Billionaire investor Carl Icahn, who last year forced board changes at biotechnology company Biogen Idec Inc , may take aim at cross-town rival Genzyme Corp , according to a source familiar with the situation.

Icahn bought 1.5 million Genzyme shares in the third quarter, and some observers expect him to increase that stake as he considers a proxy assault on the biotech powerhouse.

On Thursday, however, Genzyme launched a pre-emptive strike against Icahn by announcing it had entered into a collaborative agreement with another activist investor, Ralph Whitworth.

The agreement gives Whitworth, who runs Relational Investors LLC and is one of Genzyme's top shareholders, the right to join Genzyme's board. In return, Whitworth has pledged to publicly support and recommend each of Genzyme's board nominees at the company's shareholder meetings.

They are a very constructive firm, Genzyme Chief Executive Henri Termeer said in an interview, in reference to Relational. They have a philosophy of helping in a constructive way, not a destructive way.

Icahn was not immediately available for a comment.

Genzyme, which built itself into one of the world's biggest biotech companies by selling drugs for rare diseases, is struggling to emerge from its worst year ever after a manufacturing crisis led to shortages of two of its life-saving drugs.

The company's shares are trading at their lowest level in five years and investor dissatisfaction is such that Icahn, if he decides to launch an attack, could find some support.

I think shareholders would be willing to listen if there was talk of a change of management, said Derek Taner, who runs the $1 billion AIM Global Health Care Fund and owns an undisclosed number of Genzyme shares. There have been a lot of management missteps that candidly shouldn't have been made.

Last year, Icahn succeeded in placing two directors on the board of Biogen. Some see a similar scenario at Genzyme.

I wouldn't be surprised to see a proxy fight at Genzyme, said Bill Tanner, an analyst at Lazard Capital Markets. People are pretty upset.

Icahn's battle with Biogen took two years. But in December the company replaced its chairman, and on Monday, CEO James Mullen announced he would retire.

Tough though the Biogen fight was, a run at Genzyme, whose headquarters are barely a mile from Biogen's in Cambridge, Massachusetts, could be tougher.

For one thing, Genzyme is a more diverse company with many moving parts.

And unlike Mullen, who ran Biogen but was not defined by it, Termeer, who has been CEO of Genzyme for nearly 25 years, stands at the helm of the company like the captain of an ocean liner. He is likely to fight harder than Mullen, and he has a tightly knit board.

Henri, as much as anyone, has created Genzyme, said Phil Nadeau, an analyst at Cowen & Co. Shareholders and board members are likely to keep that in mind should a proxy fight occur.

On the other hand, Genzyme's missteps are more glaring than they were at Biogen, giving Icahn more concrete material to work with when trying to prove management failure.

Not only was the company forced to close its Allston Landing plant in Boston because of a viral contamination, but vials of its drugs were found to contain metal fragments and non-latex rubber -- debris shed by antiquated equipment.

Most compellingly, the company's shares have clearly underperformed the market. Last year, Genzyme's shares fell 26 percent, while the NYSE Arca Biotech Index rose 46 percent.

In my opinion, and the opinion of Wall Street, Henri has failed to execute well over the past few years, said one portfolio manager who holds about 500,000 Genzyme shares but is only authorized to talk about his top 10 holdings, of which Genzyme is not one. I think there are certain investors who would welcome a management shake-up.

Termeer concedes that the company is vulnerable to investor activism, and says he has been watching the situation next door at Biogen. But he says Genzyme has a much broader pipeline of new drugs than Biogen, which he says is in play.

Carl icahn Investment