New study demonstrates co-administration

October 15, 2004

Parsippany, NJ (October 15, 2004) - The results of a new study, published in the September 2004 issue of Clinical Pharmacokinetics, showed that no significant drug-drug interaction occurred when WelChol® (colesevelam HCI) was co-administered with TriCor® (fenofibrate tablets).

The findings were consistent across two different dosing options of the two cholesterol-lowering therapies -- when WelChol, a bile acid sequestrant (BAS), was given at the same time as TriCor, a fibrate, or when TriCor was given four hours prior to WelChol.

Meeting the National Cholesterol Education Program (NCEP) guidelines for optimal cholesterol levels can be elusive when patients have high LDL (bad) cholesterol levels, or low HDL (good) cholesterol levels, or high triglycerides, or any combination of these. Therefore, many physicians may prescribe more than one cholesterol-lowering therapy. For example, physicians may use WelChol to lower LDL (bad) cholesterol levels, or TriCor to primarily lower trigylcerides. However, it is currently recommended in the TriCor label that TriCor be taken at least one hour before, or four to six hours after a BAS because of the potential for drug interactions.

"Obviously the complexity of this dosing schedule can create difficulties for patients trying to comply with the treatment regimen," said Michael R. Jones, Ph.D., lead investigator of the study and Director, Phase IV Research, Sankyo Pharma Inc. "Although WelChol is a BAS, it offers a unique molecular approach different from that of earlier BAS therapies. As this study has found, WelChol and TriCor can be taken together without a concern of a significant drug-drug interaction."

About the Study
The open-label, three-way crossover drug interaction study involved 30 healthy volunteers between the ages of 19 and 50 years. Every participant received, in random order, three different treatment regimens, consisting of WelChol (6 tablets at 625 mg) and TriCor (1 tablet at 160 mg), over 27 days: A) WelChol and TriCor with a standard low-fat breakfast; B) TriCor with a standard low-fat breakfast, followed by WelChol four hours later with a standard low-fat lunch; and, C) TriCor with a standard low-fat breakfast. Each treatment regimen was separated by a 10-day wash-out period. After each dosing, blood levels of fenofibric acid (the active metabolite of TriCor), were followed for 120 hours.

As was expected, WelChol had no significant effect on the bioavailability of TriCor, as assessed by blood levels of the active metabolite (fenofibric acid) when TriCor was administered four hours prior to WelChol. Bioavailability is the extent to which a drug becomes available to the body.

Additionally, when the two drugs were co-administered at the same time, WelChol had no significant effect on the total drug exposure of fenofibric acid. However, there was an approximate 20 percent reduction in the Cmax (maximum plasma concentration) of fenofibric acid. This is unlikely to be clinically relevant because it was smaller than the variability of Cmax when TriCor was taken alone.

About WelChol
WelChol, a non-systemic lipid-lowering agent approved by the U.S. Food and Drug Administration (FDA) for marketing in May 2000, is the top selling branded drug in the bile acid sequestrant class (BAS).

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, kidneys or any other target organs. Systemic medications, which include the statin class, are those that are absorbed from the intestine into the bloodstream and travel throughout the body. WelChol is indicated, alone or in combination with a statin, as an adjunct to diet and exercise for the reduction of elevated LDL (bad) 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, when WelChol was given alone in addition to a low-fat diet and exercise, it was shown to reduce LDL (bad) cholesterol by an average of 15 to 18 percent.

When WelChol is given in combination with a statin, the combination can more dramatically lower cholesterol levels than using either therapy alone. In a study where WelChol was taken with Zocor® (a statin), WelChol 3.8 g provided a 16 percent (32 mg/dL) additional average LDL cholesterol reduction in combination therapy beyond that of Zocor 10 mg alone. WelChol is the only non-systemic cholesterol-lowering agent FDA approved to be used in combination with any dose of any statin. It has been studied with three commonly prescribed statins - Lipitor,® Zocor and Mevacor®.

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 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.
-end-
For more information on WelChol, call 877-4-SANKYO (877-472-6596), or go to the WelChol web site at www.WelChol.com.

About Sankyo Pharma
Sankyo Pharma Inc. is dedicated to developing and marketing important pharmaceutical products for the U.S. market. A national sales force of 530 representatives promotes WelChol, and they are supported by dedicated managed care personnel. Sankyo Pharma also markets medications for the treatment of hypertension with its co-promote partner Forest Laboratories, Inc.

Sankyo Pharma launched WelChol®, a non-systemic lipid-lowering agent, in September 2000. Currently, WelChol is the number one prescribed branded agent in its category with 2003 sales in excess of $100 million dollars. Sankyo Pharma's parent company, Sankyo Co. Ltd. of Tokyo, is one of Japan's largest pharmaceutical companies, with annual worldwide sales of $4.5 billion. Sankyo has a long history of discovering new classes of drugs, including the statin class of lipid-lowering drugs, with its discovery of the first statin, mevastatin, and the co-discovery of lovastatin, the first statin to be marketed. Additionally, Sankyo discovered, co-developed and manufactures pravastatin sodium.

Please see package insert for full prescribing information

Zocor® (simvastatin) and Mevacor® (lovastatin) are registered trademarks of Merck & Co., Inc.
Lipitor® (atorvastatin calcium) is a registered trademark of Pfizer Inc.
TriCor® (fenofibrate tablets) is a registered trademark of Abbott Laboratories.
WelChol® (colesevelam HCI) is a registered trademark of Sankyo Pharma Inc.

Hill and Knowlton

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