Evolocumab, sold by Amgen as Repatha, is a human monoclonal antibody that lowers LDL cholesterol (low-density lipoprotein, the main cholesterol-carrying particle linked to clogged arteries). It works by blocking PCSK9, a liver protein that destroys LDL receptors. It is given as an injection under the skin every 2 weeks or once a month, usually on top of a statin.
The FDA first approved it in August 2015 and added a heart-attack and stroke prevention indication in December 2017, after the FOURIER outcomes trial (Drugs@FDA). In trials it lowered LDL-C by roughly 55–71% more than placebo when added to background therapy. A second outcomes trial, VESALIUS-CV, published in 2025–2026, found fewer first heart attacks and strokes in high-risk people who had never had one (Bohula et al., NEJM 2026).
People who use testosterone or anabolic steroids sometimes ask about it because these drugs can push LDL-C and apo B up and HDL-C down. No trial has tested evolocumab in anabolic steroid users. This page summarizes what the FDA label, the outcome trials and the published steroid-lipid studies report. It is for education only and is not medical advice.
| Property | Detail |
|---|---|
| Drug class | PCSK9 inhibitor; human IgG2 monoclonal antibody |
| Brand / approval | Repatha (Amgen), BLA 125522; FDA approved August 27, 2015 |
| Route | Subcutaneous injection (abdomen, thigh or upper arm) |
| Strength | 140 mg/mL in single-dose prefilled pens, autoinjectors and syringes |
| Labeled adult dose | 140 mg every 2 weeks or 420 mg once monthly |
| LDL-C lowering (label) | About 55–71% more than placebo at week 12 in adults with hypercholesterolemia |
| Half-life (label) | Effective half-life 11–17 days |
| Key mechanism | Blocks PCSK9 so more LDL receptors stay on liver cells and clear LDL from the blood |
| US status | Prescription only; not a controlled substance |
| WADA status | Not named on the WADA 2026 Prohibited List |
What it is
Evolocumab is a human monoclonal immunoglobulin G2 (IgG2) antibody with a molecular weight of about 144 kDa. It is produced in genetically engineered Chinese hamster ovary cells (FDA label). Each 1 mL dose contains 140 mg of evolocumab in a preservative-free solution of proline, acetate and polysorbate 80.
PCSK9 (proprotein convertase subtilisin/kexin type 9) is a protein released by the liver. It binds the LDL receptor on liver cells and sends it to be broken down, so fewer receptors return to the cell surface. Evolocumab binds circulating PCSK9 and stops it from attaching to the receptor. More LDL receptors stay available, and the liver pulls more LDL out of the blood (FDA label).
This makes it a different tool from the other common LDL drugs:
| Drug | How it lowers LDL-C | Form |
|---|---|---|
| Statins, e.g. atorvastatin and rosuvastatin | Block cholesterol synthesis in the liver (HMG-CoA reductase), which raises LDL receptor numbers | Daily oral tablet |
| Ezetimibe | Blocks cholesterol absorption in the gut | Daily oral tablet |
| Evolocumab | Stops PCSK9 from degrading LDL receptors | Injection every 2 weeks or monthly |
The two are usually combined rather than swapped: in FOURIER, 69% of patients were on a high-intensity and 30% on a moderate-intensity statin at baseline (FDA label).
Pharmacokinetics
Evolocumab has non-linear kinetics because part of its elimination runs through binding to PCSK9 itself. From the label (FDA label):
| Parameter | Value |
|---|---|
| Time to peak after a subcutaneous dose | 3–4 days (median) |
| Absolute bioavailability | 72% |
| Peak level, single 140 mg dose | 18.6 µg/mL (mean) |
| Peak level, single 420 mg dose | 59.0 µg/mL (mean) |
| Volume of distribution (420 mg IV) | 3.3 L |
| Effective half-life | 11–17 days |
| Steady state | Trough levels approach steady state by 12 weeks; about 2–3× accumulation |
| Maximum suppression of free PCSK9 | By 4 hours after a dose |
| Maximum LDL-C reduction | By 2 weeks (140 mg) or 3 weeks (420 mg) after a single dose |
Two elimination routes operate. At low concentrations the antibody is cleared mainly by binding to PCSK9 (a saturable, target-mediated route). At higher concentrations it is broken down like other antibodies by protein degradation.
