Abbott and AstraZeneca announced a collaboration to co-develop and market a combination treatment that will target all three important blood lipids - LDL-C "bad" cholesterol, HDL-C "good" cholesterol, and triglycerides - in one single pill as part of a comprehensive treatment regimen.

Under the agreement, the companies will initiate two parallel programs: a Crestor (rosuvastatin calcium)/TriCor (fenofibrate tablets) fixed-dose combination and a Crestor/ABT-335 combination. ABT-335 is Abbott's proprietary next-generation fenofibrate currently in Phase III clinical trials.

One of the two programmes will be selected for final development and commercialization based upon data generated from the initial studies.

According to the American Heart Association (AHA), more than 38 million Americans have complex lipid disease and may benefit from this new combination. The cholesterol market is currently valued at $17 billion. Combination therapy makes up 15 percent and represents the fastest-growing segment of the overall cholesterol management market.

"Treatment guidelines emphasize the need to manage three important lipids by lowering bad cholesterol and triglycerides and raising good cholesterol. Increasing evidence shows that addressing these three key lipid targets helps to protect patients from heart disease," said Eugene Sun, M.D., vice president, Global Pharmaceutical Clinical Development, Abbott. "This collaboration has the potential to provide physicians and patients with the first statin and fibrate combination in a single pill to comprehensively manage lipids."

"We're excited by the opportunity this deal presents to serve an important area of patient need," said Tony Zook, executive vice president, North America, AstraZeneca. "This represents an important further step in broadening the full, long-term potential of CRESTOR for the treatment of lipid disorders."

TriCor and Crestor are both lipid-regulating agents available within the cholesterol management market. TriCor and ABT-335 are part of a class of medications called fibrates. TriCor has been shown to predominantly raise HDL-C and reduce triglycerides, a form of fat or lipid obtained through food sources. It also is effective at reducing elevated LDL-C. Crestor is part of a class of medications called statins, which have been shown to predominantly reduce LDL-C. This combination would potentially address LDL-C, HDL-C and triglycerides simultaneously with a combined fibrate and statin medication in a single pill, and is thus expected to lead to improved compliance and outcomes.

The overall intention of the agreement is for the two companies broadly to share development costs and profits over the duration of the collaboration. Abbott will execute the clinical trial program and be responsible for regulatory registration of the new combination therapy. AstraZeneca will hold the New Drug Application (NDA). Following successful completion of the clinical program, a regulatory application for the new combination therapy is targeted for submission in 2009.

"Rigorous clinical study of these two drugs in combination to document their safety and efficacy is important for patients and could produce an important new comprehensive lipid treatment tool for physicians," said Peter H. Jones, M.D., associate professor of medicine, Baylor College of Medicine, Houston.

Presently, health care professionals are advised to carefully weigh the risks and benefits of using fibrates and statin drugs in combination.

The effectiveness of the agreement is subject to satisfying certain conditions, including obtaining customary Hart-Scott-Rodino antitrust clearance.

Abbott is currently evaluating ABT-335 as a co-administered therapy with three other on-market statins, including Crestor.

Cardiovascular disease is the leading cause of death in the United States. More than 100 million Americans have dyslipidemia. More than 38 million American adults have LDL-C, HDL-C and triglycerides at levels that represent a major risk factor for coronary artery disease and stroke. Recently, treatment guidelines endorsed by the National Cholesterol Education Panel (NCEP), the American College of Cardiology (ACC), AHA and others have called for more aggressive treatment of lipids, including a lower LDL-C goal for many patients, as well as more aggressive treatment of HDL-C and triglycerides. In addition to healthy lifestyle changes, a certain percentage of patients will require more than one medication to meet these goals, which the proposed combination could address.

Cholesterol is a natural, waxy, fat-like substance found in the body. There are two sources of cholesterol in the body. Some cholesterol is made in the liver, and the rest comes primarily from animal products that are eaten, such as meats, poultry and cheese.

Elevated cholesterol can lead to heart attacks and other cardiovascular-related problems. Unlike high LDL-C, which has been directly linked to increased heart disease risk, a high HDL-C level is considered "good" because HDL-C can often help reduce risk of heart disease. Triglycerides are another type of fat in the bloodstream. The NCEP guidelines say that elevated triglycerides also are an independent risk factor for heart disease.


Crestor (rosuvastatin calcium) is a once-daily, lipid-lowering agent prescription medication for use as an adjunct to diet in the treatment of various lipid disorders including primary hypercholesterolemia, mixed dyslipidemia and isolated hypertriglyceridemia. It is a member of the statin (HMG-CoA reductase inhibitors) class of drug therapy. Crestor has not been determined to prevent heart disease, heart attacks, or strokes. For patients with hypercholesterolemia and mixed dyslipidemia, the usual recommended starting dose of Crestor is 10 mg. However, initiation of therapy with 5 mg once daily should be considered for patients requiring less aggressive LDL-C reductions or who have predisposing factors for myopathy, and for special populations such as patients taking cyclosporine, Asian patients, and patients with severe renal insufficiency. For patients with marked hypercholesterolemia (LDL-C>190 mg/dL) and aggressive lipid targets, a 20-mg starting dose may be considered. AstraZeneca licensed worldwide rights to Crestor from the Japanese pharmaceutical company Shionogi & Co., Ltd.

TriCor (fenofibrate tablets) is a lipid-lowering agent used to treat abnormal lipid levels in the bloodstream, including cholesterol and triglycerides. TriCor is a once-daily treatment available in 145 mg and 48 mg tablets that can be taken with or without food.

TriCor, in addition to appropriate diet, is used to treat adults with high cholesterol, with or without elevated triglycerides (Fredrickson types IIa, IIb). TriCor reduces elevated LDL-C ("bad" cholesterol), total cholesterol, triglycerides and apolipoprotein B, and increases HDL-C ("good" cholesterol). The effect of TriCor on cardiovascular morbidity and mortality and noncardiovascular mortality has not been established. Abbott markets TriCor in the U.S. through an agreement with Solvay Pharmaceuticals. ABT-335 development is co-funded by Solvay Pharmaceuticals.

TriCor, in addition to appropriate diet, is also used to treat adults with high triglycerides (Fredrickson types IV and V). Excessive body weight, drinking alcohol, diseases such as diabetes and hypothyroidism, and various drugs can contribute to high triglyceride levels, and these should be assessed before a patient is prescribed TriCor tablets. TriCor should only be prescribed after reasonable attempts to modify lipid profile with diet modification, exercise and decreased alcohol consumption have failed. It is important for patients to stay on a diet restricted in saturated fat and cholesterol while taking TriCor.