Tenapanor Provides Varied Timing for IBS-C Symptom Relief


Investigator Brian E. Lacy, MD, PhD discusses new post hoc analysis that he hopes will provided clearer expectations for timing of benefit with tenapanor.

Tenapanor provides complete spontaneous bowel movement response in treated patients in a median of 2 weeks, according to new findings from a pooled analysis of 3 controlled trials assessing the drug in patients with irritable bowel syndrome with constipation (IBS-C).

In a post hoc analysis of data from a phase 2b and a pair of phase 3 trials, presented at the American College of Gastroenterology (ACG) 2023 Annual Scientific Meeting this week in Vancouver, BC, a team of US investigators reported that tenapanor provided a rapid onset of action in patients with IBS-C. The team additionally reported the intestinal sodium-hydrogen exchanger isoform 3 (NHE3) inhibitor was associated with improved bowel function and abdominal symptoms.

Led by Brian E. Lacy, MD, PhD, of the Mayo Clinic in Jacksonville, investigators assessed pooled data from the phase 2b and 3 T3MPO-1 and T3MPO-2 trials to assess the the time to onset of effect with twice-daily tenapanor 50 mg on bowel function and abdominal symptoms in patients with IBS-C.

Across the 1372 intent-to-treat patients—of whom 684 received tenapanor and 688 received placebo—Lacy and colleagues observed a median time of 2 weeks to complete spontaneous bowel movement response in treated patients. The probability of estimated response to therapy was 52.3% by week 2—then increasingly greater through weeks 8 (72.5%) and 12 (76.7%).

Additionally, they reported a median time of 4 weeks to abdominal pain response in tenapanor-treated patients with IBS-C; again, the probability of estimated response increased gradually from week 4 (54.6%) to week 12 (72.3%).

Response to abdominal bloating was reportedly less frequent, and longer in onset; median time was 5 weeks, and estimated response probably was 48.1% at week 4 and 67.7% at week 12.

In an interview with HCPLive at ACG 2023, Lacy discussed the unique mechanism of action of tenapanor, relative to other medications approved by the US Food and Drug Administration (FDA) for patients with IBS-C.

“By inhibiting that (NHE3) receptor, sodium is retained within the lumen of the GI tract,” Lacy said. “That pulls water into the GI tract, and that softens stool and increases GI transit, leading to an improvement in symptoms of IBS and constipation—meaning constipation symptoms, but also symptoms of abdominal pain and bloating.”

While the understood mechanism of action and late-stage evidence of the drug is highly supportive of its use in treating IBS-C, questions have remained about its timeliness in resolving unique symptoms. The takeaway from his team’s research, Lacy said, is that providers “shouldn’t give up too early.”

“Although most patients responded for constipation symptoms in 2 weeks, waiting a little bit longer means you'll get more patients who respond,” Lacy said. “Importantly, the cardinal symptom, as all of our listeners probably know, for IBS is abdominal pain or discomfort. And so abdominal pain and discomfort responded within about 4 weeks. So that's a little bit later than the constipation symptoms.”

Lacy stressed the nature of patients wanting assurance of timing with their new medication—regardless of how long they’ve been burdened with their disease and what other treatments they have tried. The tradeoff of certainty versus expediency may better help patients see a regimen through.

“I think it will provide information to providers and patients about expectations,” Lacy said. “If a patient comes in, they meet ROME IV criteria, they have symptoms of IBS with constipation, you can confidently say, 'Mrs. Jones, your constipation symptoms will likely respond within the first 2 weeks, but don't be surprised that the abdominal pain component may take a little bit longer, so don't be disappointed and don't give up too early.’”


Lacy BE, Yang Y, Rosenbaum D. 13 - Tenapanor Treatment Success for IBS-C Symptoms Increases with Duration of Therapy. Paper presented at: ACG 2023 Annual Scientific Meeting. Vancouver, BC, Canada. October 20 – 25, 2023.

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