Other points from the label:
- Kidneys: monoclonal antibodies are not known to be eliminated by the kidneys, and no dose change is needed for kidney impairment. In severe kidney disease or dialysis, drug exposure was lower but PCSK9 reduction was similar.
- Liver: mild to moderate liver impairment lowered peak levels by 20–30% and total exposure by 40–50%; no dose change is needed. There are no data in severe liver impairment.
- Statins: high-intensity statin therapy lowered evolocumab levels by about 20%, which the label calls not clinically meaningful.
- Body weight: exposure falls as body weight rises, but the difference is not clinically meaningful.
Approved medical use
The current US label (revised 07/2026) approves Repatha (FDA label):
- to reduce the risk of major cardiovascular events (cardiovascular death, heart attack, stroke, unstable angina needing hospital care, or coronary revascularization) in adults at increased risk for these events;
- with diet and exercise, to lower LDL-C in adults with hypercholesterolemia (high blood cholesterol);
- with diet and exercise, to lower LDL-C in adults and children aged 10 and older with heterozygous familial hypercholesterolemia (HeFH, an inherited cause of very high LDL);
- with diet and exercise, to lower LDL-C in adults and children aged 10 and older with homozygous familial hypercholesterolemia (HoFH, the rare and severe double-inherited form).
The cardiovascular indication was first added on December 1, 2017, for adults with established cardiovascular disease (FDA approval letter, 2017). On August 21, 2025, FDA approved a supplement that revised the indication wording (FDA approval letter, 2025). The label’s clinical studies section still describes FOURIER as its outcomes trial.
Labeled dosing
| Population | Labeled dose |
|---|---|
| Adults at increased cardiovascular risk or with hypercholesterolemia | 140 mg every 2 weeks or 420 mg once monthly |
| Adults and children 10 and older with HeFH | 140 mg every 2 weeks or 420 mg once monthly |
| Adults and children 10 and older with HoFH | 420 mg once monthly; may increase to 420 mg every 2 weeks if no meaningful response by 12 weeks |
| Patients on lipid apheresis | May start at 420 mg every 2 weeks, given after the apheresis session |
The label notes that LDL-C lowering can be measured as early as 4 weeks after starting. With the once-monthly dose, LDL-C can vary through the month, so the label suggests measuring it just before the next dose. The 420 mg dose is given as three 140 mg injections within 30 minutes.
What the research shows
LDL lowering in the label trials
All results below are the difference from placebo (or ezetimibe) in mean percent change from baseline (FDA label):
| Trial (n) | Population and background | Dose | LDL-C vs placebo | Apo B vs placebo |
|---|---|---|---|---|
| LAPLACE-2 (1,896), 12 weeks | Hypercholesterolemia on a statin | 140 mg every 2 weeks | −71% (95% CI −74 to −67) | −55% |
| LAPLACE-2, 12 weeks | Same | 420 mg monthly | −63% (95% CI −68 to −57) | −50% |
| DESCARTES (901), 52 weeks | Diet alone, or atorvastatin with or without ezetimibe | 420 mg monthly | −55% (95% CI −60 to −50) | −40% |
| MENDEL-2 (614), 12 weeks | No lipid-lowering drug; mean baseline LDL-C 143 mg/dL | 140 mg every 2 weeks / 420 mg monthly | −55% / −57% | −45% / −48% |
| RUTHERFORD-2 (329), 12 weeks | HeFH on statins; mean baseline LDL-C 156 mg/dL | 140 mg every 2 weeks / 420 mg monthly | −61% / −60% | −49% / −48% |
| HAUSER-RCT (157), 24 weeks | Children 10–17 with HeFH | 420 mg monthly | −38% (95% CI −45 to −31) | −32% |
| TESLA (49), 12 weeks | HoFH; mean baseline LDL-C 349 mg/dL | 420 mg monthly | −31% (95% CI −44 to −18) | −21% |
Against ezetimibe 10 mg/day, evolocumab lowered LDL-C by a further 41–45% in LAPLACE-2 (on atorvastatin) and 37–38% in MENDEL-2. Non-HDL-C and total cholesterol fell as well. The response is weaker in HoFH because the drug needs working LDL receptors: patients with two receptor-negative genes did not respond in TESLA.
