The FDA has issued a complete response letter (CRL) regarding the new drug application for ZS-9 (sodium zirconium cyclosilicate, ZS Pharma/AstraZeneca), an investigational medication being developed for the treatment of patients with hyperkalemia. The CRL refers to observations arising from a pre-approval manufacturing inspection. The FDA also acknowledged the receipt of recently submitted manufacturing data, which it has yet to review. The CRL does not require the generation of new clinical data.
ZS-9 is an insoluble, nonabsorbed compound with a structure that was designed to preferentially trap potassium ions. In in vitro studies, the potassium selectivity of ZS-9 resulted in a high binding capacity for potassium ions in the presence of other competing ions. ZS-9 has been studied in three double-blind, placebo-controlled trials and in one ongoing 12-month open-label trial in patients with hyperkalemia, representing more than 1,600 treated patients. ZS-9 is an investigational product that is not currently approved for any indication in any market.
The FDA’s decision came as a big surprise to AstraZeneca, according to a report from FierceBiotech. Last year, the company paid $2.7 billion for ZS Pharma to gain access to ZS-9. The drug was being positioned to grab some of the hyperkalemia market away from Relypsa Inc.’s Veltassa (patiromer).
Hyperkalemia (potassium levels of greater than 5.0 mEq/L in the blood serum) occurs in 23% to 47% of patients with advanced chronic kidney disease and/or chronic heart failure, and may lead to cardiac arrest and death. Up to 30% of patients with severe hyperkalemia may die if the disorder isn’t treated rapidly. Treatment with common heart medications (renin–angiotensin–aldosterone system [RAAS] inhibitors) can also be responsible for hyperkalemia. Current therapeutic options are limited, resulting in a significant unmet medical need.