Adbry

1 INDICATIONS AND USAGE ADBRY is indicated for the treatment of moderate-to-severe atopic dermatitis in adults and pediatric patients 12 years of age and older whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable. ADBRY can be used with or without topical corticosteroids. ADBRY is an interleukin-13 antagonist indicated for the treatment of moderate-to-severe atopic dermatitis in adults and pediatric patients 12 years of age and older whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable. ADBRY can be used with or without topical corticosteroids. ( 1 )

2 DOSAGE AND ADMINISTRATION Prior to ADBRY initiation, complete all age appropriate vaccinations as recommended by current immunization guidelines ( 2.1 ) Administer ADBRY by subcutaneous injection. ( 2.2 ) In pediatric patients 12 years of age and older, it is recommended that ADBRY be given by or under supervision of an adult. ( 2.2 ) The recommended dosage of ADBRY ( 2.3 ) Dosage in Adults Initial Loading Dose Subsequent Dosage Prefilled syringe 600 mg (four 150 mg injections) 300 mg (two 150 mg injections) every other week Autoinjector 600 mg (two 300 mg injections) 300 mg (one 300 mg injection) every other week Dosage in Pediatric Patients 12 Years of Age and Older Initial Loading Dose Subsequent Dosage Prefilled syringe 300 mg (two 150 mg injections) 150 mg (one 150 mg injection) every other week A dosage of 300 mg every 4 weeks may be considered for adult patients below 100 kg who achieve clear or almost clear skin after 16 weeks of treatment. ( 2.3 ) 2.1 Vaccination Prior to Treatment Complete all age-appropriate vaccinations as recommended by current immunization guidelines prior to initiating treatment with ADBRY [see Warnings and Precautions (5.4) ] . 2.2 Important Administration Instructions ADBRY is administered by subcutaneous injection. ADBRY is intended for use under the guidance of a healthcare provider. Provide proper training to patients and/or caregivers on the preparation and administration of ADBRY prior to use according to the "Instructions for Use" [see Instructions for Use ] . Use of the Autoinjector The ADBRY autoinjector is for use in adults only. A caregiver or adult patient may inject ADBRY using the autoinjector. Use of the Prefilled Syringe The ADBRY prefilled syringe is for use in adults and pediatric patients 12 years of age and older. A caregiver or patient 12 years of age and older may inject ADBRY using the prefilled syringe. In pediatric patients 12 years of age and older, administer ADBRY under the supervision of an adult. Administration Instructions Administer subcutaneous injection into the thigh or abdomen, except for the 2 inches (5 cm) around the navel. The upper arm can also be used if a caregiver administers the injection. DO NOT inject ADBRY into skin that is tender, damaged, bruised, or scarred. For adults taking the initial loading dose of 600 mg, administer each of the injections (four ADBRY 150 mg injections using prefilled syringes or two ADBRY 300 mg injections using autoinjectors) at different injection sites within the same body area. For the subsequent 300 mg doses using the prefilled syringe , administer the two ADBRY 150 mg injections at different injection sites within the same body area, rotating the body area with each subsequent set of injections. For the subsequent 300 mg doses using the autoinjector , administer one ADBRY 300 mg injection, rotating the body area with each subsequent injection For pediatric patients 12 years of age and older taking the initial loading dose of 300 mg, use prefilled syringes to administer the two ADBRY 150 mg injections at different injection sites within the same body area. For the subsequent 150 mg doses, use a prefilled syringe to administer one ADBRY 150 mg injection, rotating the body area with each subsequent injection. The ADBRY "Instructions for Use" contains more detailed instructions on the preparation and administration of ADBRY [see Instructions for Use ] . 2.3 Recommended Dosage Dosage in Adults The recommended dosage for adults is: Initial Loading Dose Subsequent Dosage Prefilled syringe 600 mg (four 150 mg injections) 300 mg (two 150 mg injections) every other week Autoinjector 600 mg (two 300 mg injections) 300 mg (one 300 mg injection) every other week After 16 weeks of treatment, for adult patients with body weight below 100 kg who achieve clear or almost clear skin, a dosage of 300 mg every 4 weeks may be considered. Dosage in Pediatric Patients 12 Years of Age and Older The recommended dosage for pediatric patients …

