Ardelyx's kidney disease drug hits goal in phase 3, teeing it up for FDA filing

A phase 3 trial of Ardelyx’s tenapanor in chronic kidney disease (CKD) patients on dialysis has met its primary endpoint. The success comes months after tenapanor hit the mark in another pivotal clinical trial, putting Ardelyx on track to file for approval in the indication around the middle of next year. 

In September, Ardelyx reported two pieces of positive news in quick succession, first sharing data from a phase 3 trial of tenapanor in CKD patients on dialysis and then winning FDA approval for the drug in irritable bowel syndrome with constipation. Now, Ardelyx has presented top-line data from a second phase 3 trial that could enable it to win approval in a new indication.

The latest phase 3 trial tested the NHE3 sodium transport inhibitor as a monotherapy treatment for elevated blood phosphate levels in CKD patients on dialysis. At the end of the 26-week treatment period, Ardelyx saw a statistically significant difference in the change in phosphate levels across the tenapanor and placebo arms.

That difference, which resulted in a p-value of 0.0001, caused the study to meet its primary endpoint. Ardelyx is yet to share the data behind the result but did report that 77% of patients on tenapanor experienced a mean 2.0 mg/dL drop in serum phosphorus from baseline.

As expected, loose stools and diarrhea feature prominently in the safety and tolerability data. More than half of people on tenapanor suffered these side effects. As in the previous CKD phase 3, most of the events happened early in the trial and were transient. However, this time around the symptoms were bad enough to make 16% of tenapanor patients discontinue, compared to 3% in the prior trial. The earlier trial tested tenapanor in combination with phosphate binders.

Ardelyx thinks the benefits outweigh the risks considering the links between elevated phosphorous levels and the 18% mortality rate in dialysis patients. Some analysts have reached similar conclusions, with Piper Jaffray’s Christopher Raymond tipping tenapanor to rack up blockbuster sales.

Work to gain the regulatory authorizations needed to live up to those expectations is underway. With tenapanor succeeding as a monotherapy and in combination in phase 3, Ardelyx plans to file for FDA approval around the middle of next year.

Shares in Ardelyx rose as much as 10% in premarket trading, adding to the more than 300% increase in the price of the stock since the start of the year. The increase and events behind it have validated Ardelyx’s decision to pay $25 million to buy back the rights to tenapanor from AstraZeneca.