Pfizer said yesterday that clinical trials of torcetrapib - a heart medication that is the most important drug in the company's pipeline - confirmed that it raises blood pressure, a potentially serious side effect.
Any problems with torcetrapib would be a serious setback for Pfizer, the world's largest drug company. Pfizer has been counting on the new medicine to eventually replace the $13 billion in annual sales from the cholesterol-lowering drug Lipitor, which loses patent protection in 2010.
Cardiologists and Wall Street analysts alike have been closely watching the clinical trials of torcetrapib, a medicine intended to raise so-called good cholesterol.
Pfizer's stock dropped 2 percent after the announcement by the company, which has been researching torcetrapib for a decade and is spending $800 million to develop it.
Pfizer said it still expected to submit the medicine for federal approval sometime in the second half of next year, with an approval possible in 2008. Pfizer hopes to win approval by showing that a combination of torcetrapib and Lipitor can reduce the formation of plaque in the arteries.
But doctors said that the blood pressure rise was medically significant and would discourage the Food and Drug Administration from approving torcetrapib, even if Pfizer proves next year that the drug does reduce plaque. Instead, Pfizer will now probably have to show that torcetrapib actually lowers the risk of heart attacks and strokes in patients who take it, not just that it cuts plaque, the doctors said.
Pfizer is conducting a 25,000-patient trial to examine whether torcetrapib reduces deaths and heart attacks. But full data from that trial will probably not be available until 2009. The findings described yesterday were preliminary results from more than 4,000 patients already enrolled in that trial.
Among those patients, Pfizer said, torcetrapib caused an average rise of three to four millimeters in their systolic blood pressure, the top number of the blood pressure reading. In other words, a person who had a blood pressure reading of 125 over 80 before entering the trial would generally have a reading of 128 over 80 or 129 over 80 after taking the drug. The difference may seem small, but cardiologists said it was troubling.
"It is a concern," said Dr. Antonio M. Gotto Jr., a cardiologist and the dean of Weill Cornell Medical College in New York. "It doesn't mean the death knell for the drug, but it would probably mean that one would want to see evidence on clinical events before approving the drug."
Earlier clinical trials had also shown that torcetrapib raised blood pressure, but analysts and some doctors had hoped that the effect would decrease in the larger trials. Instead, patients in the new trials actually had an even larger gain in pressure.
If regulators approve the drug, Pfizer expects to sell it alone as well as in combination with Lipitor, which reduces so-called bad cholesterol by 40 percent to 60 percent.
Lipitor and similar medicines, called statins, are the single largest-selling drug category worldwide and among the pharmaceutical industry's biggest breakthroughs in the last generation. Statins are widely credited with helping to lower death rates from heart attacks and strokes.
Pfizer hopes that torcetrapib will prove another breakthrough. The company believes that torcetrapib, in combination with Lipitor, may actually reverse the buildup of the fatty plaques that can block blood vessels and cause heart attacks and strokes.
Dr. Joe Feczko, Pfizer's chief medical officer, said that Pfizer still believed that the benefits of torcetrapib outweighed its risks and that the F.D.A. might still approve the drug based only on its effect on plaques. Data from clinical trials shows that the torcetrapib-Lipitor combination raises good cholesterol 55 percent more than Lipitor alone and reduces bad cholesterol at least 10 percent more than Lipitor. Those differences should outweigh the increase in blood pressure, Dr. Feczko said.
Very few patients who take torcetrapib have a large increase in blood pressure, he said. Instead, most patients have the three to four millimeter increase, which can be managed with medication.
"There's a general minor increase in blood pressure," Dr. Feczko said.
But Dr. Steven E. Nissen, president of the American College of Cardiology, cautioned against paying down the significance of the increase. Dr. Nissen, who is overseeing the 1,190-patient clinical trial that is measuring torcetrapib's effects on plaque, said the increase was clinically meaningful and would raise the hurdles for the drug's approval.
- 182 Health