3 DOSAGE FORMS AND STRENGTHS ADBRY is a clear to opalescent, colorless to pale yellow solution available as: Injection: 150 mg/mL solution in a single-dose prefilled syringe with needle guard Injection: 300 mg/2 mL solution in a single-dose autoinjector Injection: 150 mg/mL solution in a single-dose prefilled syringe with needle guard. ( 3 ) 300 mg/2 mL solution in a single-dose autoinjector ( 3 )

4 CONTRAINDICATIONS ADBRY is contraindicated in patients who have known hypersensitivity to tralokinumab-ldrm or any excipients in ADBRY [see Warnings and Precautions (5.1) ] . Known hypersensitivity to tralokinumab-ldrm or any excipients in ADBRY. ( 4 )

6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail elsewhere in the labeling: Hypersensitivity [see Warnings and Precautions (5.1) ] Conjunctivitis and Keratitis [see Warnings and Precautions (5.2) ] Most common adverse reactions (incidence ≥ 1%) are upper respiratory tract infections, conjunctivitis, injection site reactions, and eosinophilia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact LEO Pharma Inc. at 1-877-494-4536 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 from Clinical Trials in Adults The safety of ADBRY was evaluated in a pool of 5 randomized, double-blind, placebo-controlled trials in subjects with moderate-to-severe atopic dermatitis including three phase 3 Eczema Tralokinumab trials (ECZTRA 1, ECZTRA 2, and ECZTRA 3), a dose-finding trial, and a vaccine response trial. The safety population had a mean age of 37 years; 43% of subjects were female, 67% were White, 21% were Asian, and 9% were Black. In terms of co-morbid conditions, 39% of the subjects had asthma, 49% had hay fever, 36% had food allergy, and 21% had allergic conjunctivitis at baseline. In these 5 atopic dermatitis trials, 1964 subjects were treated with subcutaneous injections of ADBRY, with or without concomitant topical corticosteroids (TCS). A total of 807 subjects were treated with ADBRY for at least 1 year. ECZTRA 1 and ECZTRA 2 compared the safety of ADBRY monotherapy to placebo through Week 52. ECZTRA 3 compared the safety of ADBRY + TCS to placebo + TCS through Week 32. Weeks 0 to 16 (ECZTRA 1, ECZTRA 2, and ECZTRA 3): Table 1 summarizes the adverse reactions identified in the pool of 3 trials (ECZTRA 1, ECZTRA 2, and ECZTRA 3) and that occurred at a rate of at least 1% in the ADBRY 300 mg every other week monotherapy group, and in the ADBRY 300 mg every other week + TCS trial, all at a higher rate than placebo during the first 16 weeks of treatment. Table 1: Adverse Reactions Occurring in ≥1% of the ADBRY Monotherapy Group or the ADBRY + TCS Group in the Atopic Dermatitis Trials through Week 16 Adverse Reaction ADBRY Monotherapy Pooled analysis of ECZTRA 1 and ECZTRA 2. ADBRY + TCS Analysis of ECZTRA 3 where subjects were on background TCS therapy. ADBRY 300 mg Q2W ADBRY 600 mg at Week 0, followed by 300 mg every other week. PLACEBO ADBRY 300 mg Q2W + TCS PLACEBO + TCS N=1180 n (%) N=388 n (%) N=243 n (%) N=123 n (%) Upper respiratory tract infections Upper respiratory tract infections cluster includes upper respiratory tract infection, viral upper respiratory tract infection, pharyngitis, and nasopharyngitis; mainly reported as common cold. 281 (23.8) 79 (20.4) 73 (30.0) 19 (15.4) Conjunctivitis Conjunctivitis cluster includes conjunctivitis and allergic conjunctivitis. 88 (7.5) 12 (3.1) 33 (13.6) 6 (4.9) Injection site reactions Injection site reactions cluster includes pain, erythema, and swelling. 87 (7.4) 16 (4.1) 27 (11.1) 1 (0.8) Eosinophilia Eosinophilia cluster includes eosinophilia and eosinophil count increased. 17 (1.4) 2 (0.5) 3 (1.2) 0 In the monotherapy trials (ECZTRA 1 and ECZTRA 2) through Week 16, the proportion of subjects who discontinued treatment due to adverse reactions was 0.7% in the ADBRY 300 mg every other week group and 0% of the placebo group. In the concomitant TCS trial (ECZTRA 3) through Week 16, the proportion of subjects who discontinued treatment due to adverse reactions was 0.8% in the ADBRY 300 mg every other week +TCS group and 0% of the placebo + TCS group. The most common adverse reactions leading to discontinuation in the ADBRY group compared to the placebo group were injection site reaction (0.3% v. 0) and eosinophilia (0.3% v. 0) in ECZTRA 1 …

