FASENRA

Indications and Usage ( 1.3 ) 05/2026 Dosage and Administration ( 2.3 ) 05/2026

1 INDICATIONS AND USAGE FASENRA is an interleukin-5 receptor alpha-directed cytolytic monoclonal antibody (IgG1, kappa) indicated for: • add-on maintenance treatment of adult and pediatric patients aged 6 years and older with severe asthma, and with an eosinophilic phenotype. ( 1.1 ) • treatment of adult patients with eosinophilic granulomatosis with polyangiitis (EGPA). ( 1.2 ) • treatment of adult and pediatric patients aged 12 years and older with hypereosinophilic syndrome (HES) without an identifiable non-hematologic secondary cause. ( 1.3 ) Limitations of Use : Not for relief of acute bronchospasm or status asthmaticus. (1.1) 1.1 Asthma FASENRA is indicated for the add-on maintenance treatment of adult and pediatric patients aged 6 years and older with severe asthma, and with an eosinophilic phenotype. Limitations of Use: • FASENRA is not indicated for the relief of acute bronchospasm or status asthmaticus. 1.2 Eosinophilic Granulomatosis with Polyangiitis FASENRA is indicated for the treatment of adult patients with eosinophilic granulomatosis with polyangiitis (EGPA). 1.3 Hypereosinophilic Syndrome FASENRA is indicated for the treatment of adult and pediatric patients aged 12 years and older with hypereosinophilic syndrome (HES) without an identifiable non-hematologic secondary cause.

2 DOSAGE AND ADMINISTRATION Administer by subcutaneous injection. ( 2.4 ) Asthma Adult and Pediatric Patients 12 Years of Age and Older: • Recommended dosage is 30 mg every 4 weeks for first 3 doses followed by once every 8 weeks thereafter. ( 2.1 ) Pediatric Patients 6 Years to 11 Years of Age: • Weighing Less Than 35 kg : the recommended dosage is 10 mg every 4 weeks for first 3 doses followed by once every 8 weeks thereafter. ( 2.1 ) • Weighing 35 kg or More : the recommended dosage is 30 mg every 4 weeks for first 3 doses followed by once every 8 weeks thereafter. ( 2.1 ) EGPA and HES • Recommended dosage is 30 mg every 4 weeks. ( 2.2 , 2.3 ) See full prescribing information for administration instructions of FASENRA prefilled syringe and FASENRA PEN. ( 2.4 , 2.5 , 2.6 ) 2.1 Recommended Dosage for Asthma Adult and Pediatric Patients 12 Years of Age and Older The recommended dosage of FASENRA is 30 mg (one injection) administered subcutaneously every 4 weeks for the first 3 doses, and then every 8 weeks thereafter. Pediatric Patients 6 to 11 Years of Age The recommended dosage of FASENRA for pediatric patients 6 to 11 years of age is based on body weight as provided in Table 1 . Table 1. Recommended Dosage of FASENRA in Pediatric Patients 6 to 11 Years of Age with Asthma Body weight Recommended Dosage Less than 35 kg 10 mg (one injection) administered subcutaneously every 4 weeks for the first 3 doses, and then every 8 weeks thereafter. 35 kg or more 30 mg (one injection) administered subcutaneously every 4 weeks for the first 3 doses, and then every 8 weeks thereafter. 2.2 Recommended Dosage for EGPA The recommended dosage of FASENRA is 30 mg (one injection) administered subcutaneously once every 4 weeks. 2.3 Recommended Dosage for HES The recommended dosage of FASENRA is 30 mg (one injection) administered subcutaneously once every 4 weeks. 2.4 General Administration Instructions FASENRA is for subcutaneous use only. FASENRA is intended for use under the guidance of a healthcare provider. In line with clinical practice, monitoring of patients after administration of biologic agents is recommended [see Warnings and Precautions (5.1) ] . Administer FASENRA into the thigh or abdomen. The upper arm can also be used if a healthcare provider or caregiver administers the injection. Prior to administration, warm FASENRA by leaving carton at room temperature up to 77°F (25°C) for about 30 minutes. Visually inspect FASENRA for particulate matter and discoloration prior to administration. FASENRA is clear to opalescent, colorless to slightly yellow, and may contain a few translucent or white to off-white particles. Do not use FASENRA if the liquid is cloudy, discolored, or if it contains large particles or foreign particulate matter. Prefilled Syringe The prefilled syringe is for administration by a healthcare provider. Autoinjector (FASENRA PEN®) FASENRA PEN is intended for administration by patients/caregivers. Patients/caregivers may inject after proper training in subcutaneous injection technique, and after the healthcare provider determines it is appropriate. In asthma patients aged 6 to 11 years weighing 35 kg or more, FASENRA PEN should only be administered by a caregiver or healthcare provider. 2.5 Instructions for Administration of FASENRA Prefilled Syringe (Healthcare Providers) Figure 1 FASENRA Prefilled Syringes Prefilled Syringe Components To prepare FASENRA prefilled syringe for subcutaneous administration, carefully read and adhere to these instructions for use. FASENRA is available in a 10 mg and a 30 mg prefilled syringe. Check the labels on the FASENRA carton and prefilled syringe to ensure the correct 10 mg or 30 mg product is being used ( Figure 1 ). Refer to Figure 1 to identify the prefilled syringe components for use in the administration steps. Do not touch the needle guard activation clips to prevent premature activation of the needle safety guard. 1 Grasp the syringe body, not the plunger, to remove prefille …

