Evolocumab

(Repatha®)

Evolocumab

Drug updated on 10/31/2024

Dosage FormInjection (subcutaneous; 140 mg/mL, 420 mg/3.5 mL)
Drug ClassPCSK9 (Proprotein Convertase Subtilisin Kexin Type 9) inhibitors
Ongoing and
Completed Studies
ClinicalTrials.gov

Indication

  • Indicate in adults with established cardiovascular disease (CVD) to reduce the risk of myocardial infarction, stroke, and coronary revascularization in adults with established cardiovascular disease (CVD)
  • Indicated as an adjunct to diet, alone or in combination with other low-density lipoprotein cholesterol (LDL-C)-lowering therapies, in adults with primary hyperlipidemia, including heterozygous familial hypercholesterolemia (HeFH), to reduce LDL-C
  • Indicated 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
  • Indicated 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.

Latest News

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Summary
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  • This summary is based on the review of 31 systematic review(s)/meta-analysis(es). [1-31]
  • Low-Density Lipoprotein (LDL-C) Reduction: Evolocumab significantly reduced LDL-C levels by -61.09% to -63.67% compared to placebo over a median of 24 weeks, with the 140 mg Q2W dosage showing the highest efficacy at -69.13%. Alirocumab showed reductions ranging from -46.35% to -59.75% in various studies.
  • Cardiovascular Outcomes: Evolocumab reduced the risk of myocardial infarction (OR (odds ratio) 0.72, 95% CI (confidence interval): 0.64-0.81, p<0.01), stroke (OR 0.79, 95% CI: 0.66-0.94, p=0.01), and overall major adverse cardiovascular events (MACE) (OR 0.85, 95% CI: 0.80-0.89, p<0.01). Alirocumab was associated with a significant reduction in cardiovascular mortality (OR 0.35, 95% CI: 0.16-0.77, p=0.01) and all-cause mortality (OR 0.60, 95% CI: 0.43-0.84, p<0.01).
  • Subgroup Analysis: PCSK9 (Proprotein convertase subtilisin/kexin type 9) inhibitors effectively reduced LDL-C and MACE in various subgroups, including patients with diabetes mellitus, where a reduction in MACE by 18% was noted. No significant differences in LDL-C reduction were found based on racial or ethnic backgrounds, although Asian participants with type 2 diabetes showed a larger reduction.
  • Chronic Kidney Disease (CKD): PCSK9 inhibitors demonstrated safety and efficacy in lowering LDL-C levels in patients with CKD, but further investigation is required for severe and end-stage CKD populations.
  • General Safety Profile: PCSK9 inhibitors, including evolocumab, alirocumab, and inclisiran, demonstrated favorable safety profiles with no significant increase in the incidence of adverse events (AEs) or severe adverse events (SAEs) compared to placebo. There were no significant differences noted in rates of diabetes, neurocognitive disorders, or serious infections.
  • Injection-Site Reactions and Specific Concerns: Injection-site reactions were more frequently reported with alirocumab, inclisiran, and tafolecimab, while evolocumab did not show an increased risk of sepsis or severe infections. Additionally, alirocumab was associated with a reduction in serious adverse events and diabetes-related adverse events compared to controls.
  • Subgroup Analysis: Among patients with familial hypercholesterolemia, there was no significant difference in treatment-emergent adverse events (TEAEs) and SAEs compared to placebo. However, evolocumab exhibited a slightly higher event rate of AEs in patients with impaired kidney function.
  • Diverse Patient Populations: PCSK9 inhibitors, including evolocumab and alirocumab, effectively reduced LDL-C and MACE in various populations, such as patients with atherosclerotic cardiovascular disease (ASCVD) and those with diabetes mellitus, achieving an 18% reduction in MACE. Both drugs demonstrated efficacy in familial hypercholesterolemia (FH) patients, with no significant differences between heterozygous and homozygous forms, while Asian participants with type 2 diabetes showed larger reductions in LDL-C levels.

Product Monograph / Prescribing Information

Document TitleYearSource
Repatha (evolocumab) Prescribing Information.2021Amgen Inc., Thousand Oaks, CA

