- A medicine meant to help kidney disease patients has been rejected by the Food and Drug Administration, as the agency wants to see more evidence that it affects clinical outcomes.
- Ardelyx, a bi-costal biotech developing treatments for the heart and kidneys, announced the rejection Thursday. In clinical trials, its medicine, called tenapanor, significantly lowered phosphorous levels in patients with chronic kidney disease, a condition that makes it difficult to filter excess amounts of the compound from the blood.
- Despite those results, the FDA recently flagged "deficiencies" in the drug's approval application. Specifically, regulators questioned how impactful tenapanor was during testing, and whether it demonstrated "clinical relevance." Those same concerns were at the center of the newly issued rejection letter, Ardelyx said Thursday. To address them, the company must run another "adequate and well-controlled trial demonstrating a clinically relevant treatment effect," a task analysts think would take some time to accomplish.
The FDA's decision wasn't surprising to analysts, as "deficiencies" in an approval application have become somewhat of a prelude to rejection. This year alone saw two other drugmakers, Provention Bio and Acadia Pharmaceuticals, receive negative feedback about their applications shortly before the FDA turned them down.
For Ardelyx, the path forward revolves around a new clinical trial. The company said it intends to request a meeting with the FDA "as soon as possible" to go over the rejection and what would be needed to gain approval.
The request for another trial provides a "sliver of hope," according to Jefferies analyst Chris Howerton. And yet, the rejection still substantially delays the program.
"We think this is a decent outcome ... given the circumstance," Howerton wrote in a note to clients, "but it is unlikely that [Ardelyx] will have a short path to approval because tenapanor's efficacy appears to be in question."
Given these new uncertainties, Cantor Fitzgerald analyst Louise Chen lowered her estimate for the odds that tenapanor gets approved from 90% to 70%. Chen also predicted that, with another trial needed, a tenapanor launch in chronic kidney disease likely can't happen until 2024.
Ardelyx shares were down about 1% late Friday morning, trading at $1.69 apiece. The company's share price has fallen roughly 80% since July 19, when it announced the FDA had taken issue with its approval application.
"We do not agree with the FDA's subjective assessment on the clinical relevance of the treatment effect of tenapanor in our studies which met all clinical endpoints agreed upon by the FDA," said Mike Raab, Ardelyx's CEO, in a statement. "In our view, the serum phosphorus lowering data generated with tenapanor in all of our clinical studies is meaningful and clinically significant."
Tenapanor is already on the market, having secured approval in 2019 for the treatment of irritable bowel syndrome with constipation in 2019. However, Ardelyx has noted in financial reports that the company has not generated any revenue from commercial product sales. It ended 2020 with a net loss of $94 million, and as of June 30, it had $172 million in cash and cash equivalents.
Chronic kidney disease therefore represents a valuable indication for Ardelyx. The Centers for Disease Control and Prevention estimates that 15% of adults in the United States — equivalent to 37 million people — are living with the illness, though most are undiagnosed.
And for many patients, available treatments don't always work sufficiently, which can open the door to major health issues. Too much phosphorous in the blood, for example, can lead to weakened muscles and a buildup of calcium deposits, which may then put patients at increased risk of cardiovascular complications like heart attack, stroke or death.
"Despite our best efforts with currently available therapies, managing phosphorus remains a significant challenge. We need new tools," said Arnold Silva, director of Clinical Research at Boise Kidney and Hypertension Institute, in the statement from Ardelyx.
"I've closely followed the extensive clinical development of tenapanor, not only as an interested nephrologist, but also as a clinical investigator," Silva added. "I've seen the clinical benefits of tenapanor first-hand in my patients and I'm stunned that the FDA is not granting approval."