ADVERSE REACTIONS SECTION.

6 ADVERSE REACTIONS. The following adverse reactions are described elsewhere in the labeling:Hypersensitivity [see Warnings and Precautions (5.1)] Conjunctivitis and Keratitis [see Warnings and Precautions (5.2)] Hypersensitivity [see Warnings and Precautions (5.1)] Conjunctivitis and Keratitis [see Warnings and Precautions (5.2)] Most common (>=1%) adverse reactions are conjunctivitis, injection site reactions, and herpes zoster. (6.1)To report SUSPECTED ADVERSE REACTIONS, contact Eli Lilly and Company at 1-800-LillyRx (1-800-545-5979) 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 and controlled conditions, adverse reaction rates observed in the clinical trials of drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.. Atopic DermatitisThe safety of EBGLYSS was evaluated across randomized, double-blind, placebo-controlled, multicenter trials in subjects with moderate-to-severe atopic dermatitis including phase trials (ADvocate 1, ADvocate 2, ADhere) and phase dose ranging trial (KGAF). In these trials, mean age was 37 years; 50% of subjects were male; 62% were White, 13% were Black, and 20% were Asian. In terms of co-morbid conditions, in the phase trials, 30% of the subjects had asthma, 50% had allergic rhinitis, 31% had food allergy, and 14% had allergic conjunctivitis at baseline.A total of 891 subjects were treated with EBGLYSS for at least year in the atopic dermatitis development program.ADvocate 1, ADvocate 2, and KGAF compared the safety of EBGLYSS monotherapy to placebo. ADhere compared the safety of EBGLYSS TCS to placebo TCS through 16 weeks. All subjects from the phase trials were allowed to enroll in the long-term extension study.. Weeks to 16Table summarizes the adverse reactions that occurred at rate of at least 1% in the EBGLYSS 250 mg every weeks monotherapy group, or in the EBGLYSS 250 mg every weeks TCS group, all at higher rate than placebo during the first 16 weeks of treatment.Table 1: Adverse Reactions Occurring in >=1% of the EBGLYSS Monotherapy Group or the EBGLYSS TCS Group in the Atopic Dermatitis Trials through Week 16a Integrated analysis of ADvocate 1, ADvocate 2, and the phase dose finding trial (KGAF)b Analysis of TCS concomitant therapy trial ADherec EBGLYSS 500 mg at Week and Week 2, followed by 250 mg every two weeksd Conjunctivitis cluster includes conjunctivitis, conjunctivitis allergic, and conjunctivitis bacteriale Injection Site Reactions cluster includes injection site-related: pain, erythema, reaction, discomfort, dermatitis, pruritus, swelling, and rashAdverse ReactionsEBGLYSS MonotherapyaEBGLYSS TCSbEBGLYSS250 mg Q2WcN 638n (%)PlaceboN 338n (%)EBGLYSS250 mg Q2Wc+ TCSN 145n (%)Placebo TCSN 66n (%)Conjunctivitisd 61 (10)10 (3)7 (5)0Injection Site Reactionse 16 (3)4 (1)4 (3)1 (2)Herpes Zoster3 (<1)02 (1)0In the monotherapy trials (ADvocate 1, ADvocate 2, and KGAF) through Week 16, the proportion of subjects who discontinued treatment due to adverse events was 2.4% in the EBGLYSS 250 mg every weeks group and 1.8% in the placebo group. In the TCS trial (ADhere) through Week 16, the proportion of subjects who discontinued treatment due to adverse events was 2.1% in the EBGLYSS 250 mg every weeks TCS group and 0% in the placebo TCS group. The most common adverse reactions leading to discontinuation of EBGLYSS compared to the placebo group were conjunctivitis and keratitis (0.6% vs. 0.3%), and injection site reactions (0.2% vs. 0) in the monotherapy trials; and conjunctivitis (0.7% vs. 0), and injection site reactions (0.7% vs. 0) in the TCS trial.. EosinophiliaIncreased post-baseline blood eosinophils were observed at higher frequency in EBGLYSS-treated subjects compared to placebo. During the first 16 weeks, eosinophilia (>5000 cells/mcL) was observed in 0.4% in the EBGLYSS-treated subjects and 0% in subjects receiving placebo. Blood eosinophil elevations were generally transient and did not result in discontinuation.. Safety Weeks 16 to 52Among those EBGLYSS-treated subjects who responded at Week 16 and who were re-randomized in the maintenance period of the monotherapy trials ADvocate and ADvocate 2, total of 113 and 118 subjects received EBGLYSS 