REPATHA

Indications and Usage ( 1 ) 08/2025 Dosage and Administration, Important Administration Instructions ( 2.3 ) 07/2026

1 INDICATIONS AND USAGE REPATHA is indicated: To reduce the risk of major adverse cardiovascular (CV) events (CV death, myocardial infarction, stroke, unstable angina requiring hospitalization, or coronary revascularization) in adults at increased risk for these events. As an adjunct to diet and exercise to reduce low-density lipoprotein cholesterol (LDL-C) in: adults with hypercholesterolemia. adults and pediatric patients aged 10 years and older with heterozygous familial hypercholesterolemia (HeFH). adults and pediatric patients aged 10 years and older with homozygous familial hypercholesterolemia (HoFH). REPATHA is a PCSK9 (proprotein convertase subtilisin kexin type 9) inhibitor indicated: To reduce the risk of major adverse cardiovascular (CV) events (CV death, myocardial infarction, stroke, unstable angina requiring hospitalization, or coronary revascularization) in adults at increased risk for these events. ( 1 ) As an adjunct to diet and exercise to reduce low-density lipoprotein cholesterol (LDL-C) in ( 1 ): adults with hypercholesterolemia. adults and pediatric patients aged 10 years and older with heterozygous familial hypercholesterolemia (HeFH). adults and pediatric patients aged 10 years and older with homozygous familial hypercholesterolemia (HoFH).

2 DOSAGE AND ADMINISTRATION In adults at increased risk for CV events or with hypercholesterolemia : The recommended dosage of REPATHA is either 140 mg every 2 weeks OR 420 mg once monthly administered subcutaneously. ( 2.1 ) If switching dosage regimens, administer the first dose of the new regimen on the next scheduled date of the prior regimen. ( 2.1 ) In adults and pediatric patients aged 10 years and older with HeFH : The recommended dosage of REPATHA is either 140 mg every 2 weeks OR 420 mg once monthly administered subcutaneously. ( 2.1 ) If switching dosage regimens, administer the first dose of the new regimen on the next scheduled date of the prior regimen. ( 2.1 ) In adults and pediatric patients aged 10 years and older with HoFH : The initial recommended dosage of REPATHA is 420 mg once monthly administered subcutaneously. ( 2.1 ) The dosage can be increased to 420 mg every 2 weeks if a clinically meaningful response is not achieved in 12 weeks. ( 2.1 ) Patients on lipid apheresis may initiate treatment with 420 mg every 2 weeks to correspond with their apheresis schedule. Administer REPATHA after the apheresis session is complete. ( 2.1 ) Assess LDL-C when clinically appropriate. The LDL-lowering effect of REPATHA may be measured as early as 4 weeks after initiation. ( 2.1 ) REPATHA is available as prefilled single-dose SureClick ® autoinjectors, and prefilled single-dose syringes that either contain dry natural rubber (a derivative of latex) in the needle cover or are not made with natural rubber latex. Consider prescribing a presentation of REPATHA that does not contain dry natural rubber for individuals that are sensitive to latex. ( 2.3 , 16 ) Administer REPATHA subcutaneously into areas of the abdomen, thigh, or upper arm. Rotate injection sites for each administration. ( 2.3 ) See Full Prescribing Information for important administration instructions. ( 2.3 ) 2.1 Recommended Dosage In adults at increased risk for CV events or with hypercholesterolemia: The recommended dosage of REPATHA is either 140 mg every 2 weeks OR 420 mg once monthly administered subcutaneously [see Dosage and Administration (2.3) ] . If switching dosage regimens, administer the first dose of the new regimen on the next scheduled date of the prior regimen. In adults and pediatric patients aged 10 years and older with HeFH: The recommended dosage of REPATHA is either 140 mg every 2 weeks OR 420 mg once monthly administered subcutaneously [see Dosage and Administration (2.3) ] . If switching dosage regimens, administer the first dose of the new regimen on the next scheduled date of the prior regimen. In adults and pediatric patients aged 10 years and older with HoFH: The initial recommended dosage of REPATHA is 420 mg once monthly administered subcutaneously [see Dosage and Administration (2.3) ] . The dosage can be increased to 420 mg every 2 weeks if a clinically meaningful response is not achieved in 12 weeks. Patients on lipid apheresis may initiate treatment with 420 mg every 2 weeks to correspond with their apheresis schedule. Administer REPATHA after the apheresis session is complete. Assess LDL-C when clinically appropriate. The LDL-lowering effect of REPATHA may be measured as early as 4 weeks after initiation. When monitoring LDL-C for patients receiving REPATHA 420 mg once monthly, note that LDL-C can vary during the dosing interval in some patients; recommend measuring LDL-C just prior to the next scheduled dose [see Clinical Studies (14) ] . 2.2 Missed Doses If a dose is missed: Within 7 days from the missed dose, instruct the patient to administer REPATHA and resume the patient's original schedule. More than 7 days after the missed dose: For an every 2-week dose, instruct the patient to wait until the next dose on the original schedule. For a once-monthly dose, instruct the patient to administer the dose and start a new schedule based on this date. 2.3 Important Administration Instructions REPATHA is available as prefilled s …

