Pfizer’s one time star in its pipeline failed in a major clinical study to slow the progression of atherosclerosis – the furring of arteries – and simultaneously raised blood pressure, according to the full results from a 1,188-patient trial released early by The New England Journal of Medicine (March 26) and presented yesterday at the American College of Cardiology meeting.

In the study, 1,188 coronary heart disease patients received Pfizer’s multi-billion-dollar lipid-modifier Lipitor (atorvastatin) to lower levels of bad low-density lipoprotein cholesterol, following which they were randomly assigned to receive either Lipitor alone or Lipitor plus torcetrapib – a compound that had been billed as a potential blockbuster because of its ability to boost levels of the cardioprotective high-density lipoprotein cholesterol.

After 2 years, researchers did find a significant 61% increase in HDL-c and a 20% reduction in LDL-c. However, there was also a concomitant increase of 4.6mmHg in systolic blood pressure amongst patients given torcetrapib, and the boost to HDL-c appeared not to translate to a positive effect on heart health, with absolutely no benefit on the progression of atherosclerosis versus the group given Lipitor alone.

Whether there is hope for further entrants in this class remains to be seen, and certainly the researchers are keeping an open mind, concluding the abstract with the words: “The lack of efficacy may be related to the mechanism of action of this drug class or to molecule-specific adverse effects.” Both Merck & Co and Roche will be hoping the findings are exclusively torcetrapib’s, with their offerings MK-0859 and R-1658 currently in early-stage development.

But positive data for Lipitor

Pfizer tried to weather the effects of the release of these full data for torcetrapib by instead putting a positive spin on the results for Lipitor, currently the biggest drug in the world with annual sales in the region of $12 billion, noting that the compound clearly halted atherosclerosis in both patients with coronary heart disease and those with familial hypercholesterolaemia. “From a clinical perspective, what is remarkable in these studies is that Lipitor was able to stop the progression of disease, including the most difficult to treat FH patients studied in RADIANCE 1,” said Professor John Kastelein, lead investigator for two of the trials, and professor of medicine and chairman of vascular medicine at the Academic Medical Center in Amsterdam.

Significantly, Pfizer also announced yesterday data from two landmark clinical studies showing Lipitor 10 mg resulted in a significant 61% reduction in stroke in patients with type 2 diabetes and metabolic syndrome but without heart disease. In a separate study, patients who had suffered a recurrent stroke or mini-stroke during the trial had a significant 53% reduction in the risk of major coronary events (death from cardiac causes, heart attack, or resuscitation after cardiac arrest) with Lipitor 80 mg.

This is certainly good news for a drug that is battling generic manufacturers eager to get a foothold in this very significant marketplace. Pfizer, meantime, is looking for alternative markets and indications for its number one drug and, most recently, won US Food and Drug Administration approval for Lipitor to reduce the risk of non-fatal heart attacks, fatal and non-fatal strokes, certain types of heart surgery, hospitalisation for heart failure, and chest pain in patients with heart disease.