Prevents PCSK9 from binding LDL receptors, increasing the receptors available to clear LDL. Source
Established atherosclerotic cardiovascular disease with LDL-C at least 70 mg/dL despite statin treatment.
Study contextSelected approval record (2015-08-27): FDA first licensed evolocumab as Repatha. This initial approval preceded the dedicated cardiovascular-outcome results below.
Status sourceStatus & indicationsPrimary cardiovascular composite: HR 0.85 (95% CI 0.79–0.92). Cardiovascular death, heart attack, stroke, hospitalization for unstable angina, or coronary revascularization.
FOURIER · Phase 3 · 140 mg every 2 weeks or 420 mg monthly, subcutaneously · Moderate- or high-intensity statins; evolocumab versus placebo added. · Median randomized follow-up: 2.2 years.
Evidence & limitationsInjection-site reactions: 2.1% versus 1.6%; no significant between-group difference in serious, neurocognitive, or new-diabetes adverse events.
Safety contextJanuary 31, 2027 · Evolocumab subclinical-atheroma trial start, with AI-CCTA plaque-volume outcomes.
Registry estimate; not yet recruiting
Milestone detailsStudy results apply to their own population, dose and analysis. They do not establish a ranking between therapies.
Each result belongs to its own study population, dose and analysis. Open a result for its chart, comparator, safety findings and limitations.
LDL-C: 71 percentage-point reduction vs placebo · 12 weeks
140 mg every 2 weeks
Adults with hypercholesterolemia
Mean change; multiple-imputation model accounts for adherence.
Label risks include hypersensitivity and injection-site reactions.
Limitations: Add-on effect. Baseline LDL-C ranged 77–127 mg/dL across background statin groups; no single pooled baseline is substituted.
Lp(a): 30 percentage-point reduction vs placebo · Average of weeks 10 and 12
140 mg every 2 weeks
Adults with hypercholesterolemia or mixed dyslipidemia
Reported treatment effects: mean percent change to the average of weeks 10 and 12.
Label risks include hypersensitivity and injection-site reactions.
Limitations: Average of two visits, not a measurement at week 11. Kept separate from the FDA week-12 LDL/ApoB results.
Primary cardiovascular composite: HR 0.85 (95% CI 0.79–0.92). Cardiovascular death, heart attack, stroke, hospitalization for unstable angina, or coronary revascularization.
140 mg every 2 weeks or 420 mg monthly, subcutaneously
Established atherosclerotic cardiovascular disease with LDL-C at least 70 mg/dL despite statin treatment.
Background treatment & comparator: Moderate- or high-intensity statins; evolocumab versus placebo added.
Median randomized follow-up: 2.2 years. Crude proportion with an event during randomized follow-up; median randomized follow-up: 2.2 years.
Injection-site reactions: 2.1% versus 1.6%; no significant between-group difference in serious, neurocognitive, or new-diabetes adverse events.
Limitations: The blinded trial did not demonstrate a mortality reduction. Later FOURIER-OLE findings are not mixed into this randomized-period estimate.
Three-point primary composite: HR 0.75 (95% CI 0.65–0.86). Coronary-heart-disease death, heart attack, or ischemic stroke.
140 mg subcutaneously every 2 weeks
Qualifying atherosclerosis or high-risk diabetes, without previous heart attack or stroke; LDL-C at least 90 mg/dL.
Background treatment & comparator: Optimally tolerated lipid therapy; 87% used statins and 20% ezetimibe. Evolocumab versus placebo added.
Median randomized follow-up: 4.6 years. Five-year Kaplan–Meier estimate.
No evidence of a between-group difference in safety-event incidence.
Limitations: No previous heart attack or stroke does not mean no atherosclerosis: 67% had qualifying atherosclerosis. Mortality estimates are prespecified secondary analyses with nominal confidence intervals, from the same randomized follow-up.
Status in this atlas: Selected approval record (2015-08-27): FDA first licensed evolocumab as Repatha. This initial approval preceded the dedicated cardiovascular-outcome results below. Status source
Prevents PCSK9 from binding LDL receptors, increasing the receptors available to clear LDL.
Mechanism sourceMechanism & side effects: PCSK9 antibodies
Uses, doses and availability depend on the formulation, indication and country. Study doses below describe research; they are not prescribing instructions.
Human IgG2 monoclonal antibody directed against PCSK9.
Shown: Recombinant antibody protein.
Protein class is verified from the label. No exact whole-antibody atomic structure has been verified for this bundle; a generic antibody icon would be only a class schematic.
DailyMed Repatha label, sections 11 and 12.1Evolocumab · compound history across indications
Selected sourced milestones, not a complete development history. This selective review adds a planned coronary-plaque trial; historical outcome and biomarker estimates are unchanged. Registration is not trial initiation, and estimated future dates are not readout commitments. The first listed date is not necessarily when development began.
The dose-ranging trial of AMG 145, later named evolocumab, reported substantial LDL-C lowering in 631 statin-treated participants. These early biomarker findings supported phase 3 development.
LAPLACE-TIMI 57 phase 2 results — Lancet; online November 6, 2012The randomized LAPLACE-2 trial reported LDL-C lowering when evolocumab was added to moderate- or high-intensity statins. This is the trial behind the lipid-response estimates plotted here.
LAPLACE-2 randomized clinical trial — JAMA (2014)FDA first licensed evolocumab as Repatha. This initial approval preceded the dedicated cardiovascular-outcome results below.
FDA Purple Book — Repatha original approval dateIn 27,564 people with established cardiovascular disease receiving statins, evolocumab reduced the primary cardiovascular composite. The randomized period did not demonstrate a mortality reduction; this is the FOURIER outcome trial plotted here.
Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease — NEJM (2017)In 12,257 people with atherosclerosis or high-risk diabetes but no previous heart attack or stroke, evolocumab reduced both primary cardiovascular composites. This plotted population includes people with existing atherosclerosis and should not be equated with uniformly disease-free primary prevention.
Evolocumab in Patients without a Previous Myocardial Infarction or Stroke — NEJM (2025)NCT07803679 first appeared on the registry September 4. Its September 21 update lists a planned phase 4 trial of 308 adults with subclinical coronary atheroma: evolocumab plus usual lipid management versus usual management alone, open-label with blinded endpoint assessment. The primary outcome is 72-week noncalcified plaque-volume change on AI-enabled coronary CT angiography. It was not yet recruiting when checked September 27. January 31, 2027 start and April 30, 2029 completion are registry estimates. No results are available; plaque change would not by itself prove fewer cardiovascular events or a benefit from population screening.
ClinicalTrials.gov — NCT07803679; first posted September 4, updated September 21, 2026Selected sources checked Sep 27, 2026. This is not an exhaustive history.