3 DOSAGE FORMS AND STRENGTHS REPATHA injection is a clear to opalescent, colorless to pale yellow solution available as follows: 140 mg/mL solution in a prefilled single-dose pen 140 mg/mL solution in a prefilled single-dose SureClick ® autoinjector 140 mg/mL solution in a prefilled single-dose syringe Injection ( 3 ): 140 mg/mL solution prefilled single-dose pen 140 mg/mL solution prefilled single-dose SureClick ® autoinjector 140 mg/mL solution prefilled single-dose syringe

4 CONTRAINDICATIONS REPATHA is contraindicated in patients with a history of a serious hypersensitivity reaction to evolocumab or any of the excipients in REPATHA. Serious hypersensitivity reactions including angioedema have occurred in patients treated with REPATHA [see Warnings and Precautions (5.1) ] . Patients with a history of a serious hypersensitivity reaction to evolocumab or any of the excipients in REPATHA. ( 4 )

6 ADVERSE REACTIONS The following adverse reactions are also discussed in other sections of the label: Hypersensitivity Reactions [see Warnings and Precautions (5.1) ] Common (> 5% of patients treated with REPATHA and more frequently than placebo) adverse reactions in adults with: Primary hypercholesterolemia: nasopharyngitis, upper respiratory tract infection, influenza, back pain, and injection site reactions. ( 6 ) Established CV Disease: diabetes mellitus, nasopharyngitis and upper respiratory tract infection. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Amgen Medical Information at 1-800-77-AMGEN (1-800-772-6436) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. Adverse Reactions in Adults with Primary Hypercholesterolemia The data described below reflect exposure to REPATHA in 8 placebo-controlled trials that included 2651 patients treated with REPATHA, including 557 exposed for 6 months and 515 exposed for 1 year (median treatment duration of 12 weeks). The mean age of the population was 57 years, 49% of the population were women, 85% White, 6% Black, 8% Asian, and 2% other races. Adverse Reactions in a 52 - Week Controlled Trial In a 52-week, double-blind, randomized, placebo-controlled trial, 599 patients received 420 mg of REPATHA subcutaneously once monthly [see Clinical Studies (14) ] . The mean age was 56 years (range: 22 to 75 years), 23% were older than 65 years, 52% women, 80% White, 8% Black, 6% Asian; 6% identified as Hispanic ethnicity. Adverse reactions reported in at least 3% of REPATHA-treated patients, and more frequently than in placebo-treated patients are shown in Table 1. Adverse reactions led to discontinuation of treatment in 2.2% of REPATHA-treated patients and 1% of placebo-treated patients. The most common adverse reaction that led to REPATHA treatment discontinuation and occurred at a rate greater than placebo was myalgia (0.3% versus 0% for REPATHA and placebo, respectively). Table 1. Adverse Reactions Occurring in ≥ 3% of REPATHA-treated Patients and More Frequently than with Placebo in a 52-Week Trial Placebo (N = 302) % REPATHA (N = 599) % Nasopharyngitis 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 includes erythema, pain, bruising 5.0 5.7 Cough 3.6 4.5 Urinary tract infection 3.6 4.5 Sinusitis 3.0 4.2 Headache 3.6 4.0 Myalgia 3.0 4.0 Dizziness 2.6 3.7 Musculoskeletal pain 3.0 3.3 Hypertension 2.3 3.2 Diarrhea 2.6 3.0 Gastroenteritis 2.0 3.0 Adverse Reactions in Seven Pooled 12 - Week Controlled Trials In seven pooled 12-week, double-blind, randomized, placebo-controlled trials, 993 patients received 140 mg of REPATHA subcutaneously every 2 weeks and 1059 patients received 420 mg of REPATHA subcutaneously monthly. The mean age was 57 years (range: 18 to 80 years), 29% were older than 65 years, 49% women, 85% White, 5% Black, 9% Asian; 5% identified as Hispanic ethnicity. Adverse reactions reported in at least 1% of REPATHA-treated patients, and more frequently than in placebo-treated patients, are shown in Table 2. Table 2. Adverse Reactions Occurring in ≥ 1% of REPATHA-treated Patients and More Frequently than with Placebo in Pooled 12-Week Trials Placebo (N = 1224) % REPATHA 140 mg every 2 weeks and 420 mg once monthly combined (N = 2052) % Nasopharyngitis 3.9 4.0 Back pain 2.2 2.3 Upper respiratory tract infection 2.0 2.1 Arthralgia 1.6 1.8 Nausea 1.2 1.8 Fatigue 1.0 1.6 Muscle spasms 1.2 1.3 Urinary tract infection 1.2 1.3 Cough 0.7 1.2 Influenza 1.1 1.2 Contusion 0.5 1.0 Adverse Reactions in Eight Pooled Controlled Trials (Seven 12 - Week Trials and One 52 - Week Trial) The adverse reactions described below are …

