New drugs to lower cholesterol on the horizon

By Deborah Kotz, Globe Staff

Since hitting the market a quarter-century ago, cholesterol-lowering statin drugs have become one of the most popularly prescribed medications. Giant trials have shown that the medications not only effectively lower “bad” LDL cholesterol in those with elevated levels but more importantly, lower the risk of having a heart attack or dying from heart disease or a stroke.

Where researchers once worried that statins might increase the risk of cancer, they’ve now found that statin users have a 15 percent lower risk of dying from cancer as well as other causes. In a study published Wednesday in the New England Journal of Medicine, Danish researchers examined medical records of all cancer patients in their country diagnosed between 1995 and 2007 and found that those who took statins had a smaller likelihood of dying over a 2.5 year period than those who didn’t.

But as potent as statins are to lower high cholesterol and reduce inflammation associated with heart disease and cancer, they don’t work for everyone. About 30 to 50 percent of patients with high cholesterol can’t get their LDL levels down to a healthful level with statins, according to Dr. Robert Giugliano, a cardiologist at Brigham and Women’s Hospital.

Some patients can’t tolerate them because they have liver side effects or severe muscle aches, while others find that their cholesterol levels drop on the maximum dose of the most potent statin but not enough to get them to the recommended level needed to lower their heart risk.

Giugliano and others have been conducting preliminary trials with a new class of experimental drugs that could be taken along with statins or on their own to lower cholesterol levels. Several of the early results indicate that the medications -- injections given weekly, biweekly, or monthly -- have no (as of yet) significant side effects and work well to lower LDL levels.

Amgen, Pfizer, and Sanofi/Regeneron have all developed compounds -- in a class of drugs called monoclonal antibodies -- that bind to a protein called PCSK9 circulating in the blood. which normally attaches to LDL receptors on liver cells and prevents these receptors from removing LDL cholesterol from the blood. When the drugs bind to PCSK9, the protein can’t attach to the LDL receptors, freeing up liver cells to soak up LDL cholesterol and effectively remove excess amounts from circulating in the bloodstream.

In a manufacturer-sponsored trial published online this week in the journal Lancet, Giugliano and his colleagues administered various doses of Amgen’s monoclonal antibody injections or placebo injections to 631 patients with high cholesterol levels who were already taking statins. Those who had the injections every two weeks for nearly three months experienced a 42 to 66 percent bigger reduction in LDL cholesterol levels, compared with patients who got the placebo, with the greatest effect occurring with the highest dose; those who had the injections monthly had a 42 to 50 percent greater drop in their LDL levels compared with the placebo.

Other researchers found similar results when using the Amgen injections in those who weren’t taking any statins. Sanofi/Regeneron and Pfizer have also had similar success with their PCSK9-targeting injections in early clinical trials that were presented at the American Heart Association’s annual meeting this week in Los Angeles.

What’s needed now, Giugliano said, are much larger studies involving thousands of patients who are given these injections for at least five years to study their long term safety and efficacy. Sanofi and Regeneron Pharmaceuticals announced this week that they’re beginning a Phase 3 trial involving 18,000 heart disease patients, which is necessary to receive approval from the US Food and Drug Administration. Amgen will start its own Phase 3 trial next year.

The manufacturers haven’t yet determined the cost of each injection, which even if administered on a monthly basis, will no doubt be pricier than daily statin pills--most of which are now available as generics.

“These new monoclonal antibodies present a huge opportunity for many new patients to reach their cholesterol goals,” Giugliano added, “but first we have to see if there are any real safety problems.”

Deborah Kotz can be reached at dkotz@globe.com. Follow her on Twitter @debkotz2.