The FDA has issued a complete response letter (CRL) regarding the new drug application for ZS-9 (sodium zirconium cyclosilicate, ZS Pharma/AstraZeneca), which is being developed for the treatment of patients with hyperkalemia.
CRLs typically outline concerns and conditions that must be addressed to gain FDA approval. The CRL for ZS-9 followed an inspection by the FDA of the drug’s manufacturing facility. The CRL does not require the generation of any new clinical data.
This is the second time the FDA has declined to approve ZS-9, which AstraZeneca acquired when it bought ZS Pharma in 2015.
ZS-9 is a powder for oral suspension. The active ingredient is a nonabsorbed zirconium silicate that preferentially exchanges potassium for hydrogen and sodium. Clinical trials have indicated that the compound is stable at room temperature and has a rapid onset of action, according to AstraZeneca. The FDA submission included data from double-blind, placebo-controlled trials and an 11-month open-label extension study in adults with hyperkalemia.
Hyperkalemia occurs in 23% to 47% of patients with chronic kidney disease and/or chronic heart failure and may lead to cardiac arrest and death. The mortality rate can be as high as 30% in patients with severe hyperkalemia if the disorder is not treated. Commonly used heart medications can also cause hyperkalemia.