3 DOSAGE FORMS AND STRENGTHS Injection: clear to opalescent, colorless to slightly yellow solution and may contain a few translucent or white to off‐white particles available as: • 10 mg/0.5 mL solution in a single-dose prefilled syringe. • 30 mg/mL solution in a single-dose prefilled syringe. • 30 mg/mL solution in a single-dose autoinjector FASENRA PEN. Injection: • 10 mg/0.5 mL solution in a single-dose prefilled syringe. ( 3 ) • 30 mg/mL solution in a single-dose prefilled syringe. (3) • 30 mg/mL solution in a single-dose autoinjector FASENRA PEN. (3)

4 CONTRAINDICATIONS FASENRA is contraindicated in patients who have known hypersensitivity to benralizumab or any of its excipients [see Warnings and Precautions (5.1) ] . Known hypersensitivity to benralizumab or excipients. (4)

6 ADVERSE REACTIONS The following adverse reactions are described in greater detail in other sections: • Hypersensitivity Reactions [see Warnings and Precautions (5.1) ] Most common adverse reactions (incidence greater than or equal to 5%): • Asthma: headache and pharyngitis. ( 6.1 ) • EGPA: headache. ( 6.1 ) • HES: headache, hypersensitivity reactions, and influenza-like illness. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact AstraZeneca at 1-800-236-9933 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 practice. Adult and Pediatric Patients 12 Years of Age and Older with Asthma Across three clinical trials (SIROCCO, CALIMA, and ZONDA) for asthma, 1,808 patients received at least 1 dose of FASENRA [see Clinical Studies (14.1) ] . The data described below reflect exposure to FASENRA in 1,663 patients, including 1,556 exposed for at least 24 weeks and 1,387 exposed for at least 48 weeks. The safety exposure for FASENRA is derived from two Phase 3 placebo-controlled trials (SIROCCO and CALIMA) from 48 weeks duration [FASENRA every 4 weeks (n=841), FASENRA every 4 weeks for 3 doses, then every 8 weeks (n=822), and placebo (n=847)]. While a dosing regimen of FASENRA every 4 weeks was included in clinical trials, FASENRA administered every 4 weeks for 3 doses, then every 8 weeks thereafter is the recommended dose [ see Dosage and Administration (2.1) ] . The population studied was 12 to 75 years of age, of which 64% were female and 79% were White. Adverse reactions that occurred at greater than or equal to 3% incidence are shown in Table 2 . Table 2. Adverse Reactions with FASENRA with Greater than or Equal to 3% Incidence in Patients with Asthma (SIROCCO and CALIMA) Adverse Reactions FASENRA (N=822) % Placebo (N=847) % Headache 8 6 Pyrexia 3 2 Pharyngitis Pharyngitis was defined by the following terms: ‘Pharyngitis’, ‘Pharyngitis bacterial’, ‘Viral pharyngitis’, ‘Pharyngitis streptococcal’. 5 3 Hypersensitivity reactions Hypersensitivity Reactions were defined by the following terms: ‘Urticaria’, ‘Urticaria papular’, and ‘Rash’ [see Warnings and Precautions (5.1) ] . 3 3 28-Week Trial Adverse reactions from ZONDA with 28 weeks of treatment with FASENRA (n=73) or placebo (n=75) in which the incidence was more common in FASENRA than placebo include headache (8.2% compared to 5.3%, respectively) and pyrexia (2.7% compared to 1.3%, respectively) [see Clinical Studies (14.1) ] . The frequencies for the remaining adverse reactions with FASENRA were similar to placebo. Injection Site Reactions in Patients with Asthma In SIROCCO and CALIMA, the FASENRA 30 mg prefilled syringe was administered at the recommended dosage and injection site reactions (e.g., pain, erythema, pruritus, papule) occurred at a rate of 2.2% in patients treated with FASENRA compared with 1.9% in patients treated with placebo. Pediatric Patients 6 to 11 Years of Age with Asthma The safety data for FASENRA is based on a 48-week, open-label, parallel group, pharmacokinetic and pharmacodynamic trial (TATE) of 28 pediatric patients aged 6 to 11 years with severe asthma, and with an eosinophilic phenotype [see Use in Specific Populations (8.4) and Clinical Pharmacology (12.2 , 12.3) ] . Patients received subcutaneous dose of 10 mg (for those weighing less than 35 kg) or 30 mg (for those weighing 35 kg or more) of FASENRA administered every 4 weeks for the first 3 doses, then every 8 weeks thereafter [see Dosage and Administration (2.1) ] . No new safety signals were observed in these patients. Adult Patients with EGPA The safety of FASENRA is based on 70 adult patients who received at least 1 dose of FASENRA 30 mg administered subcutaneously every 4 weeks in an active-controlled study …

