Brennan, who has headed AstraZeneca since 2006, announced Thursday, April 26, that he plans to retire and relinquish his board responsibilities on June 1. Simon Lowth, AstraZeneca's executive director and chief financial officer, will serve as interim CEO until a permanent successor is chosen.

"I have decided that now is the right time to step down and allow a new leader to take the reins," Brennan said in a statement.

AstraZeneca also announced that Leif Johansson will replace Louis Schweitzer as nonexecutive chairman on June 1, three months earlier than had been originally planned. Johansson -- a Swedish businessman who was the president and CEO of Volvo AB for 14 years before stepping down in 2010 -- will lead the selection process for Brennan's successor.

Brennan's announcement comes as AstraZeneca finds itself at a crossroads. The company has had several clinical setbacks over the past few years (most recently it scrapped what had been a potential $1.2 billion licensing deal to develop a novel antidepressant with Targacept Inc. after the compound flunked late-stage trials) and its last megadeal, a $15.2 billion buyout of Medimmune Inc. in 2007, didn't produce the expected pipeline results. Making matters worse, it now faces one of the steepest patent cliffs in the sector.

Antipsychotic drug Seroquel, which brought in $5.8 billion of AstraZeneca's $33.59 billion in revenue in 2011, lost patent protection in March. High blood pressure treatment Atacand posted $1.45 billion in sales last year and will hit the patent cliff this year. Top-selling cholesterol drug Crestor -- $6.62 billion in 2011 sales -- as well as gastroesophageal reflux disease pill Nexium, with its nearly $4.5 billion in sales, will also face generic competition in 2014 and 2016, respectively.

AstraZeneca has yet to feel the true impact of Seroquel generics, but generics have already begun pecking away at other key brands such as asthma drug Pulmicort Respules, cancer treatments Casodex and Arimidex, appendicitis and peritonitis injection Merrem, and blood pressure medication Toprol-XL. It cited generic competition for a majority of the 11% revenue drop it reported in the first-quarter results it released Thursday (from $8.29 billion in the first quarter of 2011 to $7.35 billion this year). All told, AstraZeneca's operating profit plummeted 36% between the first quarter of 2011 and that of 2012. The company's stock dropped from a $45.91 per share close on Wednesday to $43.17 per share during early trading Thursday, a fall of more than 6%.

"The anticipated impact from the loss of exclusivity on several brands, together with challenging market conditions, has made for a difficult start to the year in revenue terms," Brennan said.

AstraZeneca has been restructuring for several years to lessen the impact of its revenue loss, cutting thousands of jobs, instituting billions in share buybacks, and deepening its presence in foreign markets such as China. But analysts believe that AstraZeneca must turn to deals -- particularly M&A -- to restock its pipeline and turn itself around, even though executives have indicated publicly that it prefers bolt-on acquisitions over megamergers.

The company has made two moves in April fitting in with that strategy. First, it struck a deal with Amgen Inc. through which the two will develop and commercialize five anti-inflammatory compounds that Amgen discovered. And just days ago, it agreed to pay $1.26 billion for Ardea Biosciences Inc., which has a treatment for gout patients that is currently in Phase 3 development.

AstraZeneca has indicated more deals are on the horizon. There has been speculation that it could be a potential suitor for diabetes drugmaker Amylin Pharmaceuticals Inc., which is reportedly shopping itself.