November 13, 2006 09:00 ET

WelChol and Ezetimibe Combination Therapy Provides Significant LDL-C Reductions

Study Published in Current Medical Research and Opinion® Shows Combination Therapy Provides Mean LDL-C Drops of 32%

PARSIPPANY, NJ -- (MARKET WIRE) -- November 13, 2006 -- A new study found that taking WelChol® (colesevelam HCI) in combination with ezetimibe reduced LDL-C by 32%, reducing mean LDL-C levels by an additional 11% over ezetimibe monotherapy in patients with primary hypercholesterolemia (p < 0.0001). Published today in Current Medical Research and Opinion®, this is the first, randomized placebo-controlled clinical trial to evaluate WelChol in combination with ezetimibe.

The study, entitled "Lipid Lowering Effects of Colesevelam HCl in Combination with Ezetimibe," aimed to evaluate whether the combination of WelChol plus ezetimibe produces increased LDL-C lowering over ezetimibe monotherapy.

"This study emphasizes a valuable alternative to statins, with the reduction in LDL-C levels shown here similar to the results achieved with many statins at their typical starting doses," said Harold E. Bays, MD, FACP, Louisville Metabolic and Atherosclerosis Research Center Inc., Louisville, KY, and lead study investigator. "As we know, for every percentage point of reduction in LDL-C, there is a reduction in risk of developing coronary heart disease, the leading cause of death in the U.S. For people who cannot tolerate or don't want to be on a statin, this combination provides equivalent LDL-C benefits to lower statin doses."

The study also demonstrated that the combination therapy provided significant improvements in other lipid parameters. WelChol plus ezetimibe showed greater percent changes in levels of total cholesterol (p = 0.0020), non-HDL-C (p = 0.0024), apo A-I (p = 0.0036) and apo B (p = 0.0001), compared to ezetimibe monotherapy. WelChol plus ezetimibe also significantly increased levels of apo A-I versus baseline (p < 0.0001), and decreased hs-CRP versus baseline (p = 0.0301) while ezetimibe monotherapy showed no change. Additional improvements were also seen in lipoprotein ratios. The combination of WelChol plus ezetimibe resulted in 19% (8/42) vs 2% (1/43) (p = 0.0148) of subjects achieving an LDL-C target of < 100mg/dL.

About the Study

In a 10-week, multi-center, randomized, double-blind, placebo-controlled, parallel-group study, patients with primary hypercholesterolemia (defined as LDL-C greater than or equal to 130 mg/dL and triglycerides < 400 mg/dL) were evaluated to determine the efficacy and safety of WelChol when combined with ezetimibe as compared to ezetimibe monotherapy.

The study involved 86 patients between the ages of 18 and 80 at seven clinical sites across the U.S. Following a 4-8 week washout period for those patients already taking lipid-lowering therapy at screening, patients were randomized to receive either WelChol (3.8 g/day) plus ezetimibe (10 mg/day) or placebo plus ezetimibe (10 mg/day).

The primary efficacy endpoint of the study was the mean percent change in LDL-C levels from baseline at week six. Secondary endpoints included mean absolute change in LDL-C; mean absolute and percent changes in TC, HDL-C, non-HDL-C, Apo A-I, and Apo B; median absolute and percent changes in triglycerides and hs-CRP; mean absolute changes in the lipoprotein ratios LDL-C/HDL-C, TC/HDL-C, non-HDL-C/HDL-C, and Apo B/Apo A-I; and percentage of patients achieving LDL-C targets of < 100 mg/dL.

About WelChol

WelChol is indicated for LDL-C lowering and was approved by the U.S. Food and Drug Administration (FDA) for marketing in May 2000. WelChol is the top-selling branded drug in the bile acid sequestrants (BAS) class. WelChol is different from most other cholesterol-lowering drugs on the market because it is non-systemic, meaning that the body does not absorb it and it is eliminated without traveling to the liver or kidneys. Systemic medications, which include the statins, fibrates, and cholesterol absorption inhibitors, are those that are absorbed from the intestine into the bloodstream and travel throughout the body, specifically to the liver and/or kidneys.

