Despite drug developers’ best efforts, the path to approval is not always easy. Ask biotechnology company Ardelyx, whose potential treatment option tenapanor was recently rejected by the FDA. According to MedCity News, the drug, designed to treat patients with chronic kidney disease (CKD), cannot be approved without additional clinical data.

Tenapanor

So what exactly is tenapanor? According to Ardelyx, tenapanor is:

a first-in-class, targeted therapy for the treatment of hyperphosphatemia in patients with chronic kidney disease (CKD) on dialysis. Tenapanor…acts locally in the gut to inhibit the sodium/hydrogen exchanger 3 (NHE3) [which] results in a conformational change of the epithelial cell junctions, reducing permeability specific to phosphate, resulting in decreased phosphate absorption through the…primary pathway of dietary phosphate absorption.

Normally, patients with hyperphosphatemia caused by CKD are treated with phosphate binders. However, these can be time-consuming to take, requiring multiple pills taken at every meal. Alternately, tenapanor would offer a singular pill 2x daily, offering increased convenience and efficacy. So far, the treatment has been evaluated in three separate Phase 3 clinical trials, which showed that the drug was well-tolerated and effective in reducing phosphate levels.

FDA Rejection

So what is the cause of the FDA’s rejection? From what we understand, the FDA does confirm that tenapanor shows efficacy in reducing serum phosphorus in patients with CKD. However, the FDA also notes that there is unclear clinical significance. Early this year, the FDA asked for more clinical data regarding how tenapanor differed in efficacy from phosphate binders and the current standard-of-care. Now, to approve the drug, the FDA requested an additional clinical trial to be held. Unfortunately, the FDA also denied a request to discuss the issue of clinical relevance, though Ardelyx does hope to meet with the FDA soon to further understand how to fulfill the necessary requirements for drug approval. Meanwhile, Ardelyx disagrees with the assertion that there is not enough clinical significance regarding treatment efficacy.

Chronic Kidney Disease (CKD)

Also known as chronic kidney failure, chronic kidney disease (CKD) refers to progressively worsening kidney damage, sustained throughout one’s life. Typically, CKD results from another disease or condition, such as diabetes, polycystic kidney disease, pyelonephritis, urinary tract obstructions, or glomerulonephritis (among others). As kidney damage worsens, fluid, wastes, and electrolytes accumulate throughout the body; the kidneys are no longer able to filter them out. Symptoms associated with CKD include:

• Nausea and vomiting
• Jaundice (yellowing of the skin and eyes)
• Appetite loss
• Muscle cramping
• High blood pressure
• Pruritus (intense itching)
• Swelling of the lower extremities
• Changes in urination
• Fatigue and general malaise
• Enlarged spleen and liver
• Shortness of breath