FOURIER: established cardiovascular disease
FOURIER randomized 27,564 adults with prior heart attack, stroke or symptomatic peripheral artery disease and an LDL-C of 70 mg/dL or higher on statin therapy (Sabatine et al., NEJM 2017). Evolocumab cut LDL-C by 59% vs placebo at 48 weeks, from a median of 92 mg/dL to 30 mg/dL. The label reports the following over a median of 26 months (FDA label):
| Outcome | Placebo (n = 13,780) | Evolocumab (n = 13,784) | Hazard ratio (95% CI) |
|---|---|---|---|
| Primary composite (CV death, MI, stroke, unstable angina hospitalization, revascularization) | 11.3% | 9.8% | 0.85 (0.79–0.92) |
| CV death, MI or stroke | 7.4% | 5.9% | 0.80 (0.73–0.88) |
| Heart attack (MI) | 4.6% | 3.4% | 0.73 (0.65–0.82) |
| Stroke | 1.9% | 1.5% | 0.79 (0.66–0.95) |
| Coronary revascularization | 7.0% | 5.5% | 0.78 (0.71–0.86) |
| Cardiovascular death | 1.7% | 1.8% | 1.05 (0.88–1.25) |
| Death from any cause | 3.1% | 3.2% | 1.04 (0.91–1.19) |
So FOURIER showed fewer heart attacks, strokes and procedures, but no difference in deaths over about 2 years. At week 48, median LDL-C on evolocumab was 26 mg/dL, and 47% of patients were under 25 mg/dL.
In the open-label extension (FOURIER-OLE), 6,635 patients took evolocumab for a median of another 5.0 years, up to 8.4 years in total (O’Donoghue et al., Circulation 2022). Those first randomized to evolocumab rather than placebo had a lower risk of the primary composite (HR 0.85, 95% CI 0.75–0.96) and of cardiovascular death (HR 0.77, 95% CI 0.60–0.99) during the extension. Because everyone was on the drug in the extension, this compares early with delayed treatment, not drug with placebo.
VESALIUS-CV: high risk without a prior heart attack or stroke
VESALIUS-CV randomized 12,257 patients with atherosclerosis or high-risk diabetes, no previous heart attack or stroke, and an LDL-C of at least 90 mg/dL to evolocumab 140 mg every 2 weeks or placebo (Bohula et al., NEJM 2026). Median follow-up was 4.6 years.
| Outcome | Placebo | Evolocumab | Hazard ratio (95% CI) |
|---|---|---|---|
| 3-point MACE (coronary death, MI, ischemic stroke) | 8.0% | 6.2% | 0.75 (0.65–0.86) |
| 4-point MACE (adds ischemia-driven revascularization) | 16.2% | 13.4% | 0.81 (0.73–0.89) |
| Death from any cause (prespecified analysis) | 9.7% | 7.9% | 0.80 (0.70–0.91) |
| Cardiovascular death (prespecified analysis) | 3.6% | 2.8% | 0.79 (0.64–0.98) |
Rates for MACE and all-cause death are 5-year Kaplan-Meier estimates. The trial reported no between-group difference in safety events. The mortality figures come from a separate prespecified analysis, which estimated that most of the drop in non-cardiovascular deaths was explained by preventing earlier nonfatal heart events (Giugliano et al., Circulation 2026). In a subgroup of 7,557 patients, evolocumab lowered LDL-C by about 61–67 mg/dL at 48 weeks (Monguillon et al., Circulation 2026).
