By Jonathan D. Rockoff 

Bristol-Myers Squibb Co. said Tuesday that Chief Operating Officer Giovanni Caforio will become its next chief executive, as the leaders who turned the pharmaceutical company into an immunotherapy powerhouse exit.

Dr. Caforio, 50, will succeed 64-year-old Lamberto Andreotti, effective May 5. Mr. Andreotti has been Bristol's CEO since 2010 and will become executive chairman of the company's board of directors after retiring Aug. 3.

A trained physician, Dr. Caforio joined Bristol in 2000 as general manager of its Italy business and has since been rising through the company's ranks. In recent years, he has been leading the commercialization of Bristol's two newly approved cancer drugs, which work by unleashing the body's immune system to fight cancer.

Such immunotherapies are a new class of medicines, which industry officials consider to be transforming cancer treatment. J.P. Morgan estimates the drugs could command $25 billion in yearly sales eventually.

Part of Dr. Caforio's charge as CEO will be to maintain Bristol's early lead in the market despite heavy and increasing competition from rivals including Merck & Co., which already is selling one of the drugs.

"I look forward to working with our very talented team of people at BMS to build on what we've accomplished, to deliver on the promise of our innovative portfolio and to continue to make a real difference for our patients," he said in a statement.

Bristol pioneered the move into immunotherapies, starting with its $2.4 billion purchase of Medarex and then winning approval, in 2013, of skin-cancer immunotherapy Yervoy. Late last year, Bristol received approval for a second immunotherapy, Opdivo, also for skin cancer.

Now the company is exploring use of its immunotherapy drugs to treat other cancers and in combination with other kinds of therapies.

The focus on immunotherapy was part of Bristol's pivot from a traditional, diversified big drug maker into one focused on treating more specialized conditions, like cancer.

Bristol used deals like the acquisition of Medarex to reshape its portfolio, while shedding noncore businesses selling infant formula and other products. The company was trying to prepare for the patent expirations of top-selling products like Plavix and antihypertensive Avapro.

The transformation hasn't been seamless. Bristol's efforts to gain a foothold in hepatitis C treatment were set back after its $2.5 billion deal for Inhibitex in 2012 foundered because a promising drug program had to be terminated for safety reasons.

Bristol shares rose 11.06% in 2014, compared with a 19.1% gain for the S&P 500 Pharmaceuticals Index, according to FactSet.

Mr. Andreotti was among the Bristol executives who conceived and executed the makeover. Also spearheading the changes was James Cornelius, currently Bristol's nonexecutive chairman, who became the company's CEO after the previous leader was forced out in a scandal involving efforts to delay a generic version of Plavix.

Mr. Cornelius, 71, will retire from the board as part of the leadership changes, Bristol said. Other architects of Bristol's transformation have previously left the company, including executives Elliott Sigal and Jeremy Levin.

Write to Jonathan D. Rockoff at Jonathan.Rockoff@wsj.com

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