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…

5 WARNINGS AND PRECAUTIONS Hypersensitivity: Hypersensitivity reactions, including anaphylaxis, and angioedema have occurred after administration of ADBRY. Discontinue ADBRY in the event of a hypersensitivity reaction. ( 5.1 ) Conjunctivitis and Keratitis: Patients should report new onset or worsening eye symptoms to their healthcare provider. ( 5.2 ) Parasitic (Helminth) Infections: Treat patients with pre-existing helminth infections before initiating treatment with ADBRY. If patients become infected while receiving ADBRY and do not respond to anti-helminth treatment, discontinue treatment with ADBRY until the infection resolves. ( 5.3 ) Risk of Infection with Live Vaccines: Avoid use of live vaccines. ( 5.4 ) 5.1 Hypersensitivity Hypersensitivity reactions including anaphylaxis and angioedema have been reported with use of ADBRY. If a serious hypersensitivity reaction occurs, discontinue ADBRY immediately and initiate appropriate therapy. 5.2 Conjunctivitis and Keratitis Conjunctivitis and keratitis occurred more frequently in atopic dermatitis subjects who received ADBRY. Conjunctivitis was the most frequently reported eye disorder. Most subjects with conjunctivitis or keratitis recovered or were recovering during the treatment period [see Adverse Reactions (6.1) ]. Advise patients to report new onset or worsening eye symptoms to their healthcare provider. 5.3 Parasitic (Helminth) Infections Patients with known helminth infections were excluded from participation in clinical studies. It is unknown if ADBRY will influence the immune response against helminth infections by inhibiting IL-13 signaling. Treat patients with pre-existing helminth infections before initiating treatment with ADBRY. If patients become infected while receiving ADBRY and do not respond to antihelminth treatment, discontinue treatment with ADBRY until the infection resolves. 5.4 Risk of Infection with Live Vaccines ADBRY may alter a patient's immunity and increase the risk of infection following administration of live vaccines. Prior to initiating therapy with ADBRY, complete all age-appropriate vaccinations according to current immunization guidelines. Avoid use of live vaccines during treatment with ADBRY. Limited data are available regarding coadministration of ADBRY with non-live vaccines [see Clinical Pharmacology (12.2) ].

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 )

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.

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…