New York, NY - Pfizer has backed off a controversial decision to sell torcetrapib only in combination with atorvastatin (Lipitor), another Pfizer drug. The company now plans to make torcetrapib, a promising cholesteryl ester transfer protein (CETP) inhibitor that raises HDL-cholesterol levels, available as a standalone therapy, allowing clinicians to use the drug with statins other than atorvastatin.

The initial decision drew intense criticism because many doctors believed the move was designed to protect atorvastatin, a drug that loses patent protection in 2010 and currently has sales of almost $7.4 billion. Many argued that torcetrapib should be made available on its own, leaving physicians the option of prescribing whatever statin they wish with the novel HDL-raising drug.

Dr Steven Nissen (Cleveland Clinic, OH), who commented Pfizer's decision for heartwire, said he was pleased the company has altered its course.

"I think many patients will be fine getting the combination of torcetrapib and atorvastatin, but the availability of the drug alone ensures that everybody who needs to be treated with an HDL-raising drug can be treated," he said. "By making it available alone, it allows us to mix and match with other statins to treat patients who might tolerate only one statin. We occasionally see patients who will have side effects or adverse symptoms on one agent but can tolerate another. What this does for us is that it allows physicians and patients to have access to torcetrapib regardless of the statin that is preferred in that patient."

In an interview with Pfizer spokesperson Stephen Lederer last year, Lederer told heartwire that selling the two drugs together in one tablet was the quickest and safest way for the company to get the drug to the market.

However, aside from complaints from clinicians, including an editorial published June 23, 2005 issue of the New England Journal of Medicine by Dr Jerry Avorn (Harvard Medical School, Boston, MA) that claimed Pfizer's development strategy for torcetrapib was just a way of protecting sales of Lipitor once its patent expires, the company would have faced legal hurdles by tying the drug to atorvastatin. As reported in the July 26, 2006 issue of the New York Times, Pfizer's plan to bundle the two drugs faced commercial and legal challenges, including questions about whether the decision violated antitrust laws [1]. Moreover, with the emergence of generic statins, atorvastatin is losing market share, and the company risked damaging future sales of the drug by tying it to atorvastatin, the Times reports.

Nissen said that he was pleased that the company responded to the criticism. "I think a good company will listen to its critics and, when the critics are making sense, will adapt its policies appropriately. That is what they did, and I think they should be applauded for doing so," he said.

Nissen noted, however, that one important caveat remains: whether the drug actually works. He told heartwire there is still some controversy as to whether torcetrapib's mechanism of raising HDL produces functional HDL cholesterol. To address these questions, Nissen is currently leading the ILLUSTRATE study, 1200-person trial comparing atorvastatin/torcetrapib combination therapy with atorvastatin alone in preventing progression of coronary atherosclerosis as measured by IVUS in coronary heart disease patients. The major end point trial for torcetrapib is ILLUMINATE, a 15 000-patient trial studying the effects of torcetrapib/atorvastatin vs atorvastatin alone on the occurrence of major cardiovascular events in subjects with coronary heart disease or risk equivalents. Results of that study are not expected for another four or five years.

According to the New York Times, Pfizer plans to submit an application to the Food and Drug Administration (FDA) to sell the combination tablet in 2007 based on the results of the ILLUSTRATE trial. If the drug is shown to be safe and effective, an approval could be expected in 2008. Pfizer told the Times the company plans to submit applications this September for early-stage clinical trials that would combine torcetrapib with statins other than Lipitor.

"I'm glad that we'll have choice," said Nissen. "I think it's the right decision, and I hope that we can move forward so that there is very little of a time gap between the availability of the combination and the standalone therapies."