The FDA approved the new injectable drug Praluent (alirocumab) on July 24, 2015 for the treatment of heterozygous familial hypercholesterolemia (HeFH) or for patients with clinical atherosclerotic cardiovascular disease. HeFH causes abnormally high levels of low-density lipoprotein (LDL) cholesterol. People with HeFH often have trouble lowering their cholesterol with diet, exercise and statin drug therapy. Atherosclerosis is caused by high levels of LDL (bad) cholesterol in the blood. Sustained high levels of LDL can narrow and form hard plaques in the arteries. These plaques may eventually detach and cause a heart attack or stroke. Increased LDL cholesterol is linked to heart disease and causes about 610,000 deaths in the United States (one in every four deaths) each year.
High levels of LDL cholesterol is predominantly treated with a class of drugs called statins. Statins reduce cholesterol levels by preventing the formation of cholesterol in the liver. They are effective at reducing the incidence of heart attack, stroke and other cholesterol-related events. However, most people with HeFH cannot achieve adequate cholesterol reduction with statins alone and many people cannot tolerate maximum doses of statins.
Praluent is used in combination with diet and maximum tolerated statin doses, leading to decreases in cholesterol that were not possible with statins alone. This is an exciting new drug because it adds to the options for reducing cholesterol in people who require further cholesterol reduction while taking maximum tolerated statin doses. Praluent is the first drug in a brand new class of drugs known as proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors. Unlike statins, which reduce the amount of LDL produced, Praluent is an antibody that targets and blocks the action of PCSK9. PCSK9 is a protein that causes destruction of receptors that remove cholesterol from the blood. Praluent allows more receptors to be available to remove LDL cholesterol from the blood by blocking the action of PCSK9. The net effect of Praluent is a decrease in LDL cholesterol levels.
The evidence for Praluent’s efficacy in reducing LDL was obtained from five studies that included 3,499 patients with HeFH (36%) or clinical atherosclerotic cardiovascular disease (54%). All patients were receiving maximally tolerated doses of statins. All trials were at least 52 weeks in duration and the main endpoint was average change in LDL cholesterol measured at week 24. Patients were treated with 75 mg or 150 mg of Praluent every 2 weeks or placebo. Praluent’s average reduction in LDL ranged from 36 to 59% compared to placebo. The effect of Praluent on cardiovascular morbidity and mortality has not yet been determined. Researchers are hopeful that Praluent will provide additional risk reduction because there is strong evidence that reducing cholesterol reduces the risk of having a heart attack or stroke. A trial evaluating the effect of adding Praluent to statins on reducing cardiovascular risk is ongoing.
Praluent is only available by injection. Common side effects of Praluent injections are itching, swelling, pain or bruising at the site of injection, and cold and flu-like symptoms. Serious allergic reactions, diarrhea, muscle pain, muscle spasms, and urinary tract infections may also occur.
Praluent is available as a 1 milliliter (mL) single-dose prefilled pen or syringe containing 75 or 100 mg. It is injected once every two weeks. Wholesale Acquisition Cost (WAC) is $40 per day for both the 75 mg and 150 mg doses. Praluent is made by Sanofi and Regeneron Pharmaceuticals, Inc. Other pharmaceutical companies are currently working on PCSK9 inhibitors including Pfizer, Alnylam and Esperion.
FDA News Release - FDA.gov
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