FDA NewsPerspective

FDA approves Ibsrela for IBS-C in adults

The FDA on Thursday approved Ibsrela, a 50 mg, twice-daily oral therapy for irritable bowel syndrome with constipation in adults.

“Ibsrela has the potential to provide IBS-C patients and their doctors with a novel mechanism and an innovative approach to managing IBS-C, a highly burdensome and difficult-to-treat condition affecting more than 11 million people in the United States,” Mike Raab, president and CEO of Ardelyx, said in a company-issued press release.

The approval of tenapanor (Ibsrela, Ardelyx) — a minimally absorbed small molecule that acts locally in the gastrointestinal tract to inhibit the sodium-hydrogen exchanger NHE3 — is based on data from two phase 3, randomized, double-blind, placebo-controlled trials.

Both trials were identical through the initial 12 weeks of therapy. One of the trials continued for an additional 14 weeks of treatment, whereas the other trial included a 4-week randomized withdrawal period.

Proportion of patients who responded to the therapy during the 12-week treatment period served as the primary endpoint. A patient was considered a responder if they experienced at least a 30% reduction in weekly average abdominal pain score compared with baseline and an increase of at least one complete spontaneous bowel movement in weekly average from baseline, in the same week, for at least 6 of the first 12 treatment weeks.

In the first trial, 37% of patients receiving tenapanor met the primary endpoint compared with 24% of patients receiving placebo. Twenty-seven percent of patients receiving tenapanor in the second trial met the primary endpoint compared with 19% of patients receiving placebo.

The most common adverse event in both studies was diarrhea — 16% with tenapanor vs. 4% with placebo in trial 1, 15% with tenapanor vs. 2% with placebo in trial 2.

Tenapanor is contraindicated in patients younger than 6 years. The safety and efficacy of tenapanor in patients younger than 18 years has not yet been established.

The contraindication is based on a study of young juvenile rats, which demonstrated that tenapanor caused death presumed to be due to dehydration, according to the release.

The FDA on Thursday approved Ibsrela, a 50 mg, twice-daily oral therapy for irritable bowel syndrome with constipation in adults.

“Ibsrela has the potential to provide IBS-C patients and their doctors with a novel mechanism and an innovative approach to managing IBS-C, a highly burdensome and difficult-to-treat condition affecting more than 11 million people in the United States,” Mike Raab, president and CEO of Ardelyx, said in a company-issued press release.

The approval of tenapanor (Ibsrela, Ardelyx) — a minimally absorbed small molecule that acts locally in the gastrointestinal tract to inhibit the sodium-hydrogen exchanger NHE3 — is based on data from two phase 3, randomized, double-blind, placebo-controlled trials.

Both trials were identical through the initial 12 weeks of therapy. One of the trials continued for an additional 14 weeks of treatment, whereas the other trial included a 4-week randomized withdrawal period.

Proportion of patients who responded to the therapy during the 12-week treatment period served as the primary endpoint. A patient was considered a responder if they experienced at least a 30% reduction in weekly average abdominal pain score compared with baseline and an increase of at least one complete spontaneous bowel movement in weekly average from baseline, in the same week, for at least 6 of the first 12 treatment weeks.

In the first trial, 37% of patients receiving tenapanor met the primary endpoint compared with 24% of patients receiving placebo. Twenty-seven percent of patients receiving tenapanor in the second trial met the primary endpoint compared with 19% of patients receiving placebo.

The most common adverse event in both studies was diarrhea — 16% with tenapanor vs. 4% with placebo in trial 1, 15% with tenapanor vs. 2% with placebo in trial 2.

Tenapanor is contraindicated in patients younger than 6 years. The safety and efficacy of tenapanor in patients younger than 18 years has not yet been established.

The contraindication is based on a study of young juvenile rats, which demonstrated that tenapanor caused death presumed to be due to dehydration, according to the release.

    Perspective
    Dmitriy Kedrin

    Dmitriy Kedrin

    Constipation is a fairly common diagnosis encountered in a gastroenterology clinic, and while there are many lifestyle changes as well as simple over-the-counter agents that can be recommended, for some patients this just does not work. When it comes to medication options used to treat constipation, what most patients care about is reduction in pain, as well as having more regular bowel movements. Our understanding of general bowel physiology led to a development of several blockbuster drugs, so when a new medication, especially with a different mechanism of action enters the scene, people take notice.

    The FDA recently approved tenapanor (Ibsrela, Ardelyx) for the treatment of constipation predominant IBS (IBS-C). The treatment acts by locally inhibiting the sodium hydrogen exchanger 3 (NHE3) in the gut. The drug is also used in patients with chronic kidney disease on dialysis to cause a reduction in serum phosphorus. The FDA approval was based on two clinical trials of patients who met Rome III criteria for IBS-C, related to abdominal pain and bowel movement frequency.

    For those wondering what happened to the phosphorus concentrations in the patients receiving tenapanor, in the two studies, the changes in serum phosphorus and sodium were not considered clinically meaningful, and none were reported as adverse events. So it was not at all surprising to find that the most common side effect after receiving tenapanor was diarrhea (16% with tenapanor vs. 4% with placebo in first trial and 15% with tenapanor vs. 2% with placebo in the second).

    Unclear how clinically relevant this will be on the whole, but 2.5% of patients reported severe diarrhea. I am optimistic due to the novelty of the mechanism of action and gut-specificity of this new agent. I am also optimistic that the treatment addresses the two main symptoms that patients seek relief from – pain and frequency of bowel movements. It remains to be seen how cost-effective and well tolerated this medication will be with long-term use.

    • Dmitriy Kedrin, MD, PhD
    • Elliot Hospital

    Disclosures: Kedrin runs a literature review podcast and reports no relevant financial disclosures.