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Risk Summary The data on pregnancy exposure from the clinical trials are insufficient to inform on drug-associated risk. Monoclonal antibodies such as benralizumab are transported across the placenta during the third trimester of pregnancy; therefore, potential effects on a fetus are likely to be greater during the third trimester of pregnancy. In a prenatal and postnatal development study conducted in cynomolgus monkeys, there was no evidence of fetal harm with IV administration of benralizumab throughout pregnancy at doses that produced exposures up to approximately 310 times the exposure at the maximum recommended human dose (MRHD) of 30 mg subcutaneously (see Data) . In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk In women with poorly or moderately controlled asthma, evidence demonstrates that there is an increased risk of preeclampsia in the mother and prematurity, low birth weight, and small for gestational age in the neonate. The level of asthma control should be closely monitored in pregnant women and treatment adjusted as necessary to maintain optimal control. Data Animal Data In a prenatal and postnatal development study, pregnant cynomolgus monkeys received benralizumab from beginning on GD20 to GD22 (dependent on pregnancy determination), on GD35, once every 14 days thereafter throughout the gestation period and 1-month postpartum (maximum 14 doses) at doses that produced exposures up to approximately 310 times that achieved with the MRHD (on an AUC basis with maternal IV doses up to 30 mg/kg once every 2 weeks). Benralizumab did not elicit adverse effects on fetal or neonatal growth (including immune function) up to 6.5 months after birth. There was no evidence of treatment-related external, visceral, or skeletal malformations. Benralizumab was not teratogenic in cynomolgus monkeys. Benralizumab crossed the placenta in cynomolgus monkeys. Benralizumab concentrations were approximately equal in mothers and infants on postpartum day 7, but were lower in infants at later time points. Eosinophil counts were suppressed in infant monkeys with gradual recovery by 6 months postpartum; however, recovery of eosinophil counts was not observed for one infant monkey during this period. 8.2 Lactation Risk Summary There is no information regarding the presence of benralizumab in human or animal milk, and the effects of benralizumab on the breast fed infant and on milk production are not known. However, benralizumab is a humanized monoclonal antibody (IgG1/κ-class), and immunoglobulin G (IgG) is present in human milk in small amounts. If benralizumab is transferred into human milk, the effects of local exposure in the gastrointestinal tract and potential limited systemic exposure in the infant to benralizumab are unknown. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for benralizumab and any potential adverse effects on the breast-fed child from benralizumab or from the underlying maternal condition. 8.4 Pediatric Use Asthma The safety and effectiveness of FASENRA for add-on maintenance treatment of patients with severe asthma and with an eosinophilic phenotype have been established in pediatric patients 6 years and older. Use of FASENRA for this indication is supported by evidence from the following: Pediatric Patients 12 to 17 Years of Age Use of FASENRA in pediatric patients 12 to 17 years of age with severe asthma and with an eosinophilic phenotype is supported by evidence from SIROCCO (n=53) and CALIMA (n=55) that enrolled 108 pediatric patients aged 12 to 17 years (mean age 14 years, 42% female, White 82%, Asian 2%, Black or African American 4%) with asthma. Of these patients, 46 received placebo, 40 received …

