The FDA has issued a complete response letter (CRL) to Ardelyx stating that an additional clinical trial is needed to support approval of tenapanor, the company’s novel treatment for the control of serum phosphorus in adult patients with chronic kidney disease (CKD) on dialysis.1
Ardelyx previously submitted a new drug application (NDA) to the FDA hoping to obtain approval of tenapanor in this setting; however, the CRL explained that the data in the NDA left the FDA “unclear of the clinical significance”of the treatment. According to Ardelyx, the CRL did not identify any issues in other key areas, such as safety; clinical pharmacology/biopharmaceutics; chemistry, manufacturing and control; or nonclinical items.
"Lowering serum phosphorus is a priority for me in managing my patients on dialysis, and is an established standard of care driven by the peer-reviewed globally accepted KDIGO clinical practice guidelines. Years of research have demonstrated the negative consequences associated with even slight elevations in serum phosphorus. Despite our best efforts with currently available therapies, managing phosphorus remains a significant challenge. We need new tools,” Arnold Silva, MD, PhD, director of Clinical Research at Boise Kidney and Hypertension Institute, stated in the press release.
“I've closely followed the extensive clinical development of tenapanor, not only as an interested nephrologist, but also as a clinical investigator. 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," added Silva.
Also commenting in the press release, Glenn Chertow, MD, division chief of nephrology and professor of medicine at Stanford University, stated, "Neither peritoneal nor hemodialysis provides adequate control of serum phosphorus, obligating the use of medications. Unfortunately, phosphate binders—individually or in combination—rarely yield consistent control of serum phosphorus concentrations, and persistent hyperphosphatemia leads to dystrophic calcification, accelerated arteriosclerotic vascular disease, fractures, and other complications that profoundly affect patients' lives. The effect of tenapanor on serum phosphorus observed in the phase 3 trials is clinically meaningful. Tenapanor would enable a substantially larger fraction of patients to reach target serum phosphorus concentrations and would yield significant clinical benefit to this vulnerable population."
Regarding next steps with tenapanor Mike Raab, president and chief executive officer of Ardelyx, stated, "We continue to believe tenapanor represents an important, first-in-class treatment option for patients with elevated phosphorus. 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. In our view, the serum phosphorus lowering data generated with tenapanor in all of our clinical studies is meaningful and clinically significant. We will work with the agency to address the issues raised and, to the extent possible, find an expeditious path forward."
1. Ardelyx Receives Complete Response Letter from U.S. FDA for New Drug Application for Tenapanor for the Control of Serum Phosphorus in Adult Patients with CKD on Dialysis. Published online July 29, 2021. Accessed July 30, 2021. https://prn.to/3zNth6c.