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Risk Summary Available data from clinical trials and postmarketing reports on REPATHA use in pregnant women are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. In animal reproduction studies, there were no effects on pregnancy or neonatal/infant development when monkeys were subcutaneously administered evolocumab from organogenesis through parturition at dose exposures up to 12 times the exposure at the maximum recommended human dose of 420 mg every month. In a similar study with another drug in the PCSK9 inhibitor antibody class, humoral immune suppression was observed in infant monkeys exposed to that drug in utero at all doses. The exposures where immune suppression occurred in infant monkeys were greater than those expected clinically. No assessment for immune suppression was conducted with evolocumab in infant monkeys. Measurable evolocumab serum concentrations were observed in the infant monkeys at birth at comparable levels to maternal serum, indicating that evolocumab, like other IgG antibodies, crosses the placental barrier. Monoclonal antibodies are transported across the placenta in increasing amounts especially near term; therefore, evolocumab has the potential to be transmitted from the mother to the developing fetus. The estimated background risk of major birth defects and miscarriage for the indicated population(s) is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. There is a pregnancy safety study for REPATHA. If REPATHA is administered during pregnancy, healthcare providers should report REPATHA exposure by contacting Amgen at 1-800-77-AMGEN (1-800-772-6436) or https://wwwext.amgen.com/products/global-patient-safety/adverse-event-reporting. Data Animal Data In cynomolgus monkeys, no effects on embryo-fetal or postnatal development (up to 6 months of age) were observed when evolocumab was dosed during organogenesis to parturition at 50 mg/kg once every 2 weeks by the subcutaneous route at exposures 30- and 12-fold the recommended human doses of 140 mg every 2 weeks and 420 mg once monthly, respectively, based on plasma AUC. No test of humoral immunity in infant monkeys was conducted with evolocumab. 8.2 Lactation Risk Summary There is no information regarding the presence of evolocumab in human milk, the effects on the breastfed infant, or the effects on milk production. Human IgG is present in human milk, but published data suggest that breast milk antibodies do not enter the neonatal and infant circulation in substantial amounts. The development and health benefits of breastfeeding should be considered along with the mother's clinical need for REPATHA and any potential adverse effects on the breastfed infant from REPATHA or from the underlying maternal condition. 8.4 Pediatric Use The safety and effectiveness of REPATHA in combination with diet and other LDL-C-lowering therapies for the treatment of HoFH have been established in pediatric patients aged 10 years and older. Use of REPATHA for this indication is supported by evidence from an adequate and well-controlled trial in adults and pediatric patients aged 13 years and older with HoFH (including 7 pediatric patients treated with REPATHA) and from open-label studies which included an additional 19 pediatric patients aged 11 years and older with HoFH not previously treated with REPATHA [see Adverse Reactions (6.1) and Clinical Studies (14) ] . The safety and effectiveness of REPATHA as an adjunct to diet and other LDL-C-lowering therapies for the treatment of HeFH have been established in pediatric patients aged 10 years and older. Use of REPATHA for this indication is based on data from a 24-week, randomized, placebo-controlled, double-blind trial in pediatric patients with HeFH. In the trial, 104 p …

