Merck's Investigational Lipid-Modifier, CORDAPTIVE™ , Positively Affected Key Lipid Parameters With Less Flushing, In Data from Phase III Study

Business Wire, Sept 2, 2007

WHITEHOUSE STATION, N.J. -- Merck & Co., Inc. announced today Phase III clinical study results with CORDAPTIVE(TM) (ER niacin/ laropiprant), an investigational compound containing Merck-developed extended-release niacin and laropiprant - a novel flushing pathway inhibitor, in which CORDAPTIVE reduced LDL-cholesterol (LDL-C) levels, increased HDL-cholesterol (HDL-C) levels and reduced triglyceride levels compared to placebo. Patients treated with CORDAPTIVE also reported significantly less flushing compared to those patients treated with extended-release niacin alone. CORDAPTIVE was administered as 1- and 2- gram doses alone or added to ongoing statin therapy in patients with dyslipidemia. These results were presented today at the 2007 European Society of Cardiology (ESC) Annual Congress in Vienna, Austria.

Across weeks 12 to 24 of the study, 2 grams (two 1-gram tablets) of CORDAPTIVE produced significant percent changes from baseline in LDL-C levels (-18 percent), HDL-C levels (20 percent) and triglyceride levels (-26 percent) relative to placebo. In addition, patients treated with CORDAPTIVE reported significantly less flushing both at the initiation of therapy and during maintenance therapy, compared to patients on extended-release niacin alone. In the study, a 1 gram tablet of CORDAPTIVE contained 1 gram of extended-release niacin and 20 mg of laropiprant. All of the comparative lipid efficacy and flushing side effect results presented from this study were statistically significant (p<0.001).

"Many LDL-C-lowering drugs have been shown to reduce the risk of heart attacks and stroke; however, the majority of these patients continue to be at risk for cardiovascular events. Niacin has been shown in previous outcome studies to reduce the risk of cardiovascular events, but its use has been limited as a result of the flushing side effect," said Anders Olsson, MD, Professor at the Faculty of Health Sciences of Linkoping University in Sweden, and a study investigator. "The results of this Phase III study support the development of the investigational compound CORDAPTIVE, which may result in fewer patients discontinuing therapy due to flushing."

About the study

The study was a double-blind, randomized trial that evaluated the lipid efficacy and flushing profile of CORDAPTIVE, as monotherapy or combined with a statin, in 1,613 patients with dyslipidemia (primary hypercholesterolemia or mixed dyslipidemia).

Patients - around 65 percent of whom were already on statin therapy - were initiated at either 1 gram of CORDAPTIVE per day (n=800), 1 gram of extended-release niacin alone per day (n=543), or placebo (n=270). After four weeks, patients in the group being treated with CORDAPTIVE and the group being treated with extended-release niacin doubled their respective doses to 2 grams per day for an additional 20 weeks.

The co-primary endpoints were the effects of 2 grams of CORDAPTIVE versus placebo on percent changes in LDL-C across weeks 12 to 24, and of 1 gram of CORDAPTIVE versus extended-release niacin on flushing symptom severity during the first week of treatment. Key secondary endpoints included the effects of 2 grams of CORDAPTIVE versus placebo on HDL-C levels, triglyceride levels and other lipid parameters, and the flushing frequency and intensity of 2 grams of CORDAPTIVE compared to extended-release niacin alone.

In the study, patients who advanced to 2 grams of CORDAPTIVE reduced their LDL-C levels from baseline by an average of 19 percent (versus a reduction of 0.5 percent with placebo), raised their HDL-C levels by an average of 19 percent (versus a reduction of 1.2 percent with placebo), and reduced their triglyceride levels by an average of 22 percent (versus an increase of 3.6 percent with placebo). The 2-gram dose of CORDAPTIVE also significantly reduced both "non-HDL-C" (another measure of lipids which includes a broader spectrum of atherogenic lipoproteins) and Apolipoprotein B (also called Apo B, a component of LDL-C), and raised Apolipoprotein A-I (also called Apo A-I, a component of HDL-C). These effects were observed from weeks 12 to 24 and occurred irrespective of concomitant statin therapy.

As measured by the Global Flushing Severity Score (GFSS), 69 percent of patients treated with 1 gram of CORDAPTIVE reported either no flushing symptoms or mild flushing symptoms during the first week of treatment, compared to 44 percent of those who received extended-release niacin alone. Nearly half of the patients in the extended-release niacin group (49 percent) reported moderate or greater flushing symptoms during week 1, compared to 27 percent treated with CORDAPTIVE. By week 24, the frequency of moderate or greater flushing was 0.7 days/week among those treated with 2 grams of extended-release niacin, versus 0.2 days/week for patients taking 2 grams of CORDAPTIVE or a placebo. More than twice as many patients on extended-release niacin discontinued treatment because of flushing than patients taking CORDAPTIVE (22 percent versus 10 percent).