MEDICAL RESEARCH Pill to fight heart disease

The new drug is expected be on the market in about four years.
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PHILADELPHIA -- A pill being developed by Pfizer markedly increases the body's good HDL cholesterol, opening the door to a new way to fight heart disease, according to a study, partly funded by the drug company, in today's New England Journal of Medicine.
The drug, torcetrapib, was effective alone or combined with Pfizer's drug Lipitor, the leading brand of "statins" that lower bad LDL cholesterol.
During the small 12-week study, led by University of Pennsylvania cholesterol expert Daniel Rader and first announced at a conference last month, six patients who received the highest daily dose of torcetrapib doubled their HDL cholesterol, which scavenges fat from the arteries and carries it to the liver for disposal.
The study did not look inside blood vessels to see whether torcetrapib actually reduced the damaging buildup of plaque.
"Increasing the HDL cholesterol level by 1 mg [per deciliter of blood] may reduce the risk of cardiovascular disease by 2 to 3 percent," H. Bryan Brewer, a cholesterol expert at the National Heart, Lung, and Blood Institute, wrote in an editorial in the journal.
"The development of drugs to increase HDL ... represents an exciting new approach to the treatment of high-risk patients with cardiovascular disease."
Significance
Drugs that control blood pressure, LDL cholesterol and blood clotting have become standard in heart disease prevention and treatment. Until now, drugs to boost HDL have eluded researchers, although high doses of niacin, a B vitamin, can be helpful, said Rader, director of Penn's Preventive Cardiovascular Medicine and Lipid Center.
"There is a huge unmet need for drugs that raise HDL," said Rader, a consultant to numerous cardiovascular drug companies, including Pfizer and Bristol-Myers Squibb, both based in New York City.
All 19 patients in the torcetrapib study had HDL cholesterol below 40 milligrams per deciliter of blood, which current guidelines consider too low.
Translating from the metric system: A milligram is equal to about one-twenty-eight-thousandth of an ounce. A liter is equal to a little over a quart of liquid, and a deciliter is one-tenth of that.
Nine of the patients also received a standard dose of Lipitor because they had LDL levels over 160 mg/dL, well above the optimal level of 100 mg/dL.
Average HDL levels increased to 47 mg/dl in the Lipitor-torcetrapib group; to 46 mg/dl in the low-dose torcetrapib group; and to 70 mg/dl -- a 106 percent increase -- in the high-dose torcetrapib group. Total cholesterol was not significantly changed in any group, but torcetrapib reduced LDL by 17 percent in the combined-therapy group.
Torcetrapib works by inhibiting a protein that transfers cholesterol from the good HDL to the bad LDL, Rader said.
Other drugs
Other drugs aimed at raising HDL are in the works, according to published studies.
One drug involves the major protein for forming HDL, called Apo-A1. A synthetic version, called Apo-A1 Milano, grew out of the discovery of a mutated protein that gave a group of Italian villagers a sort of super version of HDL. Even though they had very low levels of HDL, they had little heart disease.
Unlike torceptrapib, Apo-A1 Milano is difficult to make and must be given intravenously.
Another drug, JTT-705, which works much like torcetrapib, produced only slight HDL increases in patients who started out with normal levels.
Pfizer is now enrolling patients in the final phase of torcetrapib testing, which would put Food and Drug Administration approval and product launch about four years away, a Prudential Equity Group market report said last month.
For Pfizer, the new drug -- with or without Lipitor -- could be part of a growing line of popular cardiovascular treatments. In 2002, Lipitor had nearly $8 billion in sales, accounting for 24 percent of Pfizer's total revenues, and 54 percent of the already crowded anti-cholesterol market, industry analyses show.
This year, Lipitor sales have been further boosted by two studies (the latest appearing in today's New England Journal of Medicine) that suggested the brand is superior to Pravachol, the statin made by Bristol-Myers Squibb.