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 ADBRY during pregnancy. Healthcare providers are encouraged to register pregnant patients, or pregnant women may enroll themselves in the registry by calling 1-877-311-8972 or visiting https://mothertobaby.org/ongoing-study/adbry-tralokinumab/. Risk Summary There are limited data from the use of ADBRY in pregnant women to inform a drug-associated risk of adverse developmental outcomes. Monoclonal antibodies are actively transported across the placenta (see Clinical Considerations ) . In an enhanced pre-and post-natal developmental study, no adverse developmental effects were observed in offspring born to pregnant monkeys after intravenous administration of tralokinumab-ldrm during organogenesis through parturition at doses up to 10 times the maximum recommended human dose (MRHD). The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss or other adverse outcomes. 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 Fetal/Neonatal Adverse Reactions Transport of endogenous IgG antibodies across the placenta increases as pregnancy progresses and peaks during the third trimester. Therefore, ADBRY may be present in infants exposed in utero . The potential clinical impact of tralokinumab-ldrm exposure in infants exposed in utero should be considered. Data Animal Data In a pre- and post-natal development study, intravenous doses up to 100 mg/kg tralokinumab-ldrm were administered to pregnant cynomolgus monkeys once every week from gestation day 20 to parturition. No maternal or developmental toxicity was observed at doses up to 100 mg/kg/week (10 times the MRHD on a mg/kg basis of 10 mg/kg/week). In an enhanced pre- and post-natal development study, intravenous doses up to 100 mg/kg tralokinumab-ldrm (10 times the MRHD on a mg/kg basis of 10 mg/kg/week) were administered to pregnant cynomolgus monkeys once every week from the beginning of organogenesis to parturition. No treatment-related adverse effects on embryofetal toxicity or malformations, or on morphological, functional, or immunological development were observed in the infants from birth through 6 months of age. 8.2 Lactation Risk Summary There are no data on the presence of tralokinumab-ldrm in human milk, the effects on the breastfed infant, or the effects on milk production. Maternal IgG is present in breast milk. The effects of local gastrointestinal exposure and limited systemic exposure to ADBRY on the breastfed infant are unknown. The development and health benefits of breastfeeding should be considered along with the mother's clinical need for ADBRY and any potential adverse effects on the breastfed child from ADBRY or from the underlying maternal condition. 8.4 Pediatric Use The safety and effectiveness of ADBRY have been established for the treatment of moderate-to-severe atopic dermatitis in pediatric patients 12 years of age and older whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable. Use of ADBRY in this age group is supported by a multicenter, randomized, double-blind, placebo-controlled trial (ECZTRA 6) in 289 subjects 12 to 17 years of age with moderate-to-severe atopic dermatitis. Of the 289 subjects, 195 were treated with ADBRY and 94 were treated with matching placebo. The safety and effectiveness were consistent between subjects 12 to 17 years of age and adult subjects [see Adverse Reactions (6.1) and Clinical Studies (14) ] . Safety and effectiveness of ADBRY have not been established in pediatric patients younger than 12 years of age. 8.5 Geriatric Use Of the 1605 subjects e …