Plaque and lipoprotein(a)
- Coronary plaque (GLAGOV): 968 statin-treated patients with coronary disease received evolocumab 420 mg monthly or placebo for 76 weeks. Time-averaged LDL-C was 36.6 vs 93.0 mg/dL. Percent atheroma volume, measured by intravascular ultrasound, fell by 0.95% with evolocumab and rose by 0.05% with placebo (difference −1.0%), and 64.3% vs 47.3% of patients showed regression (Nicholls et al., JAMA 2016).
- Lipoprotein(a): Lp(a) is a largely inherited LDL-like particle and an independent risk factor for coronary disease. In FOURIER, evolocumab cut Lp(a) by a median of 26.9% at 48 weeks. Patients with Lp(a) above the median had a larger coronary benefit (HR 0.77 vs 0.93), though the interaction was not significant (p = 0.07) (O’Donoghue et al., Circulation 2019). VESALIUS-CV found a similar relative benefit regardless of baseline Lp(a) (Monguillon et al., Circulation 2026).
Anabolic steroid users
Evolocumab is not approved for, and has not been tested in, people using anabolic-androgenic steroids (AAS). The studies below describe what these hormones do to blood lipids. They explain why the question comes up; they do not show that evolocumab helps in this setting.
| Study | Design and n | Exposure | Lipid findings |
|---|---|---|---|
| Hartgens et al., Br J Sports Med 2004 | Non-blinded study of 19 self-administering strength athletes, plus a randomized trial in 16 bodybuilders | Self-chosen AAS for 8 or 14 weeks; nandrolone decanoate 200 mg/week for 8 weeks in the trial | Self-administered AAS: HDL-C 1.08 to 0.43 mmol/L (≈42 to 17 mg/dL), apo B 0.96 to 1.32 g/L, Lp(a) fell. Changes had not recovered 6 weeks after stopping. Nandrolone alone changed only Lp(a) |
| Smit et al., Andrologia 2022 (HAARLEM) | Prospective cohort, 100 men | Self-administered AAS cycle | During use: LDL-C +0.45 mmol/L (≈17 mg/dL), apo B +18.2 mg/dL, HDL-C −0.40 mmol/L (≈15 mg/dL), Lp(a) −37.6%. Values returned to baseline 3 months after the cycle |
Three points follow from the sources:
- The main AAS effect is on HDL, which evolocumab does not target. The label’s lipid tables report LDL-C, non-HDL-C, apo B and total cholesterol. Evolocumab’s mechanism works on LDL clearance, and no study has measured whether it offsets the HDL fall seen during AAS use.
- Apo B may be the better measure. A 2026 review of cardiovascular prevention in young male androgen abusers suggests apo B or non-HDL-C targets because LDL-C and particle number can diverge in this group. It lists PCSK9 inhibitors, ezetimibe and bempedoic acid as options when statins are not tolerated. It also states that empirical data on lipid or blood-pressure drugs specifically in androgen abusers are currently lacking (Bond et al., Clin Cardiol 2026).
- Only a single case report exists. A transgender man on testosterone with genetically confirmed HeFH, who could not tolerate statins, had LDL-C lowered by about 40% for 23 months on a PCSK9 inhibitor with no reported adverse events (Pirazzi et al., J Endocr Soc 2019). One case cannot establish safety or effect.
Steroid hormones and very low LDL
Cholesterol is the raw material for testosterone, cortisol and other steroid hormones, so a common question is whether very low LDL-C impairs hormone production. In a prespecified analysis of the 12-week BERSON trial, Chinese patients with type 2 diabetes on atorvastatin showed no clinically relevant change in cortisol, ACTH, testosterone (men), estradiol (women), LH or FSH on evolocumab (Blom et al., Endocrinol Diabetes Metab 2020). The study was short and did not include people using exogenous hormones.
Side effects and risks
Repatha has no boxed warning. Its only contraindication is a history of serious hypersensitivity to evolocumab or any ingredient (FDA label).
