SAPHNELO

Dosage and Administration ( 2 ) 04/2026

1 INDICATIONS AND USAGE SAPHNELO is indicated for the treatment of adult patients with moderate to severe systemic lupus erythematosus (SLE), who are receiving standard therapy. Limitations of Use The efficacy of SAPHNELO has not been evaluated in patients with severe active lupus nephritis or severe active central nervous system lupus. Use of SAPHNELO is not recommended in these situations. SAPHNELO is a type I interferon (IFN) receptor antagonist indicated for the treatment of adult patients with moderate to severe systemic lupus erythematosus (SLE), who are receiving standard therapy. ( 1 ) Limitations of Use: The efficacy of SAPHNELO has not been evaluated in patients with severe active lupus nephritis or severe active central nervous system lupus. Use of SAPHNELO is not recommended in these situations. ( 1 )

2 DOSAGE AND ADMINISTRATION • The recommended intravenous dosage is 300 mg every 4 weeks. ( 2.2 ) • The recommended subcutaneous dosage is 120 mg once every week. ( 2.2 ) • See Full Prescribing Information for complete preparation and administration information. ( 2.3 , 2.4 ) 2.1 Important Administration Information SAPHNELO is intended for use under the guidance of a healthcare provider and may be administered as an intravenous infusion or as a subcutaneous injection. SAPHNELO vials are for intravenous use only and must be diluted prior to intravenous administration [see Dosage and Administration (2.3) ] . SAPHNELO prefilled syringe and autoinjector (SAPHNELO PEN) are for subcutaneous use only [see Dosage and Administration (2.4) ] . 2.2 Recommended Dosage The recommended dosage of SAPHNELO is: • 300 mg, administered as an intravenous infusion over a 30‐minute period every 4 weeks; or • 120 mg, administered as a subcutaneous injection once every week. Missed Dose If a planned intravenous infusion is missed, administer SAPHNELO as soon as possible. Maintain a minimum interval of 14 days between infusions. If a planned subcutaneous dose is missed, instruct the patient to administer SAPHNELO as soon as they remember. Thereafter, instruct the patient to start a new weekly schedule from the day the missed dose was administered or resume dosing on their usual day of administration, providing a minimum interval of 3 days between subcutaneous injections. 2.3 Intravenous Preparation and Administration Instructions SAPHNELO is supplied as a single-dose vial. Prepare the diluted infusion solution using aseptic technique, by the following procedure: 1. Visually inspect the vial for particulate matter and discoloration. SAPHNELO is a clear to opalescent, colorless to slightly yellow, solution. Discard the vial if the solution is cloudy, discolored or visible particles are observed. Do not shake the vial. 2. Withdraw and discard 2 mL of solution from a 50 mL or 100 mL 0.9% Sodium Chloride Injection, USP infusion bag. 3. Withdraw 2 mL of solution from the vial of SAPHNELO and add it to the infusion bag. Mix the solution by gentle inversion. Do not shake. 4. Each vial is intended for one time use only. Discard any unused portion remaining in the vial. 5. Administer the infusion solution immediately after preparation. 6. If the infusion solution is not administered immediately, store the diluted solution of SAPHNELO at room temperature 59°F to 77°F (15°C to 25°C) for up to 4 hours, or refrigerated 36°F to 46°F (2°C to 8°C) for up to 24 hours. Do not freeze. Protect from light. If refrigerated, allow the diluted SAPHNELO solution to reach room temperature prior to administration. 7. Administer the infusion solution intravenously over a 30-minute period through an infusion line containing a sterile, low-protein binding 0.2 to 15 micron in-line or add-on filter. 8. To ensure the complete dose of SAPHNELO has been administered, flush the entire infusion line with 25 mL of 0.9% Sodium Chloride Injection, USP at the end of the infusion. 9. Do not co-administer other medicinal products through the same infusion line. 10. Dispose of any unused medicinal product or waste material in accordance with local requirements . 2.4 Subcutaneous Preparation and Administration Instructions The SAPHNELO prefilled syringe and autoinjector (SAPHNELO PEN) are for subcutaneous use. 1. Comprehensive instructions for subcutaneous administration of SAPHNELO using the prefilled syringe or autoinjector are provided in the ‘Instructions for Use’. 2. Patients/caregivers may administer SAPHNELO prefilled syringe/SAPHNELO PEN after proper training in the subcutaneous injection technique and after the healthcare provider determines it is appropriate. 3. Prior to administration, remove SAPHNELO from the refrigerator and allow it to come to room temperature for 60 minutes. 4. Visually inspect SAPHNELO for particulate matter and discoloration prior to administration. SAPHNELO is …

