In a rapid and painful decision, Pfizer killed torcetrapib. The New York giant suspended all development of the compound and what was believed to be the most expensive clinical Phase III trial in history, the “Illuminate” study.

With a budget of $800 million and 15,000 patients recruited, the trial had routine monthly and quarterly reviews of safety data that triggered the company’s decision. The study’s drug safety monitoring board (DSMB) discovered 82 deaths among patients taking a combination of Lipitor and torcetrapib, an agent to raise good cholesterol. Among patients taking only Lipitor, there were just 51 deaths.

“We were very surprised by the information received from the DSMB, the only body with access to the unblinded safety data. We believed that the study was coming along as expected and this new information was totally unexpected and disappointing, given the potential benefits of this drug,” said Philip Barter, chairman of the steering committee overseeing Pfizer’s “Illuminate” study, and director of the Heart Research Institute in Australia. Lipitor’s safety record remains unblemished.

The decision was clearly sudden. According to an FDA statement about Pfizer’s decision, the big company’s DSMB had notified Pfizer of a mortality signal early on Saturday, Dec. 2. By 4:00 p.m. the same afternoon, the FDA said, it had received word from Pfizer that all work on torcetrapib had been halted.

The FDA issued a statement quoting no officials by name. In part, it read: “FDA fully supports Pfizer’s decision to suspend this trial. The system of biomedical research monitoring was effective in this case, assuring that once a certain signal was seen, the trial was halted. FDA will continue to work with Pfizer and other sponsors developing molecules in this class of drugs to ensure that appropriate protections are in place to identify any safety signals as early in the development process as possible.”

In the initial round of news coverage, major newspapers quoted stunned and surprised cardiologists. Most had expected the drug to be a useful and potent addition to their arsenal. As the week unfolds, however, the doubters and critics of the compound are sure to emerge.

Although the trial was scheduled to take a few more years, wrapping up in 2009, Pfizer had expected to file for approval late in 2007.  Just days before its Dec. 2, 2006, decision, Pfizer’s research boss, John LaMattina had said: “We believe this is the most important new development in cardiovascular medicine in years.” Now Pfizer will be obliged to go back to the drawing board, resuscitating once-spurned heart compounds that do not elevate blood pressure.

It was a bad week for the company during a year when its former CEO had been forced out over what Wall Street perceived as excessive compensation and mediocre performance. Pfizer recently announced plans to save $400 million annually by firing a fifth of its sales force, or some 2,000-2,400 representatives. With a quarter of all company revenues at stake in 2010, when the $12 billion Lipitor loses patent protection, the big company’s research pipeline is thin. That’s despite one of the largest research budgets of any company in the world. Additional layoffs seem hard to avoid.

“We understand the challenge that this represents and we will respond quickly and aggressively to it,” new Pfizer CEO Jeffrey Kindler said. “It is important to put this information in the context of both our commitment to transform Pfizer and our overall product and financial strength.”

Kindler’s swift decision on torcetrapib should be heralded as one that serves public health. But prior to his arrival, Pfizer’s choice to tie the two drugs into one combination study will be second-guessed and debated. Unless the company were to revive the drug for another look, it will now be impossible to know whether some subpopulation of patients might have been well served by torcetrapib alone.

After a series of mergers, Pfizer is now so large that lifting its revenues or profits would be difficult under any circumstances. But the present environment is also one in which any drug safety issues are subject to exacting and immediate scrutiny. The scientific and legal record shows that Merck debated its course on Vioxx for years. In this case, Pfizer seems to have decided it did not have that kind of time. The sheer rapidity of its decision (with the company still trying to notify Illuminate investigators) heralds an era in which systems to support lightning-fast decisions will be vital.