Common side effects
In the 52-week DESCARTES trial (599 on evolocumab, 302 on placebo), the label lists these as the most common reactions that were more frequent than placebo:
| Reaction | Placebo | Evolocumab 420 mg monthly |
|---|---|---|
| Nasopharyngitis (common cold) | 9.6% | 10.5% |
| Upper respiratory tract infection | 6.3% | 9.3% |
| Influenza | 6.3% | 7.5% |
| Back pain | 5.6% | 6.2% |
| Injection site reactions (redness, pain, bruising) | 5.0% | 5.7% |
| Myalgia (muscle pain) | 3.0% | 4.0% |
Side effects led to stopping treatment in 2.2% on evolocumab vs 1% on placebo. In the pooled trials, injection site reactions occurred in 3.2% vs 3.0%. In FOURIER, injection site reactions were 2.1% vs 1.6% (Sabatine et al., NEJM 2017).
Allergic reactions and latex
- Hypersensitivity: reactions including angioedema (swelling of the face, lips, tongue or throat) have been reported. The label says to stop the drug and treat if a serious reaction occurs.
- Latex: some autoinjector and syringe presentations have dry natural rubber in the needle cover. Latex-free versions are available.
Diabetes and blood sugar
New-onset diabetes was a prespecified safety question. In FOURIER, new-onset diabetes among the 16,676 patients without diabetes was 8.1% on evolocumab vs 7.7% on placebo (FDA label). A prespecified analysis found no significant increase (HR 1.05, 95% CI 0.94–1.17), including in people with prediabetes, and no change in HbA1c or fasting glucose (Sabatine et al., Lancet Diabetes Endocrinol 2017).
Memory and very low LDL-C
Early concerns about cognitive side effects led to the EBBINGHAUS substudy of FOURIER. Among 1,204 patients followed for a median of 19 months, evolocumab was non-inferior to placebo on executive function, with no significant differences in working memory, episodic memory or psychomotor speed (Giugliano et al., NEJM 2017). In FOURIER-OLE, rates of serious adverse events, muscle-related events, new-onset diabetes, hemorrhagic stroke and neurocognitive events over up to 8.4 years did not exceed those in the original placebo group (O’Donoghue et al., Circulation 2022).
Immunogenicity
Anti-drug antibodies developed in 0.3% (48 of 17,992) of treated adults. None were neutralizing, and they did not affect drug levels, response or safety (FDA label).
Pregnancy, breastfeeding and children
- Pregnancy: human data are insufficient. Evolocumab, like other IgG antibodies, crosses the placenta. In monkeys, it caused no effects on pregnancy or infant development at up to 12 times the human exposure. Another PCSK9 antibody caused immune suppression in infant monkeys, and evolocumab was not tested for this.
- Breastfeeding: no data on evolocumab in human milk.
- Children: effectiveness is established only for HeFH and HoFH from age 10.
Interactions
The label has no drug interactions section. The only interaction study it reports is the roughly 20% lower evolocumab exposure with high-intensity statins, which the label calls not clinically meaningful.
Storage
The label states Repatha should be stored refrigerated at 2–8 °C (36–46 °F) in the original carton, not frozen and not shaken. It may be kept at room temperature, 20–25 °C (68–77 °F), for up to 30 days, after which it must be discarded (FDA label).
Key takeaways
- A different route to lower LDL. Evolocumab blocks PCSK9, so liver cells keep more LDL receptors. It is an injectable antibody, usually added to a statin, not a replacement for one.
- Large LDL drops. Label trials showed about 55–71% lower LDL-C than placebo in adults and about 37–45% more than ezetimibe. Apo B fell by about 40–55%.
- Fewer heart attacks and strokes. FOURIER cut cardiovascular death, MI or stroke by 20% but did not change deaths over about 2 years. VESALIUS-CV cut first major events by 25% in high-risk people without a prior heart attack or stroke, and a prespecified analysis found 20% lower all-cause mortality over 4.6 years.
- Few side effects. The most common were colds, respiratory infections and injection site reactions. Trials found no rise in new diabetes or cognitive problems, even at very low LDL-C.
