Clinical trials of Pfizer’s new cholesterol drug torcetrapib have confirmed its effectiveness in boosting protective high-density lipoprotein (HDL) cholesterol, but also reveal a worrying tendency to increase blood pressure in patients.
The world's number one drugmaker is developing torcetrapib as a combination therapy with its $12 billion Lipitor (atorvastatin) brand, which acts primarily by reducing levels of harmful low-density lipoprotein (LDL) cholesterol.
By combining the two compounds, Pfizer is hoping to develop a product that will not only be extremely effective in treating lipid disorders and preventing cardiovascular disease, but also defend and extend its Lipitor franchise in the face of competition from new combination treatments such as Merck & Cio/Schering-Plough’s Vytorin (simvastatin and ezetimibe) and, potentially, generic rivals.
Pfizer presented three torcetrapib/atorvastatin studies at the American College of Cardiology in Atlanta yesterday, all part of its $800 million, 25,000-patient clinical programme currently underway around the world.
In the first analysis, Pfizer found evidence that each increase of 1mg/dl of HDL was associated with a 2% reduction in risk of heart attack or stroke, supporting the hypothesis that it will work well alongside atorvastatin. The second found that patients who took torcetrapib in the morning had a higher increase in HDL levels than those who took it in the evening, which ties in with the view that this type of drug (a CETP inhibitor) should be dosed early in the day.
Finally, in the third study, patients taking both torcetrapib and Lipitor had increases in the size of HDL and LDL particles. It has been suggested that larger particles are less likely to contribute to plaque buildup. However, the third study also found that patients taking torcetrapib 60mg with Lipitor experienced a small increase in systolic blood pressure of about 2mmHg.
Pfizer said most cases of increased blood pressure occurred in patients who already had lower blood pressure on enrollment. But the concern is that the side effect, which has been seen in earlier studies of the drug, could offset torcetrapib’s benefits in patients with cardiovascular disease. Pfizer said it would ‘further define’ the blood pressure increase in its Phase III trials programme.
Pfizer is reportedly still undecided as to whether it should torcetrapib as a stand-alone therapy as well as in combination with Lipitor, after doctors voiced concerns about being pushed into choosing the Lipitor combo over rival cholesterol-lowering compounds, including simvastatin, that are generically available and cheaper.