Award: Outstanding Research Award in the Colon Category
Brian Lacy, MD, PhD, FACG1, Yang Yang, PhD2, David Rosenbaum, PhD2 1Mayo Clinic, Jacksonville, FL; 2Ardelyx, Inc., Waltham, MA
Introduction: Tenapanor (TEN) is a first-in-class, minimally systemic, inhibitor of intestinal sodium-hydrogen exchanger isoform 3 (NHE3) approved by the FDA for adults with irritable bowel syndrome with constipation (IBS-C). In multiple prospective, controlled clinical trials, tenapanor 50 mg bid significantly increased complete spontaneous bowel movements (CSBMs) in patients with IBS-C and reduced abdominal symptoms of pain and bloating relative to placebo. We conducted a post hoc analysis of pooled data from the phase 2b (NCT01923428) and phase 3 T3MPO-1 (NCT02621892) and T3MPO-2 (NCT02686138) studies to examine the time to onset of TEN effect on bowel function and abdominal symptoms in IBS-C.
Methods: Methods have been described previously for all studies. Patients (pts) were randomized to TEN 50 mg or placebo (PBO) bid for 12 or 26 weeks. A phone diary was used to collect data on daily CSBMs and abdominal symptoms (pain, bloating, and discomfort; each on a 0- to 10-point scale). Based on the pooled data within the first 12 weeks of the randomized treatment period in each of the 3 studies, the Kaplan-Meier method was used to analyze time to CSBM response (ie, achieving an increase of ≥1 in average weekly CSBMs), abdominal pain response and abdominal bloating response (ie, achieving a decrease of ≥30% in average weekly abdominal pain or abdominal bloating score).
Results: The pooled population included 1372 intent-to-treat pts (688 PBO, 684 TEN). Pt demographics were generally similar across the studies. For TEN-treated pts, the median time to CSBM response was 2 weeks; the estimated response probability was 52.3% by week 2, 72.5% by week 8 and 76.7% by week 12. The median time to abdominal pain response was 4 weeks; the estimated response probability was 54.6% by week 4, 67.9% by week 8 and 72.3% by week 12. The median time to abdominal bloating response was 5 weeks; the estimated response probability was 48.1% by week 4, 61.9% by week 8 and 67.7% by week 12.
Discussion: In this pooled analysis of three well-controlled studies, tenapanor exhibits a rapid onset of action with improvements in both bowel function and abdominal symptoms. Although onset of action occurs within the first week, continued therapy allows for a greater percentage of patients to achieve a meaningful response.
Figure: Figure. A, Time to CSBM Response (first 12 weeks). B, Weekly CSBM Response.
Yang Yang: Ardelyx, Inc. – Employee, Stock Options.
David Rosenbaum: Ardelyx, Inc. – Employee, Stock Options.
Brian Lacy, MD, PhD, FACG1, Yang Yang, PhD2, David Rosenbaum, PhD2, 13, Tenapanor Treatment Success for IBS-C Symptoms Increases with Duration of Therapy, ACG 2023 Annual Scientific Meeting Abstracts. Vancouver, BC, Canada: American College of Gastroenterology.
