The regulator says it can resubmit the application once deficiencies are tackled
The FDA has dealt another blow to AstraZeneca by declining to approve ZS-9, a drug for high potassium levels in the blood, which was the main asset in AZ's $2.7bn acquisition of ZS Pharma in 2015.
The US regulator issued a Complete Response Letter to ZS Pharma regarding its application for ZS-9 (sodium zirconium cyclosilicate) as a treatment for the condition - known as hyperkalaemia - after an inspection of the manufacturing plant for the drug. It follows an earlier rejection of the drug in 2015, which once again resulted from a manufacturing inspection.
ZS Pharma - which now operates as a subsidiary of AZ - is not saying much about the nature of the deficiencies uncovered at the plant, although it stressed that the FDA has not asked for any new clinical data. The second rejection is something of an embarrassment for the company however, and could hold back approval by another year if AZ has to refile.
Under FDA regulations AZ can now resubmit the application once the deficiencies are tackled, withdraw the application or request an open hearing to discuss the grounds for the FDA's refusal to approve.
In Europe, ZS-9 has already been granted a positive opinion by the Committee for Medicinal Products for Human Use (CHMP), and AZ said it is now looking into the possible implications of the FDA's action on other regulatory filings.
"AZ and ZS Pharma are committed to working with the FDA to resolve the remaining matters under review as soon as possible," it said in a statement.
When AZ bought ZS Pharma it described ZS-9 as a "best in class" potassium-binder with sales potential in excess of $1bn a year. Elevated serum potassium is associated with multiple diseases - including chronic heart failure (CHF) and chronic kidney disease (CKD) - and can lead to potentially fatal abnormal heart rhythms.
On the plus side for AZ it seems that safety is not causing a concern for the regulator - something that resulted in rival drug Veltassa (patiromer) from Relypsa - now part of Galenica's Vifor Pharma unit - needing a black box warning on its US labelling. The warning - that required its dosing to be separated from other oral medicines - was removed last year after additional data was submitted to the FDA.
Veltassa was launched in early 2016 - becoming the first new drug for hyperkalaemia in decades - but take-up has been slow with sales of around $12m last year. Vifor filed for approval of the drug in Europe last April, and now has a larger window of opportunity to grow its drug before AZ can compete head-to-head in the market.