WelChol is a prescription drug indicated alone or in combination with a statin, as an adjunct to diet and exercise for the reduction of elevated LDL cholesterol in patients with primary hypercholesterolemia (Fredrickson Type IIa) when the response to diet and exercise has been inadequate. Liver-function monitoring is not required with WelChol when used as monotherapy, and in combination with a statin, no additional liver-function monitoring is required beyond that for the prescribed statin alone.

In clinical trials with patients with primary hypercholesterolemia, when WelChol was given alone in addition to a low-fat diet and exercise, it was shown to reduce LDL cholesterol by an average of 15 to 18%.

When WelChol is given in combination with a statin, the combination can lower cholesterol levels more effectively than using either therapy alone. In pivotal studies where WelChol was taken with a statin, WelChol 3.8g provided up to an additional mean 16% (32 mg/dL) reduction in LDL cholesterol. WelChol is the only non-systemic cholesterol-lowering agent approved by the FDA for combination with a statin. WelChol can be used in combination with any dose of any statin.

Because WelChol is engineered for affinity, specificity and high capacity bile acid binding, it may have a lower drug-drug interaction potential than conventional bile acid sequestrants. It has been studied with four commonly prescribed statins -- Lipitor® (atorvastatin calcium), Zocor® (simvastatin), Pravachol® (pravastatin sodium) and Mevacor® (lovastatin). Additionally, WelChol has been studied with fenofibrate and had no effect on the bioavailability on fenofibrate. Like most prescription drugs, WelChol has not been studied in combination with all medications or supplements. Patients should always tell their doctor about all medications and supplements they are taking before starting any new therapy, including WelChol.

WelChol is not for everyone, especially those with bowel blockage. Caution should be exercised when treating patients who have trouble swallowing or severe stomach or intestinal problems. Side effects may include constipation, indigestion and gas. WelChol, either alone or in combination with a statin or fenofibrate, has not been shown to prevent heart disease or heart attacks.

WelChol is only indicated for the reduction of LDL-C either alone or in combination with a statin in patients with primary hypercholesterolemia. WelChol has also been studied in combination with fenofibrate in patients with mixed dyslipidemia (Fredrickson Type II B), and provided additional LDL-C reductions in these patients when added to a stable fenofibrate regimen. Additionally, WelChol has demonstrated beneficial effects on other lipid parameters such as HDL-C, APO-B , and hs-CRP levels in other clinical trials. However, WelChol is not indicated for use in treatment of these lipid parameters or in patients with mixed dyslipidemia.

For more information on WelChol, call 877-4-DSPROD (877-431-7763), or go to the WelChol web site at www.WelChol.com.

About Daiichi Sankyo, Inc.

Daiichi Sankyo, Inc. was established in April of 2006 as the U.S. subsidiary of Japanese pharmaceutical company Daiichi Sankyo Co., Ltd. The company was formed by the merger of U.S. entities Sankyo Pharma Inc., Daiichi Pharmaceutical Corporation and Daiichi Medical Research. Headquartered in Parsippany, New Jersey, the company's strategic focus is on cardiovascular diseases. Research and development of new therapies is also focused in the areas of glucose metabolic disorders, infectious diseases, cancer, immunology and bone and joint diseases. Daiichi Sankyo's portfolio includes BENICAR® (olmesartan medoxomil) and BENICAR HCT® (olmesartan medoxomil/hydrochlorothiazide), the fastest growing angiotensin receptor blocker on the market, and WelChol®, the number one branded bile acid sequestrant.(1) For more information, please visit www.daiichisankyo-us.com.

Trademarks not owned by Daiichi Sankyo, Inc., are the property of their respective owners.

(1) Data are representing May 2002 - February 2006 from IMS Health. National Prescription Audit, February 2006.