12.1 Mechanism of Action Tralokinumab-ldrm is a human IgG4 monoclonal antibody that specifically binds to human interleukin-13 (IL-13) and inhibits its interaction with the IL-13 receptor α1 and α2 subunits (IL-13Rα1 and IL-13Rα2). IL-13 is a naturally occurring cytokine of the Type 2 immune response. Tralokinumab-ldrm inhibits the bioactivity of IL-13 by blocking IL-13 interaction with IL-13Rα1/IL-4Rα receptor complex. Tralokinumab-ldrm inhibits IL-13-induced responses including the release of proinflammatory cytokines, chemokines and IgE.

11 DESCRIPTION Tralokinumab-ldrm, an interleukin-13 antagonist, is a human IgG4 monoclonal antibody. Tralokinumab-ldrm is produced in mouse myeloma cells by recombinant DNA technology, consists of 1326 amino acids, and has a molecular weight of approximately 147 kilodaltons. ADBRY (tralokinumab-ldrm) injection is a sterile, preservative-free, clear to opalescent, colorless to pale yellow solution for subcutaneous use supplied as either a single-dose prefilled syringe with needle guard in a siliconized Type-1 clear glass syringe or a single-dose autoinjector with a siliconized Type-1 clear glass syringe inside. None of the components of the prefilled syringe, autoinjector or the needle guard are made with natural rubber latex. Each prefilled syringe delivers 150 mg tralokinumab-ldrm in 1 mL and the inactive ingredients: acetic acid (0.3 mg), polysorbate 80 (0.1 mg), sodium acetate trihydrate (6 mg), sodium chloride (5 mg), and Water for Injection, at an approximate pH of 5.5. Each autoinjector delivers 300 mg tralokinumab-ldrm in 2 mL and the inactive ingredients: acetic acid (0.6 mg), polysorbate 80 (0.2 mg), sodium acetate trihydrate (12 mg), sodium chloride (10 mg), and Water for Injection, at an approximate pH of 5.5.

10 OVERDOSAGE There is no specific treatment for ADBRY overdose. In the event of overdosage, contact Poison Control (1-800-222-1222) for latest recommendations and monitor the patient for any signs or symptoms of adverse reactions and institute appropriate symptomatic treatment immediately.

16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied ADBRY (tralokinumab-ldrm) injection is a sterile, clear to opalescent, colorless to pale yellow solution, supplied in a single-dose prefilled syringe with a 27-gauge, 1⁄2 inch needle and a needle guard, or a single-dose autoinjector with a 27-gauge, 1⁄2 inch needle. Each prefilled syringe delivers 150 mg of ADBRY in 1 mL solution (NDC 50222-346-01). Each autoinjector delivers 300 mg of ADBRY in 2 mL solution (NDC 50222-350-00). ADBRY is available in pack sizes containing either 2 or 4 prefilled syringes with needle guard or 1 or 2 autoinjectors. 150 mg in a 1 mL prefilled syringe – Pack Size NDC # Two cartons (multipack) containing 4 prefilled syringes NDC 50222-346-04 One carton containing 2 prefilled syringes NDC 50222-346-02 300 mg in a 2 mL autoinjector – Pack Size NDC # One carton containing 2 autoinjectors NDC 50222-350-02 One carton containing 1 autoinjector NDC 50222-350-01 Storage and Handling ADBRY does not contain preservatives. Discard any unused portion. Store refrigerated at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light. If necessary, ADBRY may be kept at room temperature up to 30°C (86°F) for a maximum of 14 days in the original carton. Do not store above 30°C (86°F). Do not put ADBRY back in the refrigerator after reaching room temperature. If the carton needs to be removed permanently from refrigerator, the date of removal may be recorded on the outer carton in the space provided. After removal from the refrigerator, ADBRY must be used within 14 days or discarded. Do not expose ADBRY to heat or direct sunlight. Do not freeze. Do not shake.