What is Repatha (Evolocumab) pre-filled pen 140mg/ml used for in treating high cholesterol?

Repatha Pre-Filled Pen 140mg/mL

Repatha (evolocumab) pre-filled pen 140mg/mL is a subcutaneous PCSK9 inhibitor monoclonal antibody used to dramatically lower LDL cholesterol by approximately 60% in patients with atherosclerotic cardiovascular disease or familial hypercholesterolemia who require additional LDL-C lowering beyond maximally tolerated statin therapy. 1

Mechanism of Action

• Evolocumab is a fully human monoclonal IgG2 antibody that binds to and inhibits PCSK9 (proprotein convertase subtilisin kexin type 9), preventing PCSK9 from binding to LDL receptors on hepatocytes 1
• By blocking PCSK9, evolocumab increases the number of LDL receptors available on liver cells to clear LDL cholesterol from the blood, resulting in substantial LDL-C reduction 1
• Maximum suppression of circulating unbound PCSK9 occurs within 4 hours of administration, with maximum LDL-C reduction achieved by 2 weeks after a single 140mg dose 1

FDA-Approved Indications

• Atherosclerotic cardiovascular disease (ASCVD): As adjunct to maximally tolerated statin therapy in adults with established ASCVD who require additional LDL-C lowering 1
• Heterozygous familial hypercholesterolemia (HeFH): In adults and pediatric patients aged 10 years and older as adjunct to diet and other LDL-C-lowering therapies 1
• Homozygous familial hypercholesterolemia (HoFH): In adults and pediatric patients aged 10 years and older as adjunct to other LDL-C-lowering therapies 1

Dosing and Administration

• The 140mg pre-filled pen is administered subcutaneously every 2 weeks, or alternatively 420mg can be given once monthly based on patient preference 2, 1
• Each 1 mL pre-filled pen contains 140mg evolocumab in a sterile, preservative-free, clear to opalescent solution 1
• The medication exhibits an effective half-life of 11 to 17 days with steady-state concentrations approached by 12 weeks of dosing 1

Clinical Efficacy

• In the landmark FOURIER trial of 27,564 patients with ASCVD on maximally tolerated statin therapy, evolocumab reduced LDL cholesterol by 59% from a median of 92 mg/dL to 30 mg/dL 2, 3
• Evolocumab significantly reduced the composite primary endpoint of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization (9.8% vs 11.3%; hazard ratio 0.85; 95% CI 0.79-0.92; P<0.001) 3
• The key secondary endpoint of cardiovascular death, myocardial infarction, or stroke was reduced from 7.4% to 5.9% (hazard ratio 0.80; 95% CI 0.73-0.88; P<0.001) 3
• Across 12-week phase III trials, evolocumab demonstrated LDL-C reductions of 54.8% to 76.3% compared to placebo and 36.9% to 47.2% compared to ezetimibe 4

Clinical Use According to Guidelines

• The American Diabetes Association 2024 guidelines recommend PCSK9 inhibitors like evolocumab for patients aged 40-75 years with diabetes and ASCVD who are on high-intensity statin therapy with LDL cholesterol ≥70 mg/dL 2
• High-intensity statin therapy should be maximized first, and the decision to add evolocumab should follow a clinician-patient discussion about net benefit, safety, and cost 2
• For patients with statin intolerance (partial or complete inability to tolerate statins), evolocumab can be added to maximum tolerated statin therapy or used in combination with other non-statin therapies 2

Safety Profile

• Evolocumab was generally well-tolerated with no significant difference in adverse events compared to placebo, except for injection-site reactions (2.1% vs 1.6%) 3
• No increased risk of new-onset diabetes or neurocognitive events was observed in clinical trials 3
• No dose adjustment is needed in patients with renal impairment or mild to moderate hepatic impairment (Child-Pugh A or B) 1
• The medication can be used in pediatric patients aged 10 years and older with HeFH or HoFH 1

Important Clinical Considerations

• Evolocumab is approved as adjunctive therapy to maximally tolerated statin therapy, not as monotherapy replacement for statins in most patients (though it can be used in statin-intolerant patients) 2, 1
• Prior authorization typically requires documentation of established ASCVD or familial hypercholesterolemia, evidence of maximally tolerated statin therapy, and current LDL-C levels above target 5
• Alirocumab (Praluent) is a direct alternative PCSK9 inhibitor with similar efficacy and mechanism of action, reducing LDL-C by 45-58% 6
• The absolute bioavailability following subcutaneous administration is 72%, with median peak serum concentrations attained in 3 to 4 days 1