- Ardelyx disclosed late Monday the Food and Drug Administration found "deficiencies" with the company's application to approve its lead drug for patients with kidney disease, a surprise announcement that sent shares falling more than 70%.
- Ardelyx developed its drug, called tenapanor, as a way for people with chronic kidney disease to control their phosphorus levels. The biotech reported success in multiple Phase 3 trials, but said the FDA took issue with the "size of the treatment effect" observed in testing and "its clinical relevance," putting the treatment's future in doubt for that indication.
- While not definitive, the FDA's feedback was delivered less than two weeks before the agency's deadline to decide on tenapanor's use in kidney disease patients. A rejection is now likely before the end of the month, wrote Piper Sandler analyst Christopher Raymond.
Over the past year, the FDA has alternatively been seen as too lenient or too harsh, depending on the circumstances. The controversial approval of Biogen's Alzheimer's drug Aduhelm, for instance, sparked outrage from critics who believe the regulator substantially lowered its standards. But the agency has been tougher elsewhere, delaying a number of gene and cell therapy programs over manufacturing concerns and, more recently, calling out several biotechs for "deficiencies" in approval applications.
Those decisions, taken together, have created a regulatory environment Piper Sandler's Raymond described as "much less predictable or reliable." Ardelyx's case is the latest example.
The biotech has survived a number of setbacks since its founding in 2007 — including two lost partnerships with AstraZeneca and Sanofi — but finally broke through with a double dose of good news in September 2019. That month, the agency approved tenapanor to treat irritable bowel syndrome. And Ardelyx also found the drug, when combined with other treatments, helped lower the dangerous buildup of phosphate in the blood of people with chronic kidney disease in a Phase 3 trial.
Ardelyx succeeded with two other late-stage studies testing tenapanor as a monotherapy and appeared on track for an approval in April. But the FDA delayed its decision by three months, asking Ardelyx for an additional analysis "to help the agency better understand" the data in light of the drug's "novel mechanism of action."
Discussions about the drug's potential label continued, but recently came to a halt. Ardelyx said it received a letter on July 13 outlining deficiencies in its application. The FDA didn't provide specifics, according to the company, only noting a "key issue" was the size and relevance of the treatment effect. The biotech was denied a request for a meeting to discuss those deficiencies.
"This is an extremely disheartening and disappointing communication from the FDA, particularly following the weeks of label discussions that occurred in early April, the fact that our NDA submission included three pivotal trials across 1,000 patients, all which met their primary and key secondary endpoints, as well as the additional data analyses we submitted in late April in response to the FDA's requests," said Ardelyx CEO Mike Raab in a statement.
Raab said the company aimed to work with the FDA to learn more about the problems and fix them, but the damage appears done. The news surprised Piper Sandler's Raymond, who noted the agency helped Ardelyx design the trial and that the letter may indicate the FDA is taking issue with using phosphate levels as a study goal.
"We find this move almost as mind-boggling as the Aduhelm decision, and believe decisions like these — troublingly — are beginning to erode what heretofore has been a stellar example of regulatory excellence," Raymond wrote.
Ardelyx's setbacks follows similar outcomes for Acadia Pharmaceuticals, Provention Bio and Vanda Pharmaceuticals, each of which received FDA letters about drug application "deficiencies" over the past few years. The FDA rejected each of their approval requests.
A decision on tenapanor is due by July 29.