AstraZeneca's drive to extend the life of its blockbuster acid reflux drug Nexium through new uses was set back on Tuesday after U.S. regulators delayed approval of a drug combining it with aspirin.

Nexium, a $5 billion-a-year seller, faces the loss of patent protection in key markets and AstraZeneca is developing novel formulations to extend its franchise.

The Anglo-Swedish drugmaker said it got a Complete Response Letter (CRL) from the U.S. Food and Drug Administration for its application to market Axanum, which combines aspirin with esomeprazole, the active ingredient in Nexium.

It also received a CRL for the supplemental use of Nexium for reducing the risk of low-dose aspirin-associated peptic ulcers.

The U.S. watchdog issues CRLs when it needs more information about an application before approving a medicine. AstraZeneca said would continue discussions with the FDA to determine the next steps and would respond to the request for additional information.

The delay for Axanum follows success with another Nexium line extension product, Vimovo, which won a green light from the FDA at the end of April. Vimovo, developed with Pozen, combines the anti-inflammatory drug naproxen and esomeprazole.

AstraZeneca faces another regulatory hurdle on Wednesday when an FDA expert panel meets to consider whether to approve its new infant lung drug motavizumab.

Winning over the panel may be tough, after FDA staff reported in briefing documents released last week that the drug carried a higher risk of causing severe allergic reactions than the company's older product Synagis.

(Reporting by Ben Hirschler; Editing by Louise Heavens)