Ardelyx reported positive data from the first of two Phase III studies evaluating its lead oral sodium–hydrogen exchanger 3 (NHE3) inhibitor tenapanor in patients with irritable bowel syndrome with constipation (IBS-C). The 12-week, placebo-controlled T3MPO-1 trial met its primary combined responder rate endpoint, with 27% of tenapanor-treated patients, compared with 18.7% of placebo-treated patients, achieving at least a 30% reduction in abdominal pain and an increase of one or more complete spontaneous bowel movements (CSBM) in the same week for at least 6 of the 12 weeks of treatment. The study also met seven of eight secondary endpoints.
“We're pleased to have achieved the primary endpoint in the T3MPO-1 trial,” said Mike Raab, president and CEO at Ardelyx. “In this trial, tenapanor demonstrated clinical activity across a large number of study parameters and had a favorable safety profile consistent with previous clinical experience. With a differentiated mechanism of action, we believe tenapanor has the potential to augment the care of patients with IBS-C.”
“The individual CSBM responder rate from the 6 of 12 week analysis was the one secondary endpoint not met, and those data are not consistent with the results from our previous clinical studies,” added David Rosenbaum, Ph.D., chief development officer at Ardelyx. “We plan to assess these data alongside the results from T3MPO-2, our 6-month Phase III study, to evaluate the total benefit that tenapanor may provide to patients with this extremely challenging condition.”
Ardelyx said data from T3MPO-2 are expected during Q4 2017. Eligible patients from T3MPO-2 can then continue to receive tenapanor for up to a year as part of the open-label, long-term safety T3MPO-3 study.
The firm is developing a pipeline of gut-restricted drugs for treating cardiorenal and gastrointestinal indications. The firm’s gastrointestinal portfolio includes RDX8940, a TGR5, or Takeda-G-protein-receptor-5, agonist that the firm says is nearing Phase I development. Tenapanor also heads the Ardelyx cardiorenal pipeline and is in Phase III development for treating hyperphosphatemia in patients with end-stage renal disease who are on dialysis. Positive data from the first Phase III study were reported in February.
Ardelyx's second late-clinical cardiorenal pipeline candidate RDX7675 is a Phase III-stage oral, nonabsorbed potassium-binding polymer in development for the potential treatment of hyperkalemia. A Phase III study and an onset-of-action trial were initiated in January.
Tenapanor was originally discovered by Ardelyx scientists. In 2015, the Fremont, CA-based firm regained rights to its NHE3 inhibitor portfolio from AstraZeneca on the termination of the firms' 3-year collaboration to develop the compounds.