12.1 Mechanism of Action Evolocumab is a human monoclonal IgG2 directed against human proprotein convertase subtilisin kexin type 9 (PCSK9). PCSK9 binds to the low-density lipoprotein receptor (LDLR) on the surface of hepatocytes to promote LDLR degradation within the liver. By inhibiting the binding of PCSK9 to LDLR, evolocumab increases the number of LDLRs available to clear LDL from the blood, thereby lowering LDL-C levels.

11 DESCRIPTION Evolocumab is a human monoclonal immunoglobulin G2 (IgG2) directed against human proprotein convertase subtilisin kexin type 9 (PCSK9). Evolocumab has an approximate molecular weight (MW) of 144 kDa and is produced in genetically engineered mammalian (Chinese hamster ovary) cells. REPATHA is a sterile, preservative-free, clear to opalescent, colorless to pale yellow solution for subcutaneous use. Each 1 mL prefilled single-dose pen, prefilled single-dose SureClick ® autoinjector and prefilled single-dose syringe contains 140 mg evolocumab, acetate (1.2 mg), polysorbate 80 (0.1 mg), proline (25 mg) in Water for Injection, USP. Sodium hydroxide may be used to adjust to a pH of 5.0.

16 HOW SUPPLIED/STORAGE AND HANDLING REPATHA is a clear to opalescent, colorless to pale yellow solution supplied as follows: Not Made with Natural Rubber Latex – Strength Packaging Unit NDC 140 mg/mL prefilled single-dose pen Carton of 2 72511-143-02 140 mg/mL prefilled single-dose pen Carton of 1 72511-143-01 140 mg/mL prefilled single-dose SureClick ® autoinjector Carton of 2 72511-393-02 140 mg/mL prefilled single-dose SureClick ® autoinjector Carton of 1 72511-393-01 140 mg/mL prefilled single-dose syringe Carton of 1 72511-501-01 Contains Dry Natural Rubber – Strength Packaging Unit NDC 140 mg/mL prefilled single-dose SureClick ® autoinjector The needle cover of the glass prefilled single-dose SureClick ® autoinjector and prefilled single-dose syringe contain dry natural rubber (a derivative of latex) that may cause allergic reactions in individuals sensitive to latex [see Warnings and Precautions (5.1) ] . Carton of 2 72511-760-02 140 mg/mL prefilled single-dose syringe Carton of 1 72511-750-01 Store refrigerated at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light. Do not freeze. Do not shake. REPATHA prefilled single-dose pen, prefilled single-dose SureClick ® autoinjector, or prefilled single-dose syringe may also be kept at room temperature at 68°F to 77°F (20°C to 25°C) in the original carton for 30 days. If not used within the 30 days, discard REPATHA.