Pfizer’s torcetrapib results cast doubt on CETP inhibitors

pharmafile | March 30, 2007 | News story | Research and Development, Sales and Marketing Pfizer, lipid 

New data on Pfizer's ill-fated torcetrapib suggest the drug doesn't reduce arterial plaque, casting doubt on other drugs in the same class now in development.

Pfizer abandoned torcetrapib last December following concerns about raised blood pressure in patients, but Merck and Roche are continuing to develop drugs in the same CETP inhibitor class.

The drugs work by raising patients' levels of HDL or good cholesterol, which is known to help clear away plaque which builds up in arteries and causes cardiovascular disease.

But while the latest study suggests that torcetrapib is very effective in raising levels of HDL cholesterol, there is no evidence this in turn helped reduce arterial plaque.

Torcetrapib raised HDL by more than 60%, but plaque volume actually increased slightly when taken either alone or in combination with Lipitor (atorvastatin)

Moreover, torectrapib was also associated with a substantial increase in blood pressure, the side-effect which had persuaded Pfizer to abandon it late last year.

The only remaining question is whether the other CETP drugs have the same profile as torcetrapib.

At the American College of Cardiology's annual meeting, Steven Nissen, chairman of cardiovascular medicine at Cleveland Clinic, which ran the torcetrapib research, said:"It is yet to be determined if this failure represents a problem unique to torcetrapib or predicts a lack of efficacy for the entire class of similar drugs."

"Unfortunately this drug also substantially raised blood pressure and failed to slow the build-up of plaque," continued Nissen. "These findings further demonstrate the great difficulty in developing therapies to disrupt the atherosclerotic disease process."

This latest setback means the road to developing a marketable CETP inhibitor – if possible – is likely to be a long one.

Nissen said other compounds in the class should first undergo studies using imaging techniques, followed by trials, which would further delay their development.

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