Some AstraZeneca investors are reportedly calling for a change at the top of the company and are questioning the leadership of chief executive David Brennan.

The Financial Times has published an article based on comments made by undisclosed large shareholders who want “a radical shake-up of the board and executive team”. The FT notes that some of AstraZeneca’s top 20 investors have become "unusually and increasingly vocal in recent weeks", with one telling the newspaper that “the CEO is under intense pressure".

One shareholder said there has been some lobbying to replace Mr Brennan with chief financial officer Simon Lowth, although another claimed that the latter "lacked the breadth to take over". The source claims Mr Brennan was likely to step down by the time of his 60th birthday next year, "but the board will probably step in and take a new strategic direction because the company is in a downward spiral".

These are pretty tough times at the Anglo-Swedish drugmaker and the acquisitions of Cambridge Antibody Technology for $1.3 billion in 2006 and MedImmune in 2007 for $15.6 billion, both under Mr Brennan's watch, have not proved successful buys. Several late-stage failures have also led to criticism of the way AstraZeneca has conducted its research.

However, as the FT notes, many observers believe Mr Brennan, who took over as CEO from Sir Tom McKillop at the start of 2006, has done a pretty good job. Under his leadership, AstraZeneca is a major player in the emerging markets, notably establishing itself as a market leader in China, while the cholesterol-lowerer Crestor (rosuvastatin) has emerged as an enormous seller. Also the firm has been fighting hard to protect its antipsychotic franchise Seroquel (quetiapine fumarate) franchise from generic threats.

Mr Brennan has also led a major restructuring and Gbola Amusa, an analyst at UBS, told the FT that efficiency gains have helped generate strong total shareholder returns, with healthy dividends being paid out. However he also believes that major M&A activity may be necessary to cure AstraZeneca's ills, arguing that "if you cut $2 billion a year in research for infinity, and used it to finance acquisitions, it would be highly rewarded".

AstraZeneca is regularly mentioned as a buyer when potential deals are thrown into the mix but Mr Brennan has repeatedly ruled out transformational purchases.