The FDA noted the extent of the treatment effect of tenapanor is of unclear clinical significance, despite evidence of efficacy.
The US Food and Drug Administration (FDA) has issued a Complete Response Letter (CRL) regarding the New Drug Application (NDA) for tenapanor for the control of serum phosphorus in adult patients with chronic kidney disease (CKD) on dialysis.
The CRL was issued to Ardelyx, Inc.
The FDA noted in the CRL that while the submitted data provided substantial evidence of efficacy in reducing serum phosphorus in CKD patients on dialysis, the extent of the treatment effect is of unclear clinical significance.
In addition, for the application to be approved, the company will need to conduct an additional trial to demonstrate clinically relevant treatment effects on serum phosphorus or on the clinical outcome assumed to be caused by hyperphosphatemia in the patient population.
No safety, clinical pharmacology, or non-clinical issues were identified within the CRL.
The company is expected to request a Type A meeting with the FDA to discuss the CRL and the potential to move forward in the approval process.
Mike Raab, president and chief executive of Ardelyx, noted the company’s disappointment stemming from the decision by the FDA in a statement.
"We continue to believe tenapanor represents an important, first-in-class treatment option for patients with elevated phosphorus,” Raab said. “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.”
Further, Arnold Silva, MD, PhD, director of Clinical Research at Boise Kidney and Hypertension Institute, added his perspective on the negative consequences of poorly managed serum phosphorus and the need for new therapies.
“I've closely followed the extensive clinical development of tenapanor, not only as an interested nephrologist, but also as a clinical investigator,” Silva said. “I've seen the clinical benefits of tenapanor first-hand in my patients and I'm stunned that the FDA is not granting approval of this novel mechanism drug, despite extensive clinical data demonstrating its safety and efficacy."
Last week, the FDA issued a letter to Ardelyx, Inc. identifying deficiencies in the NDA for tenapanor. They noted key issues included size and clinical relevance of the treatment effect.