mean age 45 years; 81% female) was 11.28% (adjusted relative risk 3.35; P<0.001). The responder rate vs. placebo in the T3MPO-2 ITT group (tenapanor, n=293, placebo, n=300; mean age 45 years; 82% female) was 15.49% (adjusted relative risk 3.75; P<0.001).
In general, tenapanor was well tolerated. The most typical adverse event was diarrhea, with severe diarrhea being observed in 2.5% of patients using tenapanor.
Tenapanor, with its new mode of action, offers promise as a viable treatment option for CIC, according to findings from the post hoc analysis of the T3MPO-1 and T3MPO-2 Phase 3 trials for IBS-C in adults. To support the findings, more clinical studies evaluating tenapanor in the CIC population were required.
Reference: eventscribe.net/2022/ACG-Posters/fsPopup.asp?PosterID=514125&mode=posterinfo
