Getting It Approved

One example is Pfizer's new product Caduet (amlodipine and atorvastatin), which is designed to help people lower their blood pressure and cholesterol by taking just one pill daily. This new tablet is the first to combine medicines that address two different disorders simultaneously. The company estimates that 30 million Americans suffer from both high cholesterol and elevated blood pressure—the two leading risk factors for heart disease. Analysts forecast that Pfizer will generate $200 million in Caduet sales this year and $400 million in 2005.

Another example is Vytorin, a cardiovascular therapy comprising Schering-Plough's Zetia (ezetimibe) and Merck's Zocor (simvastatin) that reduces cholesterol in different ways. Ezetimibe is a cholesterol-absorption inhibitor, whereas simvastatin decreases endogenous liver production of cholesterol by inhibiting HMG-CoA reductase. The combination of these two different mechanisms could achieve additive or synergistic cholesterol-lowering effects.

Indeed, the financial reward for pharma can be lucrative because the new combinations often come with fresh patents that protect the medicines from similar generic combinations for years after the individual ingredients have lost their legal protection.

Some new drugs may become available only as part of a combination pill. A Pfizer mixture in development combines Lipitor (atorvastatin), which works primarily to reduce bad cholesterol (low-density lipoprotein), with an experimental drug, torcetrapib, which raises good cholesterol (high-density lipoprotein). This combination, which has not yet been named, could be marketed in two or three years, and torcetrapib will be sold only in combination with atorvastatin. Lehman Brothers estimates global peak sales will be $1.5 billion.

Filling the Gap As pressures mount to build up their pipelines, most major pharma companies are mixing current or past blockbusters to help fill the product void. Because of a high percentage of failures during trials, the amount companies must spend to bring a single drug to market in the United States has grown to approximately $1.7 billion, according to Bain & Co.

Bain points out that pharma companies are earning only a 5 percent return on their investment in finding new drugs, below levels typically demanded by equities investors. The Bain report also notes that licensing products from other companies, which was a profitable strategy until recently, now brings only a 6 percent return on investment. The trend has been for large pharma companies to design strategies around blockbuster products for widespread ailments such as heartburn, high cholesterol, and depression. But many of these products are losing patent protection and are being replaced by lower priced generics.

Although pharma companies will not likely abandon the blockbuster model, it is inevitable that they will aggressively deal with increased pressure on R&D, aging facilities, and expensive work forces by identifying alternative strategies to support their growth. The focus on combination products, although not a strategy that will single-handedly solve these challenges, can ameliorate them by effectively blunting competition from generics, thus increasing the market presence of mature brands as well as enhancing patient compliance.

Winning Over Doctors Despite the move toward combo products, some physicians prefer to prescribe separate drugs to customize patients' medical regimens. These doctors often avoid prescribing combination drugs because they are offered in a limited number of dosages, which makes it difficult to tailor drug regimens or solve patients' problems with a single pill. Specifically, some physicians are concerned that they may not be able to isolate the cause if a patient experiences side effects from a combo product.