250 mg every weeks or every weeks, respectively. The safety profile of EBGLYSS 250 mg every weeks was generally consistent with EBGLYSS every weeks during Weeks 16 to 52. The safety profile of EBGLYSS during maintenance treatment was generally consistent with the safety profile observed through Week 16.. Specific Adverse Drug Reactions. Conjunctivitis and KeratitisConjunctivitis was the most frequently reported eye disorder. Most cases of conjunctivitis and keratitis were mild or moderate in severity and recovered or resolved without treatment interruption or discontinuation.During the initial 16-week treatment period of the monotherapy trials, conjunctivitis, including allergic conjunctivitis, was reported by 61 subjects (10%) in the EBGLYSS 250 mg every weeks group and 10 subjects (3%) in the placebo group. In the TCS concomitant therapy trial, conjunctivitis was reported by subjects (5%) in the EBGLYSS 250 mg every weeks TCS group compared to 0% in the placebo TCS group. During the 16-week placebo-controlled induction period, 68 subjects reported 73 events of conjunctivitis. All events were nonserious and mild or moderate in severity. Conjunctivitis led to treatment discontinuation in subjects. The exposure adjusted incidence rate of conjunctivitis for subjects treated with EBGLYSS 250 mg every weeks was 30.6 events per 100 patient years through Week 16 (KGAF, ADvocate 1, ADvocate 2, ADhere).During the maintenance treatment period of the monotherapy trials (ADvocate and ADvocate 2) from 16 to 52 weeks, conjunctivitis, including allergic conjunctivitis, was reported by subjects (1.8%) in the EBGLYSS 250 mg every weeks group and 12 subjects (10.1%) in the EBGLYSS 250 mg every weeks group, compared to subjects (8.3%) in the placebo group. During the maintenance treatment period, 14 subjects treated with EBGLYSS reported 18 events of conjunctivitis. All events were mild or moderate in severity. Conjunctivitis led to treatment discontinuation in subjects in the EBGLYSS 250 mg every weeks group. The exposure adjusted incidence rate of conjunctivitis for subjects treated with EBGLYSS 250 mg every weeks was 18.3 events per 100 patient years and for those treated with EBGLYSS 250 mg every weeks was 20.6 events per 100 patient years through Week 52 (ADvocate 1, ADvocate 2, ADhere the long-term extension study).During the initial 16-week treatment period of the monotherapy trials, keratitis, including atopic and vernal keratoconjunctivitis, was reported by subjects (0.6%) in the EBGLYSS 250 mg every weeks group and subject (0.3%) in the placebo group. In the TCS concomitant therapy trial, vernal keratoconjunctivitis was reported by subject (0.7%) in the EBGLYSS 250 mg every weeks TCS group, compared to 0% in the placebo TCS group. All events were nonserious and mild or moderate in severity. Keratitis led to treatment discontinuation in subjects. The exposure adjusted incidence rate of keratitis for subjects treated with EBGLYSS 250 mg every weeks was 2.2 events per 100 patient years through Week 16 (KGAF, ADvocate 1, ADvocate 2, ADhere).During the maintenance treatment period of the monotherapy trials (ADvocate and ADvocate 2) from 16 to 52 weeks, atopic keratoconjunctivitis was reported by subject (0.8%) in the EBGLYSS 250 mg every weeks group, and vernal keratoconjunctivitis was reported by subject (0.9%) in the EBGLYSS 250 mg every weeks group, compared to 0% in the placebo group. One (0.9%) event of severe vernal keratoconjunctivitis in an EBGLYSS 250 mg every weeks subject led to treatment discontinuation. The exposure adjusted incidence rate of keratitis for subjects treated with EBGLYSS 250 mg every weeks was 1.0 event per 100 patient years and for those treated with EBGLYSS 250 mg every weeks was 0.7 events per 100 patient years through Week 52 (ADvocate 1, ADvocate 2, ADhere the long-term extension study).. Injection Site ReactionsInjection site reactions were reported by 3% of the EBGLYSS group and 1% of the placebo group in the first 16 weeks of the monotherapy trials. Incidence of injection site reactions declined with continued treatment. Most events were mild or moderate and recovered without treatment discontinuation.

CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY SECTION.

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility. Animal studies have not been conducted to evaluate the carcinogenic or mutagenic potential of lebrikizumab-lbkz.No effects on fertility parameters such as reproductive organs, reproductive hormones or menstrual cycle length were observed in sexually mature female cynomolgus monkeys that were administered intravenous doses of lebrikizumab-lbkz up to 25 mg/kg/week for 37 weeks, which was associated with plasma exposure (Cavg,ss) approximately 15 times the human exposure at the MRHD. No effects on reproductive organs or sperm analysis were observed in sexually mature male cynomolgus monkeys that were administered subcutaneous doses of lebrikizumab-lbkz up to 25 mg/kg/week for 13 weeks, which was associated with plasma exposure (Cavg,ss) approximately 11 times the human exposure at the MRHD.

CLINICAL PHARMACOLOGY SECTION.

12 CLINICAL PHARMACOLOGY. 12.1 Mechanism of Action. Lebrikizumab-lbkz is an IgG4 monoclonal antibody that binds with high affinity and slow off-rate to interleukin (IL)-13 and allows IL-13 to bind to IL-13R1 but inhibits human IL-13 signaling through the IL-4R/IL-13R1 receptor complex. IL-13 is naturally occurring cytokine that is involved in Type inflammation, which is an important component in the pathogenesis of atopic dermatitis. Lebrikizumab-lbkz inhibits IL-13-induced responses including the release of proinflammatory cytokines, chemokines and IgE. Lebrikizumab-lbkz-bound IL-13 can still bind IL-13R2 allowing subsequent internalization and natural clearance of IL-13.. 12.2 Pharmacodynamics. In clinical studies, lebrikizumab-lbkz reduced the levels of serum periostin, total immunoglobulin (IgE), CC chemokine ligand (CCL)17 [thymus and activation-regulated chemokine (TARC)], CCL18 [pulmonary and activation-regulated chemokine (PARC)], and CCL13 [monocyte chemotactic protein-4 (MCP-4)]. The clinical relevance of these biomarkers is not completely understood.The effectiveness of the maintenance dosage of EBGLYSS 250 mg every weeks was established using longitudinal exposure-response modeling. Longitudinal exposure-response model predictions were consistent for EBGLYSS maintenance dosages of 250 mg every weeks and 250 mg every weeks. 12.3 Pharmacokinetics. Lebrikizumab-lbkz steady-state exposure following either subcutaneous dose of 250 mg every weeks, every weeks, or every weeks in patients with atopic dermatitis are presented in Table 2. Lebrikizumab-lbkz exposure increases dose-proportionally over subcutaneous dose range of 37.5 to 500 mg. Lebrikizumab-lbkz steady state is achieved at Week following the approved recommended loading doses.Table 2: Lebrikizumab-lbkz Steady-State Exposure Following Subcutaneous Administration in Patients with Atopic DermatitisCmax Maximum concentration, Cavg Average concentration, Ctrough Trough concentrationa Following approved recommended loading dosesLebrikizumab-lbkz DosageaCmaxCavgCtrough250 mg every weeks108 mcg/mL100 mcg/mL87 mcg/mL250 mg every weeks63 mcg/mL51 mcg/mL36 mcg/mL250 mg every weeks43 mcg/mL26 mcg/mL11 mcg/mL. AbsorptionFollowing single subcutaneous 250 mg dose of lebrikizumab-lbkz, peak serum concentrations were achieved approximately to days post dose. The absolute bioavailability for subcutaneous dose was approximately 86%.Injection site locations did not influence the absorption of lebrikizumab-lbkz.. DistributionThe lebrikizumab-lbkz steady-state volume of distribution is 5.14 L.. Metabolism/EliminationLebrikizumab-lbkz is expected to be degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous IgG.The lebrikizumab-lbkz half-life is 24.5 days and clearance is 0.154 L/day. Lebrikizumab-lbkz exhibits linear elimination that is independent of dose.. Specific Populations. Age, Sex, RaceAge, sex, or race did not have significant effect on the pharmacokinetics of lebrikizumab-lbkz.. WeightLebrikizumab-lbkz trough concentrations were lower in subjects with higher body weight.. Patients with Renal or Hepatic ImpairmentSpecific clinical pharmacology studies to evaluate the effects of renal impairment and hepatic impairment on the pharmacokinetics of lebrikizumab-lbkz have not been conducted. Lebrikizumab-lbkz, as monoclonal antibody, is not expected to undergo significant hepatic or renal elimination. No clinically significant differences in the pharmacokinetics of lebrikizumab-lbkz were observed in patients with mild or moderate renal impairment.. Drug Interaction StudiesThe effect of lebrikizumab-lbkz on the PK of co-administered medications has not been studied.. 12.6 Immunogenicity. The observed incidence of anti-drug antibodies is highly dependent on the sensitivity and specificity of the assay. Differences in assay methods preclude meaningful comparisons of the incidence of anti-drug antibodies in the studies described below with the incidence of anti-drug antibodies in other studies, including those of EBGLYSS or of other lebrikizumab products.Antibodies to lebrikizumab-lbkz developed in 4/145 (2.8%) of subjects treated with EBGLYSS 250 mg every weeks followed by 250 mg every four weeks during the 12-month treatment period in EBGLYSS studies. Most of these antibodies were neutralizing and of low titers. Similar results were observed in pediatric subjects who received EBGLYSS up to 12 months. The presence of anti-drug antibodies was not associated with changes to pharmacokinetics, efficacy, or safety of lebrikizumab-lbkz. The clinical relevance of these findings is unknown because of the low occurrence of ADA.