3 DOSAGE FORMS AND STRENGTHS Intravenous Infusion • Injection: 300 mg/2 mL (150 mg/mL) as a clear to opalescent, colorless to slightly yellow solution in a single-dose vial. Subcutaneous Injection • Injection: 120 mg/0.8 mL as a clear to opalescent, colorless to slightly yellow solution in a single-dose prefilled syringe or single-dose autoinjector (SAPHNELO PEN). Intravenous Infusion: • Injection: 300 mg/2 mL (150 mg/mL) in a single-dose vial. ( 3 ) Subcutaneous Injection: • Injection: 120 mg/0.8 mL in a single-dose prefilled syringe or single-dose autoinjector (SAPHNELO PEN). ( 3 )

4 CONTRAINDICATIONS SAPHNELO is contraindicated in patients with a history of anaphylaxis with anifrolumab-fnia [see Warnings and Precautions (5.2) ] . SAPHNELO is contraindicated in patients with a history of anaphylaxis with anifrolumab-fnia. ( 4 )

6 ADVERSE REACTIONS The following clinically significant adverse reactions are also discussed elsewhere in the labeling: • Serious Infections [see Warnings and Precautions (5.1) ] • Hypersensitivity Reactions Including Anaphylaxis [see Warnings and Precautions (5.2) ] • Malignancy [see Warnings and Precautions (5.3) ] Most common adverse drug reactions (incidence ≥5%) are nasopharyngitis, upper respiratory tract infections, bronchitis, infusion related reactions, herpes zoster and cough. ( 6 ) 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. Adverse Reactions with Intravenous Administration The safety of SAPHNELO was assessed in adult patients with moderate to severe SLE who received SAPHNELO 300 mg by intravenous infusion every 4 weeks (N=459) for 52 weeks, compared to placebo (N=466) in controlled clinical trials (Trials 1, 2 and 3) [see Clinical Studies (14.1) ]. The population studied had a mean age of 41 years (range: 18 to 69), of which 93% were female, 60% White, 13% Black/African American, and 10% Asian. In the controlled-clinical trials, adverse reactions, irrespective of causality, were reported in 87% of patients receiving SAPHNELO and 79% of patients receiving placebo. Adverse reactions that occurred at greater than or equal to 2% incidence are shown in Table 1. Table 1 Adverse Reactions Occurring in ≥2% of Adults with Moderate to Severe SLE Treated with Intravenous SAPHNELO for 52 weeks in Trials 1, 2 and 3 Adverse Reaction SAPHNELO (N=459) % Placebo (N=466) % Upper respiratory tract infection Upper respiratory tract infections (including Upper respiratory tract infections, Nasopharyngitis, Pharyngitis) 34 23 Bronchitis Bronchitis (including Bronchitis, Bronchitis viral, Tracheobronchitis) 11 5.2 Infusion‐related reactions 9.4 7.1 Herpes Zoster 6.1 1.3 Cough 5.0 3.2 Respiratory tract infection Respiratory tract infection (including Respiratory tract infection, Respiratory tract infection viral, Respiratory tract infection bacterial) 3.3 1.5 Hypersensitivity 2.8 0.6 All patients received standard therapy. Long-term Safety Patients who completed Trials 2 and 3 (Phase III feeder trials) were eligible to continue on treatment in a randomized, double-blind, placebo-controlled long-term extension (LTE) trial, for an additional 3 years. The long-term safety of SAPHNELO was assessed in 257 patients who received SAPHNELO 300 mg every 4 weeks and 112 patients who received placebo in both a feeder trial and the LTE. Of these, 177 patients who received SAPHNELO (68.9%) and 52 patients who received placebo (46.4%) completed a total of 4 years on treatment. The overall long-term safety profile of SAPHNELO was consistent with Trials 1, 2 and 3. Specific Adverse Reactions Infections: In the 52‐week controlled-clinical trials, infections were reported in a greater proportion of patients while on treatment with SAPHNELO compared to placebo (69.7% versus 55.4%, respectively). Herpes Zoster: In the 52‐week controlled-clinical trials, the incidence of herpes zoster in patients while on treatment with SAPHNELO was 6.1% and 1.3% in patients on placebo. Cases with multidermatomal involvement and disseminated presentation have been reported. Of the 28 SAPHNELO-treated patients with herpes zoster, 2 experienced disseminated disease requiring hospitalization compared to none among placebo-treated patients. Hypersensitivity Reactions Including Anaphylaxis: During the SLE intravenous development program, there was one report of an anaphylactic reaction in a patient who received SAPHNELO 150 mg, and 4 reports of angioedema after 300 mg. In general, the hypersensitivity reaction …

