New Class of Drug Dramatically Lifts HDL Cholesterol by 139%

A new cholesterol experimental drug by Merck & Co., from the same class as the one that failed for Pfizer, had dramatic results in a small clinical trial, raising HDL by 39% and lowering LDL by 40% without the safety problems that killed 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%.

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

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

Even with its impressive effects on LDL and HDL cholesterol, Bloomfield said believes that the FDA is unlikely to approve MK-859 until such studies are completed.

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.

Source: Diabetes In Control: Presented Oct. 11, 2007 at the Drugs Affecting Lipid Metabolism meeting in New York.