Discussing Safety, Tolerability of Tenapanor in Pediatric IBS-C patients, with Thomas Wallach, MD

At the 2025 North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN), held in Chicago, Illinois, investigators presented new interim safety findings from the phase 3 R-ALLY trial and its open-label extension evaluating tenapanor in pediatric patients with irritable bowel syndrome with constipation (IBS-C). Preliminary data demonstrated that tenapanor, a first-in-class sodium/hydrogen exchanger isoform 3 (NHE3) inhibitor, was safe and well-tolerated among adolescents, with no serious treatment-related adverse events reported.

“Tenapanor is a novel laxative that is generally thought to have some additional support for intestinal barrier function,” said Thomas Wallach, MD, Chief, Pediatric Gastroenterology, SUNY Downstate Health Sciences University, New York, New York. “It works by blocking something called NHE3, which allows... the colon to secrete more liquid into the intestine.”

The phase 3 R-ALLY study randomized 77 patients aged 12 to <18 years to receive tenapanor 25 mg twice daily, 50 mg twice daily, or placebo for 12 weeks. Fifty-six participants who completed the randomized treatment period entered a 40-week open-label extension. According to the study abstract, the authors noted that "In the OLE, no serious TEAEs were reported, all TEAEs were considered unrelated to study drug except diarrhea, and all TEAEs were resolved except 2 mild events: 1 overflow incontinence and 1 diarrhea."

“What we were very happy to report is that, with the exception of minor ones — like loose stool, which is not surprising with a laxative — there was really nothing that qualified as an adverse event or was jumping out, which is again consistent with the adult study,” Wallach said. “So this is highly reassuring and makes me comfortable, as a preliminary report, in using tenapanor in a pediatric population — because there is now safety data — and it also speaks to the likelihood that this will be nicely reported when the trial is complete.”

Wallach emphasized that while the abstract reports safety data, the question of efficacy remains under investigation.

“What I do think this [preliminary data] does allow is that if you are considering use because you are having a difficult situation and you want to consider additional options, I would feel comfortable using it based on the safety record. What I can’t say yet is that people should do this now, because we haven’t yet proven that it works. But I do think this is highly reassuring and highly suggestive.”

He added that the need for new constipation therapies remains significant in pediatrics.

“There is a huge need for volume-constrained, effective laxative therapy,” he said. “Constipation is a huge issue in this country. It drives a large amount of abdominal pain and can lead to complications that carry into adulthood. It drives secondary issues, like diverticula, when you’re older. It is a major problem.”

Reference:

Williams N, Wallach T, Ringheanu M, et al. SAFETY AND TOLERABILITY OF TENAPANOR IN PEDIATRIC PATIENTS WITH IRRITABLE BOWEL SYNDROME WITH CONSTIPATION: AN ANALYSIS OF BLINDED SAFETY DATA FROM A PHASE 3 STUDY AND ITS OPEN-LABEL EXTENSION. Abstract. Presented at: 2025 NASPGHAN Annual Meeting. November 5-9, 2025. Chicago, Illinois.