The FDA has approved Repatha (evolocumab) injection, a human monoclonal antibody that works to decrease low-density lipoprotein cholesterol.
The FDA has approved Repatha (evolocumab) injection, a human monoclonal antibody that works to decrease low-density lipoprotein cholesterol (LDL-C). It is indicated as an adjunct to diet and maximally tolerated statin therapy for adults with heterozygous familial hypercholesterolemia (HeFH) or clinical atherosclerotic cardiovascular disease (CVD) who require additional lowering of LDL-C, as well as an adjunct to diet and other LDL-C lowering agents in adults with homozygous familial hypercholesterolemia (HoFH) who require additional lowering of LDL-C.
The approval carries the limitation that the effect of Repatha on cardiovascular morbidity and mortality has not been determined.1-3 A trial is currently underway to evaluate if treatment with Repatha in addition to statin therapy will reduce the risk of recurrent cardiovascular events.2,3 Heart disease is the leading cause of death for both men and women in the United States. Repatha is the second drug in its class to receive FDA approval.3
Pharmacology and Pharmacokinetics
Repatha is a proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitor antibody. By binding to PCSK9 and inhibiting circulating PCSK9 from binding to the LDL receptor (LDLR), PCSK9-mediated LDLR degradation is prevented and LDLR is recycled back to the surface of the liver cell. This increases the number of LDLRs available to clear LDL from the blood, resulting in lower LDL-C levels.
The pharmacokinetics of Repatha were not affected by age, gender, race, or creatinine clearance. Dose adjustment is not required in patients with mild to moderate renal or hepatic impairment.1
Dosage and Administration
Repatha should only be given by subcutaneous injection in the abdomen, thigh, or upper arm. Patients with primary hyperlipidemia with established clinical atherosclerotic CVD or HeFH should receive 140 mg subcutaneously every 2 weeks or 420 mg subcutaneously once monthly. Patients with HoFH should receive 420 mg subcutaneously once monthly.
Repatha is supplied as a 140 mg/ mL-prefilled single-use syringe or SureClick autoinjector. To give the 420-mg dose, three 140-mg injections should be administered consecutively within 30 minutes.1
A total of 4 trials evaluated the use of Repatha in adult patients. Two trials evaluated the role of Repatha in primary hyperlipidemia in patients with clinical atherosclerotic CVD. Study 1 was a multicenter, double-blind, randomized controlled trial of 296 patients who received Repatha 140 mg every 2 weeks, Repatha 420 mg every month, or placebo as add-on treatment to their current statin therapy (atorvastatin 80 mg daily, simvastatin 40 mg daily, or rosuvastatin 40 mg daily). At 12 weeks, the mean reduction from baseline LDL-C between Repatha and placebo was 71% in the Repatha 140-mg group and 63% in the Repatha 420-mg group.
Study 2 was a 52-week, multicenter, double-blind, randomized, placebo-controlled trial of 139 patients. After stabilization on atorvastatin 80 mg daily with or without ezetimibe 10 mg daily, patients were randomized to receive either placebo or Repatha 420 mg once monthly. At the study’s end, the mean reduction from baseline LDL-C between placebo and Repatha was 54%.
Study 3 evaluated Repatha in patients with HeFH in a multicenter, double-blind, randomized, placebocontrolled trial of 329 patients on statins with or without other lipid-lowering medications. Patients received Repatha 140 mg every 2 weeks, Repatha 420 mg every month, or placebo. At 12 weeks, the mean reduction from baseline LDL-C between Repatha and placebo was 61% for the 140-mg group and 60% for the 420-mg group.
Study 4 evaluated Repatha in patients with HoFH in a multicenter, double-blind, randomized, placebocontrolled trial of 49 patients who received either Repatha 420 mg monthly or placebo in addition to other lipid-lowering medications. At 12 weeks, the mean reduction from baseline LDL-C between Repatha and placebo was 31%.1
Contraindications, Warnings, Precautions
Repatha is contraindicated in patients with a history of a serious hypersensitivity reaction to the medication. If rash and urticaria occur, discontinue treatment with Repatha, treat according to the standard of care, and monitor until signs and symptoms resolve. In clinical trials, the most common adverse reactions (>5% of patients) were nasopharyngitis, upper respiratory tract infection, influenza, back pain, and injection site reactions.1
Dr. Holmberg earned her PharmD from the University of Connecticut and completed an ambulatory care residency at the Phoenix VA Healthcare System. Her practice has also included pediatrics and inpatient mental health. She resides in Phoenix, Arizona.
- Repatha [package insert]. Thousand Oaks, CA: Amgen; 2015.
- FDA approves Amgen's new cholesterol-lowering medication Repatha (evolocumab) [news release]. Thousand Oaks, CA: Amgen; August 27, 2015. www.amgen.com/media/media_pr_detail.jsp?year=2015&releaseID=2082837. Accessed September 29, 2015.
- FDA approves Repatha to treat certain patients with high cholesterol [news release]. Silver Spring, MD: FDA; August 27, 2015. www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm460082.htm. Accessed September 29, 2015.