Healthy Skepticism Library item: 7048
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Publication type: Journal Article
Tanne JH.
Pfizer stops clinical trials of heart drug.
BMJ 2006 Dec 16; 333:(7581):1237
Abstract:
Pfizer, the world’s largest drug company, suddenly halted phase III clinical trials of torcetrapib on 2 December. Torcetrapib is a new agent that increases concentrations of “good” high density lipoprotein (HDL) cholesterol.
Only two days earlier, Pfizer executives had said that they hoped to ask the US Food and Drug Administration for approval next year, and the company issued a financial statement: “Company highlights torcetrapib-atorvastatin and cholesteryl ester transfer protein research as most important new development in cardiovascular medicine in years.”
Pfizer said that “in the interests of patient safety” it was stopping the clinical trials of torcetrapib (called Illuminate) because the independent data safety monitoring board found more deaths and cardiovascular events in patients taking the drug. The trials included 7500 patients who were taking a combination of torcetrapib and atorvastatin (marketed as Lipitor) and 7500 patients who were taking atorvastatin alone. There were 82 deaths in the group taking the combination, compared with 51 in the group taking atorvastatin.
The trial investigators were instructed to tell patients to stop taking the combination, and Pfizer also notified the FDA.
Torcetrapib inhibits cholesteryl ester transfer protein. In patients with low HDL cholesterol, torcetrapib markedly increased HDL cholesterol and lowered “bad” low density lipoprotein (LDL) cholesterol, in a small trial reported in the New England Journal of Medicine (2004; 350:1505-15)
Pfizer began trials of torcetrapib in combination with atorvastatin, which inhibits the production of LDL cholesterol. In October, Joseph Falco, Pfizer’s chief medical officer, said that the combination increased HDL cholesterol by 55-60% and decreased LDL cholesterol by 50-60%.
On 30 November, John LaMattina, president of Pfizer Global Research and Development, said, “We are first in class, and we intend to remain best in class in a category that has the potential to change the face of cardiovascular medicine… We believe that the net benefits of the drug-characterised by significant HDL elevation and LDL lowering versus the small elevation in blood pressure-will greatly benefit patients with [cardiovascular] risk.”
Then Philip Barter, director of the Heart Research Institute in Australia and chairman of the steering committee overseeing the Illuminate study, told Pfizer that the data safety monitoring board had found higher mortality and morbidity in the torcetrapib-atorvastatin group and recommended ending the study. Dr Barter said, “We were very surprised by the information received from the DSMB [data safety monitoring board], the only body with access to the unblinded safety data. We believed the study was coming along as expected, and this new information was totally unexpected and disappointing, given the potential benefits of the drug.”
It is not yet clear whether the problems are unique to torcetrapib or whether they occur with other drugs in the class, which are being developed by other companies. There was no suggestion the problems were related to atorvastatin.
The failure of torcetrapib is a blow to Pfizer, which has sales of about $50bn (£26bn; 38bn) a year. The company says it had invested about $800m over 15 years in developing the drug, including the expansion of its manufacturing facility in Loughbeg in Ireland. Several Pfizer drugs will come off patent in the next few years, including atorvastatin in 2010, which has sales of $13bn a year and is the world’s most prescribed drug. Before the torcetrapib failure, Pfizer had already announced restructuring plans that included reducing its US sales force by about 20%. After the announcement, its shares fell about 10%.
