New top-line results from a phase III study of Ardelyx Inc.'s tenapanor – recently approved in irritable bowel syndrome – confirmed the drug can also help dialysis-dependent chronic kidney disease patients with hyperphosphatemia achieve reduced serum phosphorus levels vs. placebo. Calling the results "the capstone" to his company's development program, Ardelyx CEO Mike Raab said the medicine "will completely disrupt and displace the binder market as a new treatment option with dosing of just one small pill twice a day."
Company shares (NASDAQ:ARDX) rose 11.2% to $8.05 on Tuesday. A mid-2020 NDA filing is planned, with a potential approval to come in mid-2021.
Tenapanor won FDA approval for use in irritable bowel syndrome with constipation in September, for which it is marketed as Ibsrela.
The pivotal one-year phosphate-lowering study, called Phreedom, met its primary endpoint demonstrating a statistically significant difference in least square mean serum phosphorus change (-1.4 mg/dL, p<0.0001) for tenapanor vs. placebo. During the 26-week treatment period, 77% of tenapanor-treated patients in the intent-to-treat population (n=408) had a decrease in serum phosphorus, with a mean reduction from baseline of 2 mg/dL.
Analysts welcomed the new data as helping to move the drug one step closer to a potential approval in hyperphosphatemia, noting that the phosphate-lowering effects seen in Phreedom compared favorably with those seen in Ardelyx's previously released phase III Amplify trial results, which demonstrated the benefits of a dual mechanism approach with tenapanor plus binders in those who require more aggressive phosphate management. Patients treated in the tenapanor arm of that study, in combination with phosphate binders, had a statistically significant mean reduction in serum phosphorus from baseline to the end of the four-week treatment period vs. those treated in the binder-only arm (0.84 vs. 0.19, p=0.0004).
Tenapanor, a sodium hydrogen exchanger 2 inhibitor, is designed to reduce the absorption of dietary sodium in the bloodstream. That results in more sodium in the gut, which boosts fluid and loosens stool. As anticipated by the company due to the mechanism of action, during Phreedom the most common self-reported adverse event was loose stools/diarrhea at an incidence rate of 52.5%, with about 90% of the events judged by the investigator to be mild to moderate in nature. Investigators in the study saw a 16% discontinuation rate among patients on tenapanor due to diarrhea. Though that might have muted market reaction to the results, Piper Jaffray analyst Christopher Raymond said that "we continue to view the previously disclosed safety data from [the Amplify study] as better representative of real-world results, which saw a discontinuation rate of just 2.6%."
If approved in hyperphosphatemia, tenapanor as a monotherapy faces competition from phosphate binders such Renagel (sevelamer, Sanofi SA), which are prescribed to more than 95% of patients undergoing dialysis to assist in the management of the condition. However, during a conference call held Tuesday to discuss the data, Raab seemed to suggest the drug could prove a particularly attractive option in the treatment of patients "on the far end of the spectrum that we demonstrated with Amplify, those very difficult-to-treat patients who have extremely high serum phosphorus levels, who are prescribed and on very large doses of binders, yet are still well above the 5.5 target that's the customary target for physicians."
In addition to the new Phreedom data, Ardelyx announced initial results from the company's phase IV open-label 18-month extension study, called Normalize. That trial is seeking real-world evidence on synergy between tenapanor and sevelamer for reducing patients' serum phosphorus levels to normal (<4.6 mg/dL) while minimizing their medication burden.
In the initial analysis of 73 patients treated for more than one month so far, 42% had achieved normal serum phosphorus levels and, of those, 58% reached that point with either tenapanor alone or with tenapanor in combination with only one to three sevelamer tablets per day.