Basic Information About Repatha (Evolocumab)

Injectable medication
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 Repatha (evolocumab) is a medication that is used to lower LDL cholesterol levels and is indicated for individuals who have been diagnosed with atherosclerotic cardiovascular disease,  homozygous (HoFH) or heterozygous (HeFH) familial hypercholesterolemia and still have elevated LDL cholesterol levels despite already taking a statin or other cholesterol-lowering treatment. Repatha is classified as a proprotein convertase subtilisin kexin 9 (PCSK9) inhibitor and is the second cholesterol-lowering medication in this class.

Repatha was approved for use by the Food and Drug Administration (FDA) in August 2015.

The safety and effectiveness of Repatha has been evaluated in several different studies, including:

  • RUTHERFORD 2 – This clinical trial examined the use of Repatha in individuals diagnosed with HeFH taking a statin - with or without additional cholesterol-lowering medications – versus a placebo.
  • TESLA Part B – This clinical trial examined the use of Repatha in participants diagnosed with HoFH taking Zetia or statin therapy compared to a placebo.
  • DESCARTES – This clinical trial included anyone who had an LDL cholesterol level that was 75 mg/dL or greater and were following a healthy diet alone, consuming a healthy diet and taking a statin drug, taking a statin drug alone, or taking a statin drug with Zetia. Repatha was compared to a placebo.
  • OSLER 1 and 2 – This clinical trial examined safety and effectiveness of Repatha in individuals from other Repatha trials diagnosed with HoFH, HeFH or elevated LDL levels - regardless of whether or not they were taking Repatha in their previous study. Participants took Repatha with other cholesterol-lowering drugs or took standard therapy alone.

    Most studies revealed that LDL cholesterol levels were lowered by up to about 30 to 60% compared to placebo. These studies examined Repatha safety and effectiveness for a duration anywhere between 12 weeks and 1 year. One study suggested that individuals taking Repatha for one year were at lower risk of experiencing a cardiovascular event compared to those receiving other therapies.

    However, this is still currently under investigation.

     

    How Does Repatha Work?

    Repatha is a type of human monoclonal antibody directed against proprotein convertase subtilisin kexin 9 (PCSK9) proteins. PCSK9 proteins are responsible for binding to LDL receptors and promoting their breakdown in the liver. LDL receptors function by removing LDL cholesterol circulating in the blood. If LDL receptors are broken down, LDL cannot be properly removed from the body. This will result in LDL levels building up in the blood.

    When Repatha binds to PCSK9, it prevents the protein from interacting with LDL receptors and causing them to be degraded. This will allow LDL receptors to continue to function by removing LDL from the body – resulting in lowered LDL cholesterol levels.

     

    How Should You Take Repatha?

    Repatha should be taken in conjunction with a cholesterol-lowering diet. Recommended doses of Repatha depend upon your disease state. If you have HeFH, you should administer 140 mg of Repatha underneath the skin (subcutaneously) every two weeks as directed by your healthcare provider.

    One already prepared syringe contains 140 mg. You can also inject 420 mg once a month subcutaneously.

    If you have HoFH, the recommended dose is 420 mg subcutaneously every month. To do this, three syringes of Repatha should be injected under the skin within a 30 minute period.

    Your healthcare provider will show you how to use the Repatha syringes and direct you on how to administer the drug. The medication can be given in the abdomen, upper arm, and or thigh and the injection sites should be rotated regularly.

     

    What Side Effects Should I Expect?

    The most common side effects experienced by individuals taking Repatha included:

    • Upper respiratory tract infections
    • Coughing
    • Injection site reactions (such as redness or swelling at the injection site)
    • Dizziness
    • Influenza
    • Gastroenteritis
    • Nasopharyngitis

    Allergic reactions may also occur when taking this medication. These can range from developing an itchy rash to anaphylaxis. If a serious allergic reaction occurs, you should seek emergency attention immediately and notify your healthcare provider.

     

    Who Should Not Take Repatha?

    If you have had a severe allergic reaction to Repatha in the past, you should not take this medication. The safety and effectiveness of Repatha has not been extensively studied in some medical conditions and populations, including:

    • Women who are pregnant or breastfeeding
    • Severe liver disease
    • Severe kidney disease
    • Children with HoFH under 13 years of age
    • Children with HeFH

    Your healthcare provider will evaluate the benefits and risks of prescribing Repatha to you if you fit in one of the above categories. Although there are no human pregnancy studies available, animal studies conducted so far have noted no effects on pregnancy or fetal development in pregnant animals administered Repatha.

     

    Can Repatha Interact with Any Medications I Am Taking?

    There does not appear to be significant drug interactions associated with Repatha in studies conducted so far. However, you should notify your healthcare provider of any medications you are taking with your Repatha – including any prescribed, over-the-counter, and herbal medications. This will help them to track any possible interactions that may occur.

     

    Bottom Line

    Repatha is the second PCSK9 inhibitor approved in the US. Although it has been approved for use in people who have atherosclerotic cardiovascular disease, HeFH, or HoFH in need of additional treatment to lower LDL along with other cholesterol-lowering therapies, it is not currently recommended in other situations of LDL elevation. There are currently no studies published directly comparing Repatha with Praluent, the other cholesterol-lowering medication in this class. However, there are studies currently underway that further investigate long-term effectiveness, safety, and disease outcomes in individuals taking Repatha. 

     

    Sources:

    Repatha® (evolocumab) Package Insert. Amgen Inc. September 2015.

    Sabatine MS, Giugliano RP, Wiviott SD et al. Efficacy and safety of evolocumab in reducing lipids and cardiovascular events. New Eng J Med 2015;372:1500-1509.

    Blom DJ, Hala T, Bolognese M, et al. A 52 week placebo-controlled trial of evolocumab in hyperlipidemia. New Eng J Med 2014;370:1809-1819.

    Raal FJ, Stein EA, Dufour R et al. PCSK9 inhibition with evolocumab (AMG 145) in heterozygous familial hypercholesterolaemia (RUTHERFORD-2): a randomised, double-blind, placebo-controlled trial. Lancet 2015;385:331-340.

    Raal FJ, Hanapour N, Blom DJ et al. Inhibition of PCSK9 with evolocumab in homozygous familial hypercholesterolaemia (TESLA Part B): a randomised, double-blind, placebo-controlled trial. Lancet 2015;385:341-350.

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