12.1 Mechanism of Action Benralizumab is a humanized afucosylated, monoclonal antibody (IgG1, kappa) that directly binds to the alpha subunit of the human interleukin-5 receptor (IL-5Rα) with a dissociation constant of 11 pM. The IL-5 receptor is expressed on the surface of eosinophils and basophils. In an in vitro setting, the absence of fucose in the Fc domain of benralizumab facilitates binding (45.5 nM) to FcɣRIII receptors on immune effector cells, such as natural killer (NK) cells, leading to apoptosis of eosinophils and basophils through antibody-dependent cell-mediated cytotoxicity (ADCC). Inflammation is an important component in the pathogenesis of asthma, EGPA, and HES. Multiple cell types (e.g., mast cells, eosinophils, neutrophils, macrophages, lymphocytes) and mediators (e.g., histamine, eicosanoids, leukotrienes, cytokines) are involved in inflammation. Benralizumab, by binding to the IL-5Rα chain, reduces eosinophils through ADCC; however, the mechanism of benralizumab action in asthma, EGPA, and HES has not been definitively established.

11 DESCRIPTION Benralizumab is a humanized monoclonal antibody (IgG1/κ-class) selective for interleukin-5 receptor alpha subunit (IL-5Rα). Benralizumab is produced in Chinese hamster ovary cells by recombinant DNA technology. Benralizumab has a molecular weight of approximately 150 kDa. FASENRA (benralizumab) injection is a sterile, preservative-free, clear to opalescent, colorless to slightly yellow solution for subcutaneous injection. Since benralizumab is a protein, a few translucent or white to off-white particles may be present in the solution. Each 10 mg single-dose prefilled syringe delivers 0.5 mL containing 10 mg benralizumab, L-histidine (0.7 mg); L-histidine hydrochloride monohydrate (1.2 mg); polysorbate 20 (0.03 mg); α,α‐trehalose dihydrate (47 mg); and Water for Injection, USP, at pH of 5.5 – 6.5. The single-dose prefilled syringe contains a 1 mL glass syringe with a staked 29-gauge 1⁄2 inch stainless steel needle. Each 30 mg single-dose prefilled syringe or single-dose autoinjector delivers 1 mL containing 30 mg benralizumab, L-histidine (1.4 mg); L-histidine hydrochloride monohydrate (2.3 mg); polysorbate 20 (0.06 mg); α,α‐trehalose dihydrate (95 mg); and Water for Injection, USP, at pH of 5.5 – 6.5. The single-dose prefilled syringe or single-dose autoinjector contains a 1 mL glass syringe with a staked 29-gauge 1⁄2 inch stainless steel needle.

10 OVERDOSAGE There is no specific treatment for an overdosage with benralizumab. If overdose occurs, the patient should be treated supportively with appropriate monitoring as necessary. Consider contacting the Poison Help line (1-800-222-1222) or a medical toxicologist for additional overdose management recommendations.

16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied FASENRA (benralizumab) injection is a sterile, preservative-free, clear to opalescent, colorless to slightly yellow solution and may contain a few translucent or white to off-white particles, for subcutaneous injection supplied as a single-dose prefilled syringe or single-dose autoinjector. The prefilled syringe (including stopper and cap) and autoinjector are not made with natural rubber latex. FASENRA is available as: Single-Dose Prefilled Syringe • Carton contains one 10 mg/0.5 mL single-dose prefilled syringe with a gray plunger rod: NDC 0310-1745-01 • Carton contains one 30 mg/mL single-dose prefilled syringe with a blue plunger rod: NDC 0310-1730-30 Single-Dose Autoinjector FASENRA PEN • Carton contains one 30 mg/mL single-dose autoinjector: NDC 0310-1830-30 Storage and Handling Store refrigerated at 36°F to 46°F (2°C to 8°C) in the original carton to protect from light. If needed, the prefilled syringe and autoinjector may be stored at room temperature up to 77°F (25°C) for a maximum of 14 days in the original carton to protect from light. Once removed from the refrigerator and brought to room temperature (up to 77°F [25°C]), the prefilled syringe and autoinjector must be used within 14 days or discarded. Do not freeze. Do not shake. Do not expose to heat.