C0268 - Efficacy of Tenapanor in Improving IBS-C Abdominal Symptoms: A Post Hoc Analysis of Multi-Item Abdominal Score From the 26-Week Phase 3 T3MPO-2 Study

Monday, October 24, 2022

3:00 PM – 5:00 PM ET

Location: Crown Ballroom

Has Audio

Presenting Author(s)

AL

Anthony Lembo, MD, FACG

Beth Israel Deaconess Medical Center and Harvard Medical School
Boston, Massachusetts

Anthony Lembo, MD, FACG¹, William D. Chey, MD², Susan Edelstein, PhD³, Yang Yang, PhD³, David M. Spiegel, MD³, David P. Rosenbaum, PhD³
¹Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA; ²Michigan Medicine, Ann Arbor, MI; ³Ardelyx, Inc., Waltham, MA

Introduction: Tenapanor is a minimally absorbed, small-molecule inhibitor of intestinal sodium/hydrogen exchanger 3 (NHE3), approved for the treatment of irritable bowel syndrome with constipation (IBS-C). Preclinical studies demonstrated that tenapanor reduced intestinal permeability, inhibited TRPV1 signaling, and was associated with reduced visceral hypersensitivity and abdominal pain. Here we investigate the effects of tenapanor on multi-item abdominal score using data from T3MPO-2 (NCT02686138), a long-term phase 3 study of tenapanor.

Methods: Patients with IBS-C with < 3 weekly complete spontaneous bowel movements and weekly abdominal pain score ≥3 (0-10 scale) during a 2-week screening period were randomized to tenapanor 50 mg or placebo twice a day in a 26-week randomized treatment period (RTP). Patients rated 5 abdominal symptoms on an 11-point scale (0=no symptom to 10=worst possible symptom) using an eDiary.

The abdominal score 3 (AS3) is the mean of weekly scores for abdominal pain, discomfort, and bloating. The abdominal score 5 (AS5) is the mean of weekly scores for abdominal pain, discomfort, bloating, fullness, and cramping. The overall change from baseline (CFB) in the 26-week RTP and week 26 CFB in AS3 and AS5 were compared between arms using mixed-effects models with repeated measures. The cumulative distribution of CFB in AS3 or AS5 at week 26 was compared along with the Wilcoxon rank sum test. The 13/26-week AS3 or AS5 response, defined as achieving a reduction of ≥2 points in AS3 or AS5 for ≥13 weeks of the 26-week RTP, was compared using the Pearson’s chi-square test.

Results: T3MPO-2 randomized 620 patients. In the intent-to-treat analysis set (tenapanor, n=293; placebo, n=300), the tenapanor arm had greater mean reduction in AS3 than placebo over the 26-week RTP (Figure a; −2.74 vs −2.15, P=0.0001) and in week 26 (−3.27 vs −2.60, P=0.0007). At week 26, cumulative distribution of CFB significantly favored tenapanor over placebo (P=0.0094). The tenapanor arm also had a higher 13/26-week AS3 response rate than placebo (46.4% vs 35.7%, P=0.0078). For AS5, mean CFB (Figure b; P=0.0001), distribution of CFB at week 26 (P=0.0121), and 13/26-week response rate (P=0.0015) were similarly improved with tenapanor.

Discussion: Few treatments for IBS-C improve abdominal pain, discomfort, or bloating. This post hoc analysis demonstrates that tenapanor significantly improves IBS-C–associated abdominal symptoms with an early onset of action that is sustained throughout the treatment period.

Figure: Figure. Treatment with tenapanor resulted in a greater and sustained reduction from baseline in combined abdominal symptom scores over the 26-week treatment period vs placebo.
Error bars represent standard error.
AS3, abdominal score 3; AS5, abdominal score 5; bid, twice a day; BL, baseline; CFB, change from baseline; LS, least squares.

Disclosures:

Anthony Lembo: Alkermes – Consultant. Arena Pharmaceuticals, Inc. – Consultant. Bayer – Consultant. Bristol-Myers Squibb – Stock Options. Gemelli Biotech – Consultant. Ironwood Pharmaceuticals, Inc. – Consultant. Johnson & Johnson – Stock Options. OrphoMed, Inc. – Consultant. Salix Pharmaceuticals, Inc. – Consultant. Shire, a Takeda company – Consultant. Takeda Pharmaceuticals – Consultant. Vibrant – Advisor or Review Panel Member. Vibrant Pharma Inc. – Consultant.

William Chey: Abbvie – Consultant. Allakos – Consultant. Alnylam – Consultant. Arena – Consultant. Biomerica – Consultant. Commonwealth Diagnostics International – Consultant. Gemelli – Consultant. GI OnDEMAND – Stock Options. Ironwood – Consultant. Isothrive – Consultant. Isothrive – Stock Options. Modify Health – Stock Options. Nestle – Consultant. Phathom – Consultant. Progenity – Consultant. QOL Medical – Consultant, Grant/Research Support. Redhill – Consultant. Salix – Consultant, Grant/Research Support. Urovant – Consultant. Vibrant – Consultant.

Susan Edelstein: Ardelyx, Inc. – Employee.

Yang Yang: Ardelyx, Inc. – Employee.

David Spiegel: Ardelyx, Inc. – Employee.

David Rosenbaum: Ardelyx, Inc. – Employee.

Anthony Lembo, MD, FACG¹, William D. Chey, MD², Susan Edelstein, PhD³, Yang Yang, PhD³, David M. Spiegel, MD³, David P. Rosenbaum, PhD³. C0268 - Efficacy of Tenapanor in Improving IBS-C Abdominal Symptoms: A Post Hoc Analysis of Multi-Item Abdominal Score From the 26-Week Phase 3 T3MPO-2 Study, ACG 2022 Annual Scientific Meeting Abstracts. Charlotte, NC: American College of Gastroenterology.