Repatha (Evolocumab) Drug Classification
Repatha (evolocumab) is a PCSK9 inhibitor, specifically a fully human monoclonal antibody that targets and inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9) protein. 1, 2
Mechanism of Action
Evolocumab works through a distinct mechanism:
- It binds to circulating PCSK9 in the bloodstream, preventing PCSK9 from binding to LDL receptors on liver cells 1
- By blocking PCSK9, evolocumab prevents the degradation of LDL receptors and allows them to be recycled back to the cell surface 2
- This increases the number of available LDL receptors on liver cells, enhancing LDL cholesterol clearance from the bloodstream 1, 2
Clinical Efficacy
PCSK9 inhibitors like evolocumab demonstrate remarkable lipid-lowering effects:
- Reduces LDL cholesterol by 50-65% when added to statin therapy 3, 4
- Lowers lipoprotein(a) by up to 25% 3
- Increases HDL cholesterol by approximately 4.5-6.8% 3
- Also reduces total cholesterol and apolipoprotein B levels 3, 2
Administration
Repatha is administered as:
- 140 mg subcutaneous injection every 2 weeks, or
- 420 mg subcutaneous injection once monthly 2
Clinical Applications
Evolocumab is FDA-approved for:
- Heterozygous familial hypercholesterolemia (HeFH) 3, 2
- Homozygous familial hypercholesterolemia (HoFH) 3, 2
- Established atherosclerotic cardiovascular disease (ASCVD) requiring additional LDL-C reduction 3, 5
- Patients with LDL-C ≥100 mg/dL despite maximally tolerated statin and ezetimibe therapy 3
- Patients at very high cardiovascular risk with LDL-C ≥70 mg/dL despite optimal therapy 3
Clinical Outcomes
The FOURIER trial demonstrated that evolocumab:
- Reduced major cardiovascular events by 15% over 2.2 years in patients with ASCVD 3
- Reduced the composite of cardiovascular death, MI, or stroke by 20% 3
- Maintained an excellent safety profile, even in patients achieving very low LDL-C levels 5