What is Repatha (evolocumab) used for?

Repatha (Evolocumab) Uses and Indications

Repatha (evolocumab) is primarily used to reduce the risk of major cardiovascular events in adults with established cardiovascular disease and to lower LDL cholesterol in patients with various forms of hyperlipidemia when other treatments are insufficient. 1

FDA-Approved Indications

Repatha is indicated for:

1. Cardiovascular Risk Reduction

   • To reduce the risk of major adverse cardiovascular events (CV death, myocardial infarction, stroke, unstable angina requiring hospitalization, or coronary revascularization) in adults with established cardiovascular disease 1

2. Primary Hyperlipidemia

   • As an adjunct to diet, alone or in combination with other LDL-C-lowering therapies, in adults with primary hyperlipidemia, including heterozygous familial hypercholesterolemia (HeFH), to reduce LDL-C 2, 1

3. Pediatric Heterozygous Familial Hypercholesterolemia

   • As an adjunct to diet and other LDL-C-lowering therapies in pediatric patients aged 10 years and older with HeFH, to reduce LDL-C 1

4. Homozygous Familial Hypercholesterolemia

   • As an adjunct to other LDL-C-lowering therapies in adults and pediatric patients aged 10 years and older with homozygous familial hypercholesterolemia (HoFH), to reduce LDL-C 2, 1

Mechanism of Action

Repatha is a human monoclonal antibody that targets PCSK9 (proprotein convertase subtilisin/kexin type 9). It works by:

• Binding to PCSK9 in the bloodstream
• Increasing the number of LDL receptors available on liver cells
• Enhancing the liver's ability to remove LDL cholesterol from the blood 2

Dosing and Administration

Repatha is administered subcutaneously in the thigh, abdomen, or upper arm in two possible dosing regimens:

• Standard dosing: 140 mg every 2 weeks
• Alternative dosing: 420 mg once monthly 2

For patients with HoFH:

• Initial dose: 420 mg once monthly
• If additional LDL-C reduction is needed after 12 weeks, may increase to 420 mg every 2 weeks 2

Clinical Efficacy

• Reduces LDL-C by 50-65% when added to maximally tolerated statin therapy 2
• Can achieve mean LDL-C levels of approximately 35 mg/dL, with many patients reaching levels below 25 mg/dL 2
• In the FOURIER trial, evolocumab reduced:
  • LDL-C by 59% (from median 92 to 30 mg/dL)
  • Composite outcome of cardiovascular death, MI, stroke, hospitalization for angina, or revascularization by 15%
  • Combined endpoint of cardiovascular death, MI, or stroke by 20% 2

Safety Profile

Repatha is generally well tolerated with:

• Injection site reactions (relatively infrequent and mild)
• Potential hypersensitivity reactions (rare)
• No significant increase in muscle-related adverse events compared to ezetimibe in statin-intolerant patients 2

Important Considerations

• Latex sensitivity: Some prefilled SureClick autoinjectors and syringes contain dry natural rubber (a derivative of latex) in the needle cover, which may cause allergic reactions in latex-sensitive individuals 1
• Pregnancy: Limited data available; patients who become pregnant while taking Repatha should report to the manufacturer's pregnancy registry 1
• Cost and access: May require prior authorization from insurance providers 2

Repatha represents an important therapeutic option for patients who cannot achieve adequate LDL-C reduction with statins alone or who cannot tolerate statins, particularly those at high cardiovascular risk.