Researchers shed a little more light on what went so badly wrong with Pfizer’s torcetrapib (pictured) during a presentation at the American Heart Association’s confab in Orlando.
Besides boosting HDL, or good, cholesterol levels, torcetrapib sharply increased risks of death during trials. Pfizer spiked the mammoth drug-development program last December after torcetrapib spurred an increase in deaths and heart problems in patients taking the drug in combination with Lipitor. The study of 15,000 patients, overseen by the Heart Research Institute in Sydney, saw risk of death increase by 58% and risks of heart attack or other heart problems increase by 25% in the combination therapy versus Lipitor alone.
What went haywire? Dr. Philip Barter, the institute’s lead researcher, suggested that torcetrapib boosted aldosterone, a hormone involved in the regulation of blood pressure. But he cautioned that still more research must be done to explain how that could have made the drug so unsafe.
Merck and Roche have been developing similar drugs, so-called CETP inhibitors, and had been awaiting details about torcetrapib. Steven Nissen, head of cardiovascular medicine at the Cleveland Clinic, told Bloomberg that torcetrapib “has a bizarre, off-target toxicity that caused it to produce harm and concealed the benefit” of raising good cholesterol. “Now there’s a race on,” he said. “We can get back on the horse and try again.”
An editorial in today’s New England Journal of Medicine warned against reading too much into the torcetrapib’s failure: “In any case, it is premature to announce the death of CETP inhibitors on the basis of the torcetrapib experience alone.”
Steve Ryder, Pfizer’s head of torcetrapib research and development, told Dow Jones Newswires: “There are many questions that still remain.”
And that burden will hang over the other experimental drugs that aim to raise good cholesterol as torcetrapib did. “The whole fiasco with torcetrapib means that we’re going to have to be even more cautious with any of its cousins before they come to market,” Sharonne Hayes, a cardiologist at the Mayo Clinic, told Bloomberg. “It’s going to be a much higher bar.”
