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PCSK9 drugs can reduce blood levels of cholesterol, which builds up in arteries (above), but only now have they been shown to prevent heart attacks and strokes.

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Pricey new cholesterol drug scrapes by in heart risk study

A year and a half after its feted approval, a new cholesterol drug has passed a key test. There was no question that Repatha, an antibody drug developed by Amgen, could provide stunning drops in cholesterol for people who have already maxed out the benefits of decades-old statin drugs. But the clinical trials supporting its approval did not take the next step to show whether the therapy, known as a PCSK9 inhibitor, could actually improve or extend the lives of people taking it.

Now, those results are in. Repatha showed a measurable—if modest—benefit in reducing cardiovascular events such as heart attacks and stroke. “The open question was, ‘Does this way of lowering [cholesterol] reduce risk of coronary heart disease,’” says Sekar Kathiresan, a cardiologist at the Massachusetts General Hospital in Boston and the Broad Institute in Cambridge, Massachusetts, who was not involved in the study. “The answer to that is a firm ‘yes.’ And that’s exciting.”

The drug reduces cholesterol—specifically, low-density lipoprotein (LDL) cholesterol that can build up in artery walls—by blocking an enzyme known as PCSK9, which would otherwise inhibit liver receptors that clear LDL cholesterol from the body. In clinical trials, both Repatha and its competitor, a drug called Praluent developed by Sanofi and Regeneron, reduced LDL cholesterol by about 60% in patients already taking statins. That was good enough for the U.S. Food and Drug Administration (FDA), which approved both drugs in 2015. (The two companies are locked in a patent dispute, in which Amgen is attempting to block Praluent from the market.)

Researchers knew there was a general relationship between cholesterol levels and cardiovascular disease risk, but “there was sort of a question of whether, when you get to very low [cholesterol] levels, that relationship would fall off,” says William Hiatt, a physician specializing in vascular medicine at the University of Colorado in Denver and a member of an FDA advisory committee that reviewed the drugs.

Both groups launched trials to answer that question; Amgen is the first to release its findings. The company collaborated with several institutions, including Brigham and Women’s Hospital in Boston and Imperial College London, to enroll about 27,000 patients with a history of cardiovascular disease who were already taking statins. The researchers randomized patients to receive either injections of Repatha or placebo, and followed them for 2 years to track several cardiovascular events: heart attack, stroke, death, hospitalization for blocked blood flow to the heart, and stent or bypass surgery. After 2 years, 9.8% of patients in the treatment group had at least one such event, versus 11.3% in the placebo group, the team revealed today in The New England Journal of Medicine and at a meeting of the American College of Cardiology in Washington, D.C.

In other words, a physician would need to treat about 150 patients with Repatha in a year to prevent one of these bad events, Hiatt explains. “The benefit here is meaningful and substantial,” he says, “although not overwhelming.” Given that many patients at risk of a heart attack or stroke have little else to try, he says, this is “absolutely an advance in cardiovascular medicine.”

The question insurance companies are grappling with is whether that benefit justifies the list price of nearly $15,000 a year. “It’s an expensive medicine for a common disease, says Kathiresan, “and my sense is that the price will have to come down.”

Still, the result is gratifying for researchers hoping genomic studies will serve up new drugs. The drug’s mechanism of action was discovered by studying people with mutations to the gene for PCSK9 that allowed them to maintain exceptionally low cholesterol levels. “The therapies basically exactly mirror the human genetics,” Kathiresan says. “This is potentially a road map for medicines development at large.”