- No data in steroid users. AAS mainly lower HDL and raise apo B. Evolocumab does not target HDL, and no study has tested it in AAS users.
Sources
- Amgen. Repatha (evolocumab) injection, for subcutaneous use. Prescribing information, revised 07/2026. DailyMed.
- Food and Drug Administration. Drugs@FDA: Repatha, BLA 125522, approval history. FDA.
- Food and Drug Administration. Supplement approval letter, BLA 125522/S-013, S-014. December 1, 2017. FDA.
- Food and Drug Administration. Supplement approval letter, BLA 125522/S-045. August 21, 2025. FDA.
- Sabatine MS, Giugliano RP, Keech AC, et al. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med. 2017;376(18):1713–1722. PubMed.
- O’Donoghue ML, Giugliano RP, Wiviott SD, et al. Long-term evolocumab in patients with established atherosclerotic cardiovascular disease. Circulation. 2022;146(15):1109–1119. PubMed.
- Bohula EA, Marston NA, Bhatia AK, et al. Evolocumab in patients without a previous myocardial infarction or stroke. N Engl J Med. 2026;394(2):117–127. PubMed.
- Giugliano RP, Bohula EA, Bellavia A, et al. Effects of evolocumab on mortality outcomes in patients without previous myocardial infarction or stroke: a prespecified analysis of the VESALIUS-CV randomized clinical trial. Circulation. Published online August 31, 2026. PubMed.
- Monguillon V, Marston NA, Bohula EA, et al. Lipoprotein(a) levels, risk of cardiovascular events, and benefit of evolocumab: findings from the VESALIUS-CV trial. Circulation. 2026;153(25):1960–1968. PubMed.
- Nicholls SJ, Puri R, Anderson T, et al. Effect of evolocumab on progression of coronary disease in statin-treated patients: the GLAGOV randomized clinical trial. JAMA. 2016;316(22):2373–2384. PubMed.
- O’Donoghue ML, Fazio S, Giugliano RP, et al. Lipoprotein(a), PCSK9 inhibition, and cardiovascular risk. Circulation. 2019;139(12):1483–1492. PubMed.
- Sabatine MS, Leiter LA, Wiviott SD, et al. Cardiovascular safety and efficacy of the PCSK9 inhibitor evolocumab in patients with and without diabetes and the effect of evolocumab on glycaemia and risk of new-onset diabetes: a prespecified analysis of the FOURIER randomised controlled trial. Lancet Diabetes Endocrinol. 2017;5(12):941–950. PubMed.
- Giugliano RP, Mach F, Zavitz K, et al. Cognitive function in a randomized trial of evolocumab. N Engl J Med. 2017;377(7):633–643. PubMed.
- Blom DJ, Chen J, Yuan Z, et al. Effects of evolocumab therapy and low LDL-C levels on vitamin E and steroid hormones in Chinese and global patients with type 2 diabetes. Endocrinol Diabetes Metab. 2020;3(2):e00123. PubMed.
- Hartgens F, Rietjens G, Keizer HA, Kuipers H, Wolffenbuttel BH. Effects of androgenic-anabolic steroids on apolipoproteins and lipoprotein (a). Br J Sports Med. 2004;38(3):253–259. PubMed.
- Smit DL, Grefhorst A, Buijs MM, et al. Prospective study on blood pressure, lipid metabolism and erythrocytosis during and after androgen abuse. Andrologia. 2022;54(4):e14372. PubMed.
- Bond P, Smit DL, Verdegaal T, de Ronde W. Preventing atherosclerotic cardiovascular disease in young male androgen abusers. Clin Cardiol. 2026;49(2):e70257. PubMed.
- Pirazzi C, Tavaglione F, Tivesten Å, Romeo S. PCSK9 inhibitors in a statin-intolerant transgender man with heterozygous familial hypercholesterolemia: a case report. J Endocr Soc. 2019;3(8):1461–1464. PubMed.
- World Anti-Doping Agency. The 2026 Prohibited List. WADA 2026 Prohibited List.