Systematic Reviews / Meta-Analyses

Document TitleYearSource
The efficacy and safety of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors combined with statins in patients with hypercholesterolemia: a network meta-analysis2024Frontiers in Cardiovascular Medicine
Novel Low-Density Lipoprotein Cholesterol Reduction Therapies for the Secondary Prevention of Cardiovascular Disease2023Reviews in Cardiovascular Medicine
Proprotein convertase subtilisn/kexin type 9 inhibitors and small interfering RNA therapy for cardiovascular risk reduction: A systematic review and meta-analysis2023PLoS One
PCSK-9 Inhibitors and Cardiovascular Outcomes: A Systematic Review With Meta-Analysis2023Cureus
Impact of alirocumab/evolocumab on lipoprotein (a) concentrations in patients with familial hypercholesterolaemia: a systematic review and meta-analysis of randomized controlled trials2023Endokrynologia Polska
Safety and Effectiveness of Evolocumab During Acute and Sub-acute Phases of Acute Coronary Syndrome (ACS): A Systematic Review and Meta-analysis2023Cureus
The efficacy of PCSK9 inhibitors on major cardiovascular events and lipid profile in patients with diabetes: a systematic review and meta-analysis of randomized controlled trials2023European Heart Journal
Effect of Different Types and Dosages of Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors on Lipoprotein(a) Levels: A Network Meta-analysis2023Journal of Cardiovascular Pharmacology
The Association Between PCSK9 Inhibitor Use and Sepsis: A Systematic Review and Meta-Analysis of 20 Double-Blind, Randomized, Placebo-Controlled Trials2023The American Journal of Medicine
Reduction of Cardiovascular Risk Using Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors in Patients With Acute Coronary Syndrome: A Systematic Review2023Cureus
An Updated Meta-Analysis for Safety Evaluation of Alirocumab and Evolocumab as PCSK9 Inhibitors2023Cardiovascular Therapeutics
Additive effects of ezetimibe, evolocumab, and alirocumab on plaque burden and lipid content as assessed by intravascular ultrasound: A PRISMA-compliant meta-analysis2022Medicine
Exploring the Efficacy of Alirocumab and Evolocumab in Reducing Low-Density Lipoprotein (LDL) Cholesterol Levels in Patients With Familial Hypercholesterolemia: A Systematic Review2022Cureus
A Systematic Review on the Safety and Efficacy of PCSK9 Inhibitors in Lowering Cardiovascular Risks in Patients With Chronic Kidney Disease2022Cureus
Network Meta-Analysis of Randomized Trials Evaluating the Comparative Efficacy of Lipid-Lowering Therapies Added to Maximally Tolerated Statins for the Reduction of Low-Density Lipoprotein Cholesterol2022Journal of the American Heart Association
The promising novel therapies for familial hypercholesterolemia2022Journal of Clinical Laboratory Analysis
PCSK9 inhibitors for secondary prevention in patients with cardiovascular diseases: a bayesian network meta-analysis2022Cardiovascular Diabetology
Effect of PCSK9 Inhibitor on Blood Lipid Levels in Patients with High and Very-High CVD Risk: A Systematic Review and Meta-Analysis2022Cardiology Research and Practice
Efficacy and Safety of Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors as Adjuvant Treatments for Patients with Hypercholesterolemia Treated with Statin: A Systematic Review and Network Meta-analysis2022Frontiers in Pharmacology
Latest clinical evidence about the effect of PCSK9 monoclonal antibodies in patients with familial hypercholesterolaemia: an updated meta-analysis2022Endokrynologia Polska
A meta-analysis of medications directed against PCSK9 in familial hypercholesterolemia2021Atherosclerosis
Effects of Evolocumab on Low-Density Lipoprotein Cholesterol, Non-High Density Lipoprotein Cholesterol, Apolipoprotein B, and Lipoprotein(a) by Race and Ethnicity: A Meta-Analysis of Individual Participant Data From Double-Blind and Open-Label Extension Studies2021Journal of the American Heart Association
Indirect comparison of the efficacy and safety of alirocumab and evolocumab: a systematic review and network meta-analysis2021European Heart Journal
Lipid-lowering Drugs and Neurocognitive Function: A Systematic Review2020In Vivo (Athens, Greece)
PCSK9 monoclonal antibodies for the primary and secondary prevention of cardiovascular disease2020The Cochrane Database of Systematic Reviews
Serious adverse events and deaths in PCSK9 inhibitor trials reported on ClinicalTrials.gov: a systematic review2020Expert Review of Clinical Pharmacology
Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors and Ezetimibe on Risk of New-Onset Diabetes: A Systematic Review and Meta-Analysis of Large, Double-Blinded Randomized Controlled Trials2020Journal of Cardiovascular Pharmacology and Therapeutics
The Effect of PCSK9 (Proprotein Convertase Subtilisin/Kexin Type 9) Inhibition on the Risk of Venous Thromboembolism2020Circulation
Efficacy and Safety of PCSK9 Monoclonal Antibodies in Patients at High Cardiovascular Risk: An Updated Systematic Review and Meta-Analysis of 32 Randomized Controlled Trials2020Advances in therapy
PCSK9 inhibitors and cardiovascular outcomes2020Expert Opinion On Biological therapy
Cholesterol Lowering and Stroke: No Longer Room for Pleiotropic Effects of Statins - Confirmation from PCSK9 Inhibitor Studies2020The American Journal of Medicine

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