The FDA has hit Ardelyx’s chronic kidney disease (CKD) drug candidate tenapanor with a complete response letter. Ardelyx disclosed the setback 10 days after revealing the FDA had identified concerns with the treatment effect and its clinical relevance.
Tenapanor is designed to treat an electrolyte disorder that affects patients on dialysis by inhibiting the sodium-proton exchanger NHE3. Ardelyx went to the FDA armed with data from three phase 3 clinical trials that, in its view, showed tenapanor cuts phosphate levels when given as a single agent and with phosphate binders.
The FDA agreed that “the submitted data provide substantial evidence that tenapanor is effective in reducing serum phosphorus in CKD patients on dialysis,” according to Ardelyx, but said the treatment effect is “small and of unclear clinical significance.”
Ardelyx will need to address that perception to get tenapanor approved. The FDA has asked Ardelyx to run “an additional adequate and well-controlled trial demonstrating a clinically relevant treatment effect on serum phosphorus or an effect on the clinical outcome thought to be caused by hyperphosphatemia in CKD patients on dialysis.”
In a statement to disclose the setback, Ardelyx CEO Mike Raab said he disagrees with “the FDA’s subjective assessment on the clinical relevance of the treatment effect of tenapanor” and will work with the agency to find “an expeditious path forward.” Ardelyx will know more after meeting with the FDA but the path to market for tenapanor may be long.
“It is unlikely that [Ardelyx] will have a short path to approval because tenapanor’s efficacy appears to be in question,” analysts at Jefferies wrote in a note to investors. “We expect a higher bar required in terms of PO4+ lowering or a head-to-head comparison w/ binders. While this certainly provides [the company] a path forward, we do not see much room for a short approval timeline.”
Despite that assessment, the analysts described the outcome as “decent” given the circumstances. The circumstances facing Ardelyx began to become clear earlier in July, when it revealed that the FDA had “identified deficiencies that preclude discussion of labeling and post-marketing requirements.” The earlier notice sank Ardelyx’s stock.
Ardelyx ended June with $172 million in cash and equivalents. A second candidate, RDX-013, is in phase 2 development as a treatment for high serum potassium levels in patients with CKD.