AstraZeneca P.L.C. chief executive officer David Brennan said Thursday he would retire June 1 after another difficult quarter for the pharmaceutical manufacturer.

Based in the United Kingdom, AstraZeneca has its U.S. headquarters in Wilmington and a plant in Newark, Del.

The company has struggled lately as it tried to replace revenue, some of which has been lost as blockbuster drugs face generic competition because their patents are expiring.

AstraZeneca's best-selling drugs are Crestor (cardiovascular), Seroquel (antipsychotic), and Nexium (gastrointestinal). The patents for some versions of Seroquel have already expired. Crestor's patent expires in 2016, but even in branded form, it has to compete against other drugs that lower cholesterol.

AstraZeneca has tried adding smaller companies that have potentially profitable drugs in the late stages of development. The latest was this week's $1.26 billion purchase of San Diego-based Ardea Biosciences Inc., which has a promising but not-yet-ready medicine for gout.

Still, the company has had several rounds of layoffs, including among staff in Delaware.

In the first quarter, total revenue fell 11 percent and the net profit dropped 44 percent. Shares on the New York Stock Exchange shed $2.55, or 5.6 percent, to close at $43.36.

"The pharmaceutical sector is experiencing pressures, none of which I've witnessed in my 36 years in the industry," Brennan, 58, said during a Thursday conference call. He has been Astra's CEO since 2006. "I remain very confident that AstraZeneca has the capabilities, courage, and determination to be successful into the future. If we maintain our focus on meeting the needs of patients and trying to solve unmet patient needs, we can continue to deliver attractive and sustained returns for our shareholders."

Board member Leif Johansson will guide the selection for Brennan's successor. Chief financial officer Simon Lowth will act as interim CEO after Brennan departs and until his replacement is named.

Bernstein Research analyst Tim Anderson said the company had been shareholder-friendly with stock buybacks and dividends, but the five-year financial outlook was "uninspiring."

Anderson wrote to clients, "Coupled with what appears to be a thinner late-stage pipeline and a mixed longer-term R&D track record, the multiyear view of AZN is challenging in our view."

Contact David Sell at 215-854-4506 or dsell@phillynews.com or Twitter @PhillyPharma. Read his "PhillyPharma" blog on philly.com.