The FDA handed down a major shock to AstraZeneca ($AZN) yesterday when it rejected its key hyperkalemia drug ZS-9, leaving potential rival Relypsa’s ($RLYP) shares to jump in after-hours trading.

Relypsa already markets its hyperkalemia treatment Veltassa, but AstraZeneca was meant to swoop in and take the lion’s share of a market potentially worth $6 billion.

Make no mistake, this is a major blow to AstraZeneca, which just last year paid out $2.7 billion for ZS Pharma ($ZSPH) to gain access to the drug, with Relypsa’s shares typically ticking downward in the past 6 months in expectation of its Big Pharma-backed rival gaining the green light.

Many analysts believed an AstraZeneca approval was a no-brainer, and its candidate has been seen as more favorable by analysts given concerns over Veltassa’s black-box warning issued by the FDA alongside its approval in late 2015.

Last year, after Veltassa’s approval, Credit Suisse analyst Vamil Divan said that his firm “continue[s] to believe that ZS-9 has an overall stronger clinical profile than Veltassa, highlighted by ZS-9’s rapid and consistent efficacy along with more favorable tolerability”--highlighting a fairly typical sentiment among analysts.

In fact, Veltassa came with the strictest black-box warning--which recommends against the administration of the drug with another oral medication at least 6 hours before and after.

But ZS-9 has also come with some safety issues during testing, and some believed it too may face a black-box warning of its own, or even a rejection.

Today, AstraZeneca confirmed that the FDA has issued a Complete Response Letter (CRL) for its ZS-9 NDA--but not over safety fears. “The CRL refers to observations arising from a pre-approval manufacturing inspection,” the Anglo-Swedish drugmaker said in a statement.

For the full article by FierceBiotech, please go here.