Looking into the Future

The American pharmaceutical industry spent more than $30 billion in 2001 researching and developing new drugs. Not surprisingly, companies tend to focus much of their research in areas that promise the biggest sales potential, such as diabetes, heart disease, and cancer. And with an estimated 36 million Americans walking around with cholesterol levels high enough to qualify them for medication, along with the success of the statin drugs, it’s not surprising drug companies are anxious to bring new cholesterol medications to market. Here, then, is a snapshot of what’s in the works:

CETP inhibitors. During the 1990s researchers discovered a protein called cholesterol ester transfer protein (CETP), responsible for the transfer of fats between lipoproteins. People with high blood levels of CETP generally have low levels of HDL. The finding sent pharmaceutical scientists scrambling to find a drug that would reduce or inhibit the production of CETP. Although several such drugs are in the works, the one closest to market is Pfizer Inc.’s CP-529,414. Although the drug is too experimental to have a real name, its benefits are already being bandied about in medical meetings. In trials the drug raised HDL levels a whopping 55 percent—about10 times more than typically seen with statins. It also lowered LDL up to 20 percent. Overall, when used in combination with Pfizer’s statin, Lipitor, company officials estimate it could lower LDL 70 to 80 percent, while raising HDL 55 percent. It is likely years away from FDA approval, however.

Cholesterol vaccine. Avant Irmunotherapeutics Inc. is working to develop a cholesterol vaccine that controls the CETP protein, thus increasing HDL levels and helping prevent heart disease. As envisioned, the vaccine would need to be given only once every six months. Additionally, because the peptide used in the drug is simple and cheap to manufacture, Avant expects the cost of the vaccine would be considerably less than that of statins.

ACAT inhibitors. This class of drug works to inhibit an enzyme, acyl coenzyme A; cholesterol acyltransferase (ACAT), that helps foam cells—a major component of and contributor to plaque—develop. In studies these drugs appear to clear up existing plaque even as they prevent the formation of additional plaque. Pfizer’s avasimibe was in late-stage clinical trials in early 2003, while Eli Lilly and Co.’s eflucimibe had just begun studies in humans. These drugs aren’t expected to hit the market before mid- to late in the decade.

New statins. Two new statins under development could be approved as early as 2003 or 2004 in the United States: 

• Crestor (rosuvastatin). This statin, which will be marketed by AstraZeneca Pharmaceuticals, was closest to approval as of this writing. It’s called a “super statin” because of its impressive results in lowering LDL and total cholesterol levels. In one study Crestor reduced LDL 40 to 58 percent, beating out Lipitor, Zocor, and Pravachol. The most common side effects are nausea, diarrhea, dry mouth, and abdominal pain, although symptoms rarely resulted in patients quitting the drug. Crestor also increased HDL levels up to 14 percent, and it reduced apo(b)/A-1 levels, a CHD risk predictor.
• Pitavastatin. Developed by the Japanese drugmaker Sankyo Co., this drug lowered LDL levels nearly 38 percent after 12 weeks compared to Pravachol, which lowered LDL levels only 18 percent. The study found that 75 percent of patients treated with the drug reached their LDL goal, compared to just 36 percent of those taking Pravachol. Pitavastatin also reduced triglyceride levels but had no effect on HDL levels. Pharmaceutical company Novartis AG may market the drug in the United States if and when it receives FDA approval.

Ileal bile acid transport (IBAT) inhibitors. This class of drug prompts the liver to convert cholesterol into bile acids, thus reducing cholesterol levels in the liver. When this happens, the liver sends out for more cholesterol, taking it from the bloodstream and reducing blood cholesterol levels. The primary side effect is diarrhea. These drugs are several years away from FDA approval.

Dual peroxisome proliferator-activated receptor (PPAR) agonists. These drugs reduce triglycerides, raise HDL, and improve insulin resistance, making them particularly well suited for people with diabetes or metabolic syndrome. The drugs are years away from the market, however.