Tenapanor showed more positive results in its second pivotal phase 3 trial for constipation-predominant irritable bowel syndrome, which the manufacturer Ardelyx said will support a new drug application next year.
The small-molecule NHE3 inhibitor, which works by increasing sodium in the gut, showed a better combined responder rate in the T3MPO-2 trial relative to the previous T3MPO-1 trial, meeting its primary endpoint and all secondary endpoints.
“These results are a game-changer for patients with IBS-C, their treating physicians and for Ardelyx as a company,” Mike Raab, president and CEO of Ardelyx, said in a press release. “They demonstrate the significant benefit tenapanor can have for patients with IBS-C, importantly, leading to a normalization of bowel movements for many patients. These results show that tenapanor has significant potential in the market and bolsters our commitment to identify the ideal collaboration partner to help ensure that we reach the most patients possible who would benefit from therapy.”
In the double-blind, multicenter trial, investigators randomly assigned 593 patients with active IBS-C to receive 50 mg tenapanor or placebo twice per day for 26 weeks.
The combined responder rate served as the primary endpoint, and was defined as a 30% reduction in abdominal pain and an increase of at least one complete spontaneous bowel movement (CSBM) in the same week for at least half of the 12 weeks in the treatment period.
A significantly greater percentage of patients treated with tenapanor achieved the primary endpoint (36.5% vs. 23.7%; P < .001).
Further, CSBM and abdominal pain responder rates were significantly greater in the treatment group for both 6 and 9 of the 12 treatment weeks, and there was a consistent response across the whole study period.
The drug was also well-tolerated, and the most common adverse events included diarrhea (16% vs. 3.7% with placebo), flatulence (3.1% vs. 1%), nasopharyngitis (4.4% vs. 3.7%) and abdominal distension (3.4% vs. 0.3%).
“The placebo adjusted discontinuation rate due to diarrhea was 5.8%,” according to the press release.
The company said the results from the two T3MPO trials should support an NDA submission in the second half of 2018, and it plans to present detailed data at a scientific meeting next year.
Patients who completed the trials are eligible to enter the open-label, long-term T3MPO-3 safety trial, in which they can continue taking tenapanor for up to a year. This trial has achieved full enrollment and the company expects it to be completed later this year, and the results will be included in the NDA submission.
“IBS-C is a highly burdensome and difficult-to-treat condition affecting more than 11 million people in the United States, and often preventing them from engaging in day-to-day activities, such as going to work, exercising and even meeting socially with family and friends,” William Chey, MD, of University of Michigan, said in the press release. “Based on tenapanor’s unique mechanism of action, which relies upon the inhibition of sodium absorption, and the exciting data reported today, tenapanor has the potential to be an important advancement and a new treatment option for patients suffering from IBS-C.”
Ardelyx is also evaluating tenapanor in a phase 3 trial for hyperphosphatemia in patients with end-stage renal disease who are on dialysis, per the press release.
Disclosures: Chey reports he is a consultant for Ardelyx, and Raab is employed by Ardelyx.