A new not-yet-published study presented at the American Heart Association’s Scientific Sessions (November 16 to 18, 2019) in Philadelphia has found that an experimental new medication called inclisiran may significantly lower cholesterol levels in individuals who have atherosclerotic cardiovascular disease and were already taking maximally tolerated oral statins but had persistently high bad cholesterol (low-density lipoproteins, or LDL). Based on trial results involving 1,561 participants (average age 66) with atherosclerotic cardiovascular disease, inclisiran was shown to reduce LDL by up to 58 percent over the course of 18 months compared with those taking a placebo, according to an announcement from The Medicine Company, developers of the drug. “There’s such a high-risk population on statins who can get an additional benefit [from inclisiran],” says R. Scott Wright, MD, principal investigator and professor of medicine with the division of structural heart disease in the department of cardiovascular medicine at the Mayo Clinic in Rochester, Minnesota. “If inclisiran is approved, it’s another option to take on top of a statin, but it’s only twice a year.”
Appeal of a Drug Taken Every Six Months
Inclisiran joins a type of drug called PCSK9 inhibitors. The PCSK9 gene makes a protein that helps regulate the amount of cholesterol in the bloodstream. Inclisiran lowers cholesterol by preventing production of PCSK9 in the liver. Other PCSK9 drugs currently on the market include Repatha (evolocumab) and Praluent (alirocumab) — both have been shown to significantly lower LDL, according to Harvard Health Publishing. They work by blocking PCSK9 after it has been produced, while inclisiran blocks the genetic expression of the protein. Although inclisiran (like Repatha and Praluent) is an injected medication, one of its attractions for some patients is that it is designed to be given only two times a year. Statins require a daily pill, and Repatha and Praluent must be taken at least once a month. In this trial, individuals received inclisiran on day one and day 90, and then every six months thereafter. Dr. Wright points out that a small percentage of study participants who were statin-intolerant and not on any therapy also lowered their LDL. “Inclisiran can be given without statins and works effectively whether you’ve taking a statin or not,” he says. “I’ve had a number of patients say to me, ‘Can you replace my pills with something I can take once or twice a year as an injection?’ I think there’s a strong case to be made for a trial comparing inclisiran with statins without background statin therapy.” At this time, however, The Medicines Company has no plans to move forward with such a primary prevention trial.
Concerns and Opportunities Ahead
Sarah Samaan, MD, a cardiologist with Baylor Scott & White Legacy Heart Center in Plano, Texas, who was not involved in the study, stresses that the drug is still in the experimental stages. “More testing is needed before it is ready for prime time,” she says. “While it clearly has a great effect at lowering LDL cholesterol, we need to be certain that that reduction translates into a lower risk for heart attack and stroke.” Dr. Samaan also warns that the medication will be an option only for those who fail statin therapy or are unable to take statins due to side effects. The medication is also likely to be far more expensive than a statin. estimates that statins can cost as little as $36 a month. Repatha — a PCSK9 inhibitor like inclisiran — lists its price as $450 a month. Research on inclisiran is ongoing to prove its efficacy and safety, although the medication has posed no safety issues so far, according to Wright. No treatment has been required due to liver or kidney abnormalities. Wright anticipates the drug to be submitted to the U.S. Food and Drug Administration (FDA) for approval by the end of this year, which means that it would not be on the market until some time in 2021. For now, Wright extends this advice to patients taking statins: “Take your medicines but realize the field is exploding with new opportunities. Talk to your healthcare provider because new options will be coming along.”
