Pfizer discontinues phase-3 trial of torcetrapib

Independent Data Safety Monitoring Board recommended Pfizer terminate ILLUMINATE study due to mortality, CV events.

Pfizer has terminated its Lipid Level Management to Understand its Impact in Atherosclerotic Events trial, according to an FDA press release.

Pfizer stopped the phase 3 ILLUMINATE trial and must inform all participants to stop receiving torcetrapib, which inhibits cholesteryl ester transfer protein.

“Although the [Data Safety Monitoring Board] information we received today was both surprising and disappointing, our focus is on the best interests of patients and making sure all this information is communicated to appropriate medical and regulatory authorities as quickly as possible,” Jeffrey B. Kindler, Pfizer’s chief executive office, said in a company press release.

Increased mortality

The DSMB recommended termination because of an imbalance of mortality and cardiovascular events.

“Based on all the evidence we have seen regarding torcetrapib and in light of previous study results, we were surprised by the information received from the DSMB, the only body with access to the unblinded safety data,” said Philip Barter, MD, PhD, director of the Heart Research Institute, Camperdown, Australia, and chairman of the steering committee overseeing the ILLUMINATE trial, in a press release. “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.”

Steven Nissen, MD, department chairman of CV medicine at the Cleveland Clinic and president of the American College of Cardiology, said the DSMB and Pfizer handled the situation properly.

The researchers planned to announce trial results at the American Heart Association Scientific Sessions 2006 in November. However, the AHA could not allow the results to be presented because the embargo was broken, according to a Pfizer representative.

The New England Journal of Medicine published results from a torcetrapib study in 2004. Brousseau and colleagues found that torcetrapib increased HDL and decreased LDL when taken alone or in combination with a statin. Patients who received 120 mg/day of torcetrapib and atorvastatin (Lipitor, Pfizer) experienced a 61% increase in plasma concentrations of HDL (P<.001). Patients who received only torcetrapib experienced a 46% increase in HDL (P=.001). In addition, patients who received torcetrapib and atorvastatin experienced a 17% decrease in HDL, according to the journal article.

Atorvastatin was used as a comparator in ILLUMINATE because it is the most studied statin in reducing CV outcomes.

Pfizer has two other similar compounds in very early-stage development, according to Pfizer representative. In addition, Merck and Roche also have similar drugs in the pipeline, according to Nissen. – by Lauren Riley

For more information:

• Brousseau ME, Schaefer EJ, Wolfe ML, et al. Effects of an inhibitor of cholesteryl ester transfer protein on HDL cholesterol. N Engl J Med. 2004;350:1505-1515.