By Timothy Tankosic, M.D.

The opportunity
Although precise definitions of metabolic syndrome vary, all include the cluster within an individual of risk factors related to:

• Cardiovascular abnormalities -- dyslipidemias (and consequent atherogenesis) and hypertension;
• Diabetic or prediabetic states -- particularly insulin resistance (which is considered to be an important causative factor); and
• Obesity -- particularly abdominal obesity (which is considered to be an important causative factor).

Other characteristics of metabolic syndrome have been identified (e.g., pro-inflammatory and pro-thrombotic states), and still others are under study.

Metabolic syndrome has a great impact on morbidity and mortality. It is estimated that almost 25% of the adult population in the U.S., including as many as 60% of obese individuals, qualify for a diagnosis of metabolic syndrome. Clinically, it manifests as significant increases in the risk of developing cardiovascular disease (by at least 2-fold and possibly up to 4-fold) and great increases in the risk of developing diabetes (by up to 25-fold). The current underserved market and projections of increasing prevalence of constituent conditions of metabolic syndrome point to a large emerging market for drugs for its prevention and treatment:

• The number of people with type 2 diabetes will rise from nearly 200 million in 2005 to 333 million by 2025;
• About 1/3 of adults in the U.S. are obese; the prevalence of obesity in U.S. adults has increased>30% during the last 15 years and is increasing in Europe; and
• The number of people in Western nations with total cholesterol>200mg/dL is currently rising at an estimated 1% per year.

Drug development: new and already approved drugs
Metabolic syndrome is readily treatable, and drug developers are hotly pursuing broader indications of approved drugs and the development of new drugs for its treatment. [Diagnostics developers are following suit as they work to identify new markers and develop in vitro tests for risk prediction, predisposition, drug responsiveness, and other applications.] Considerations for new drug development include therapies, which directly address the core abnormalities of metabolic syndrome and provide multiple mechanisms of action for the benefit of the largest number of patients. Even drug development for chronic conditions unrelated to metabolic syndrome has been affected, as R&D consider the potential of developmental agents to cause adverse affects associated with metabolic syndrome and attempt to develop metabolism-friendly drugs.

Drug developers are testing approved drugs for metabolic syndrome based on known mechanisms of action (e.g., statins demonstrate anti-inflammatory activity; peroxisome proliferator-activated receptor, or PPAR activators, also demonstrate anti-lipid activity) and on clinical observations (e.g., atorvastatin is now indicated for use in patients who have normal cholesterol levels but other heart disease risk factors). Approved statins and PPAR activators, and if approved, the anti-obesity and -smoking drug, Acomplia™ (rimonabant, Sanofi-Aventis) are expected to compete in the metabolic syndrome market. Large controlled studies demonstrating efficacy will be a critical component for marketing efforts. [Pfizer's patent on Lipitor® (atorvastatin) was upheld (until November 2011) by the U.K. High Court of Justice in October.]

Table 1 below lists examples of drugs with potential application in the treatment of metabolic syndrome.

Suggested reading:

• Grundy SM. Definition of Metabolic Syndrome (Report of the National Heart, Lung, and Blood Institute/ American Heart Association Conference on Scientific Issues Related to Definition). Circulation. 2004;109:433-438.
• Metabolic Syndrome: New Opportunities in Diagnostics and Therapeutics (D&MD Reports; http://www.drugandmarket.com/9135)

Table 1

Examples of drugs with potential application in the treatment of metabolic syndrome*

*All drugs listed are approved in the U.S. with the exception of Acomplia™ (rimonabant).

Source: D&MD

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