7 DRUG INTERACTIONS No formal drug interaction trials have been conducted.

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to SAPHNELO during pregnancy. For more information about the registry or to report a pregnancy while on SAPHNELO, healthcare providers should contact AstraZeneca at 1‐877‐693‐9268 or https://anifrolumabpregnancyandbreastfeedingstudy.us/ . Risk Summary The limited human data with SAPHNELO use in pregnant women are insufficient to inform on drug‐associated risk for major birth defects, miscarriage, or adverse maternal or fetal outcome. Monoclonal IgG antibodies are known to be actively transported across the placenta as pregnancy progresses; therefore, anifrolumab‐fnia exposure to the fetus may be greater during the third trimester of pregnancy. In an enhanced pre- and post-natal development study with pregnant cynomolgus monkeys that received intravenous administration of anifrolumab-fnia, there was no evidence of embryotoxicity or fetal malformations with exposures up to approximately 28‐times the exposure at the maximum recommended human dose (MRHD) on an Area Under Curve (AUC) basis (see Data ) . All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. 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 : Pregnant women with SLE are at increased risk of adverse pregnancy outcomes, including worsening of the underlying disease, premature birth, miscarriage, and intrauterine growth restriction. Maternal lupus nephritis increases the risk of hypertension and preeclampsia/eclampsia. Passage of maternal autoantibodies across the placenta may result in adverse neonatal outcomes, including neonatal lupus and congenital heart block. Data Animal Data : In an enhanced pre- and post-natal development study, pregnant cynomolgus monkeys received anifrolumab-fnia at intravenous doses of 30 or 60 mg/kg once every 2 weeks from confirmation of pregnancy at Gestation Day 20, throughout the gestation period, and continuing until 1‐month post-partum (approximately Lactation Day 28). There was no evidence of anifrolumab-fnia related maternal toxicity, embryo-fetal toxicity, or post-natal developmental effects. No anifrolumab-fnia related effect on T-cell-dependent antibody response in the infants was noted up to Day 180 after birth. The no observed adverse effect level (NOAEL) for maternal and developmental toxicity was identified as 60 mg/kg (approximately 28‐times the MRHD on an AUC basis). In the infants, mean serum concentrations of anifrolumab‐fnia on Day 30 after birth increased with dose and were approximately 4.2% to 9.7% of the respective maternal concentrations. The anifrolumab-fnia concentrations in the infant serum were up to approximately 22‐times the concentrations in the maternal milk, suggesting that anifrolumab-fnia had transferred via the placenta. 8.2 Lactation Risk Summary No data are available regarding the presence of SAPHNELO in human milk, the effects on the breastfed child, or the effects on milk production. Anifrolumab-fnia was detected in the milk of female cynomolgus monkeys administered anifrolumab-fnia. Due to species-species differences in lactation physiology, animal data may not reliably predict drug levels in humans. Maternal IgG is known to be present in human milk. If anifrolumab-fnia is transferred into human milk, the effects of local gastrointestinal exposure and limited systemic exposure in the breastfed infant to anifrolumab-fnia are unknown. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for SAPHNELO and any potential adverse effects on the …

