FDA approves new treatment of Irritable Bowel Syndrome with Constipation

Food and Drug Administration has approved a new drug to treat irritable bowel syndrome with constipation (IBS-C) called tenapanor (IBSRELA). The 50 mg, a twice daily oral pill is supposed to increase bowel movements and decrease abdominal pain for IBS-C patients.

Ardelyx a specialized biopharmaceutical company has received approval for manufacture of the drug from Food and Drug Administration.IBSRELA is a minimally-absorbed small molecule that acts locally in the gastrointestinal (GI) tract to inhibit the sodium-hydrogen exchanger NHE3, resulting in an increase in bowel movements and a decrease in abdominal pain for IBS-C patients.

"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," commented Mike Raab, president and chief executive officer of Ardelyx. "This approval is an extremely important and rewarding milestone for Ardelyx and represents the culmination of years of dedication to advancing our discoveries and medicines in an effective and rigorous manner. We look forward to establishing a commercial collaboration with a partner that has the capabilities to drive the successful launch and marketing of IBSRELA in this large and underserved IBS-C patient population."

Mr. Raab continued, "With the approval of IBSRELA for IBS-C, along with the successful completion of our AMPLIFY trial in hyperphosphatemia, we've delivered on two major corporate milestones in the last two weeks due to flawless execution by the remarkable and talented team at Ardelyx. With these milestones accomplished, and the PHREEDOM trial reading out in Q4, I have great confidence that we are well-positioned to file our NDA for hyperphosphatemia next year with potential approval and launch in 2021. We are excited about this next chapter for Ardelyx as we begin the development of our playbook for launch and commercialization of tenapanor for hyperphosphatemia in chronic kidney disease patients on dialysis and are excited to begin sharing more of our vision in the coming months."

The Phase 3 IBS-C program included two randomized, double-blind, placebo-controlled trials. The trial designs were identical through the first 12 weeks of treatment, and thereafter differed in that Trial 1 (NCT02686138) continued for an additional 14 weeks of treatment (26 weeks double-blind treatment), whereas Trial 2 (NCT02621892) included a 4-week randomized withdrawal (RW) period (12 weeks double-blind treatment). Patients who were enrolled in these trials met the Rome III criteria for IBS-C, related to abdominal pain and bowel movement frequency.

Primary Endpoint

The primary endpoint for both trials was the proportion of patients who were responders during the 12-week treatment period. A responder, as defined by the FDA, was a patient who experienced at least a 30% reduction in the weekly average abdominal pain score compared with baseline and an increase of at least 1 complete spontaneous bowel movement (CSBM) in weekly average from baseline, in the same week, for at least 6 of the first 12 treatment weeks.

Results

In both Phase 3 IBS-C trials, IBSRELA met the primary endpoint as compared with placebo (Trial 1: 37% versus 24%, IBSRELA versus placebo, respectively. Trial 2: 27% versus 19% IBSRELA versus placebo, respectively).

In Trials 1 and 2, the proportion of responders for 9 out of the first 12 weeks, including at least 3 of the last 4 weeks, was greater in IBSRELA-treated patients compared to placebo-treated patients. In addition, in Trial 1, the proportion of responders for 13 out of 26 weeks was greater in IBSRELA‑treated patients compared to placebo-treated patients. In both trials, improvements from baseline in average weekly CSBMs and abdominal pain were observed by Week 1, with improvement maintained through the end of treatment.

In both studies, the most common adverse event was diarrhea (16% with IBSRELA vs 4% with placebo in Trial 1; and 15% with IBSRELA vs 2% with placebo in Trial 2), with severe diarrhea reported in 2.5% of IBSRELA-treated patients compared to 0.2% on placebo‑treated patients during the 26 weeks of Trial 1 and the 12 weeks of Trial 2. Overall discontinuation rates were low among patients treated with IBSRELA (7.6%) and placebo (0.8%) and the most common adverse reaction leading to discontinuation was diarrhea (6.5% of IBSRELA-treated patients compared to 0.7% of placebo-treated patients).

Indications and Usage

IBSRELA (tenapanor) is indicated for treatment of irritable bowel syndrome with constipation (IBS-C) in adults.