Tenapanor, a therapeutic for end-stage renal disease patients who are on dialysis and have too much phosphate in their blood, was well-tolerated and met the goals of a Phase 3 clinical trial to determine its effectiveness and safety, according to Ardelyx, the drug’s developer.
Tenapanor (also known as AZD1722 and RDX5791) is a small molecule that has consistently demonstrated the ability to reduce the absorption of dietary sodium and phosphorus, both of which are key factors in the progression of kidney disease.
The drug is being tested to control hyperphosphatemia, which is an abnormally elevated levels of phosphate in the blood, in patients with end-stage renal disease (ESRD) and with chronic kidney disease (CDK) who are on dialysis. It also may be useful to treat irritable bowel syndrome and constipation (IBS-C).
The eight-week, multi-center, randomized, double-blind clinical trial (NCT02675998) with a four-week, placebo-controlled, randomized withdrawal period, evaluated the effectiveness, safety, and tolerability of tenapanor to treat hyperphosphatemia in 219 ESRD patients on hemodialysis. Patients were randomized to either 3 mg, 10 mg , or a titration regimen (optimization of dose) of tenapanor.
Ardelyx reported that at the end of the eight-week treatment, 80 patients, out of 164, had an average reduction in serum phosphorus levels from baseline of 2.56 mg/dL, with a reduction of up to 5.7 mg/dL. Thirty-three percent of patients had reduction in serum phosphorus superior to 3 mg/dL.
The trial met its primary endpoint. From the end of the eight-week treatment period to the end of the four-week randomized withdrawal period further, there were statistically significant differences between tenapanor-treated patients and placebo, regarding serum phosphorus levels.
“The reduction in serum phosphorus in many patients treated with tenapanor is remarkable. These data validate tenapanor’s unique mechanism of action and its potential to be the first non-phosphate binder treatment for this difficult-to-manage disorder,” Geoff Block MD, director of clinical research at Colorado Kidney Care, and a Phase 3 investigator, said in a press release. “My patients are often required to take more than 19 pills per day, of which, nearly half are phosphate binders. The efficacy of tenapanor with only a few small pills, combined with its GI tolerability, has the potential to change the way in which we treat our patients in the future. I look forward to participating in the next Phase 3 study and evaluating the full potential of this novel agent.”
In the trial, tenapanor was well-tolerated, with the only treatment-related adverse event being diarrhea (affecting 39% of patients), which led to treatment-discontinuation in 17 patients. Loosened stool or increased frequency in bowel movements, regardless of magnitude, was observed in one patient.
“We are very pleased with the overall efficacy and improved tolerability profile of tenapanor in this study. The magnitude of the reduction of serum phosphorus in a large percentage of patients treated with tenapanor in this trial surpassed our expectations,” said Mike Raab, president and CEO of Ardelyx. “We are highly confident in tenapanor and look forward to further establishing its clinical and commercial value in the next Phase 3 trial.”
Ardelyx is planning to begin a second Phase 3 clinical trial evaluating tenapanor in the same clinical population by mid-year.
Detailed results from the first Phase 3 study will be presented at American Society of Nephrology Kidney Week in New Orleans, Oct. 31- Nov. 5, 2017.