12.1 Mechanism of Action Anifrolumab-fnia is a human IgG1κ monoclonal antibody that binds to subunit 1 of the type I interferon receptor (IFNAR) with high specificity and affinity. This binding inhibits type I IFN signaling, thereby blocking the biologic activity of type I IFNs. Anifrolumab-fnia also induces the internalization of IFNAR1, thereby reducing the levels of cell surface IFNAR1 available for receptor assembly. Blockade of receptor mediated type I IFN signaling inhibits IFN responsive gene expression as well as downstream inflammatory and immunological processes. Inhibition of type I IFN blocks plasma cell differentiation and normalizes peripheral T-cell subsets. Type I IFNs play a role in the pathogenesis of SLE. Approximately 60-80% of adult patients with active SLE express elevated levels of type I IFN inducible genes.

11 DESCRIPTION Anifrolumab-fnia is a type I interferon (IFN) receptor antagonist, immunoglobulin G1 kappa (IgG1κ) monoclonal antibody that is produced in mouse myeloma cells (NS0) by recombinant DNA technology. The molecular weight is approximately 148 kDa. Intravenous Infusion SAPHNELO (anifrolumab-fnia) injection is a sterile, preservative‐free, clear to opalescent, colorless to slightly yellow, solution in a single-dose vial for intravenous use. Each 2 mL single-dose vial contains 300 mg (150 mg/mL) of anifrolumab-fnia, L-histidine (3 mg), L-histidine hydrochloride monohydrate (6 mg), L-lysine hydrochloride (18 mg), polysorbate 80 (1 mg), trehalose dihydrate (98 mg), and Water for Injection, USP. The pH is 5.9. Subcutaneous Injection SAPHNELO (anifrolumab-fnia) injection is a sterile, preservative-free, clear to opalescent, colorless to slightly yellow, solution in a prefilled syringe or autoinjector for subcutaneous injection. Each 0.8 mL single-dose prefilled syringe or autoinjector delivers 120 mg of anifrolumab-fnia, histidine (1 mg), L-histidine hydrochloride monohydrate (3 mg), lysine hydrochloride (7 mg), polysorbate 80 (0.4 mg), trehalose (36 mg), and Water for Injection, USP. The pH is 5.9.

16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied SAPHNELO (anifrolumab-fnia) injection is a sterile, preservative-free, clear to opalescent, colorless to slightly yellow solution in a single-dose vial for intravenous infusion or a prefilled syringe or autoinjector for subcutaneous injection. SAPHNELO is available as follows: Packaging Unit and Strength Pack Size and NDC 300 mg/2 mL (150 mg/mL) single-dose vial (NDC 0310-3040-00) One vial in a carton: NDC 0310-3040-00 120 mg/0.8 mL single-dose prefilled syringe (NDC 0310-3080-75) One syringe in a carton: NDC 0310-3080-02 120 mg/0.8 mL single-dose autoinjector (SAPHNELO PEN) (NDC 0310-3080-25) One autoinjector in a carton: NDC 0310-3080-01 The prefilled syringe (including needle cover) and autoinjector (including cap) are not made with natural rubber latex. Storage and Handling Store SAPHNELO in a refrigerator at 36°F to 46°F (2°C to 8°C) in the original carton to protect from light. • Do not freeze. Do not shake. Do not expose to heat. Do not use SAPHNELO past the expiration date. If needed, SAPHNELO prefilled syringe or autoinjector can be stored at room temperature 68°F to 77°F (20°C to 25°C) for up to 7 days in the original carton to protect from light. After the SAPHNELO prefilled syringe or autoinjector has reached room temperature, do not return to the refrigerator. Discard SAPHNELO prefilled syringe or autoinjector if not used within 7 days at room temperature storage.