Investigational Drug Dramatically Lifts HDL Cholesterol

By Ransdell Pierson and Bill Berkrot

NEW YORK (Reuters) Oct 05 - An experimental Merck & Co. cholesterol drug from the same class as one that failed for Pfizer Inc had dramatic results in a small clinical trial, without the safety problems that doomed the Pfizer product.

The drugs are inhibitors of the cholesteryl ester transfer protein (CETP), which regulates plasma HDL cholesterol concentration. At the second-highest dose tested in the 8-week trial, the Merck drug MK-859 raised levels of HDL by 139% and cut levels of LDL cholesterol by 40%, according to data presented on Thursday at the Drugs Affecting Lipid Metabolism meeting in New York.

The Merck drug did not cause a rise in blood pressure, a side effect that had dogged Pfizer's now-abandoned torcetrapib and which many believe caused increased deaths associated with it.

"As hard as we looked, we couldn't find any increase in blood pressure," said Daniel Bloomfield, a senior Merck research official who helped lead the study of MK-859.

"The data really point out you can inhibit CETP with MK-859, and substantially reduce LDL and increase HDL, and importantly not raise blood pressure," he said.

Four doses of the drug, 10 mg, 40 mg, 150 mg and 300 mg, were tested against placebo. "The data suggest any dose would be safe to go forward with" in any future late-stage trials, Bloomfield said.

The incidence of side effects among patients taking MK-859, whatever the dose, was similar to those seen among patients given placebos.

However, Bloomfield cautioned that his drug's true safety would not be known until it goes through much larger studies, which typically take 4 to 7 years and focus on the risk of heart attacks and death.

Despite its impressive effects on LDL and HDL cholesterol, Bloomfield said Merck believes U.S. regulators are unlikely to approve MK-859 until such studies are completed.

Merck's trial of MK-859 involved 589 patients with high levels of LDL cholesterol and/or low levels of HDL.

HDL levels rose by 44% and 86%, respectively, among patients taking 10 mg and 40 mg doses of MK-859, while results seen with the highest 300 mg dose were similar to those of the 150 mg group.

Levels of LDL cholesterol fell 16% and 27%, respectively, among those receiving the two smallest doses of the drug, and fell 39% in the highest-dose group.

HDL levels rose only 4% in the placebo group, while LDL levels rose 2%.

The Merck drug was also tested at all doses in combination with 20 mg doses of Lipitor. The combination did not have any additional impact on raising HDL, but it magnified the impact on LDL, lowering it as much as 68% at the highest dose of MRK-859.

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