CLINICAL STUDIES SECTION.

14 CLINICAL STUDIES. 14.1 Atopic Dermatitis. Three multicenter, randomized, double-blind, placebo-controlled trials, ADvocate 1, ADvocate and ADhere (NCT04146363, NCT04178967, NCT04250337) enrolled total of 1062 subjects 12 years of age and older with moderate-to-severe atopic dermatitis not adequately controlled by topical medication(s) and who were candidates for systemic therapy. total of 148 subjects (14%) were 12 to <18 years who weighed at least 40 kg and 914 (86%) were adult subjects. Disease severity was defined by an Investigators Global Assessment (IGA) score >=3 in the overall assessment of AD lesions on severity scale of to 4, an Eczema Area and Severity Index (EASI) score >=16 on scale of to 72, and minimum body surface area involvement of >=10%.At baseline, 50% of subjects were male, 63% were White, 11% were Black or African American, and 21% were Asian; 12.8% identified as Hispanic or Latino, 63% of subjects had baseline IGA score of (moderate AD) and 37% of subjects had baseline IGA of (severe AD). The baseline mean EASI was 29, and the baseline Pruritus Numeric Rating Scale (NRS) was on scale of 0-10. Of all subjects, 99% had received prior treatment for AD.In all three trials, subjects in the EBGLYSS group received subcutaneous injections of EBGLYSS 500 mg at Week and at Week 2, followed by 250 mg every other week (Q2W) through Week 16.To evaluate the maintenance and durability of response in the monotherapy trials (ADvocate and ADvocate 2), subjects originally randomized to EBGLYSS who achieved an IGA score of or 1, or at least 75% reduction in EASI from baseline [EASI-75] at Week 16 and did not require rescue therapy were re-randomized to an additional 36 weeks of either maintenance dose of EBGLYSS 250 mg Q2W (every weeks), EBGLYSS 250 mg Q4W (every weeks), or placebo.Subjects who did not achieve IGA or or EASI-75 at Week 16 or subjects who required rescue therapy during the first 16 weeks were treated with open-label EBGLYSS 250 mg Q2W.In the concomitant therapy trial (ADhere), subjects received EBGLYSS TCS or placebo TCS. Topical calcineurin inhibitors (TCI) were permitted for sensitive areas only, such as the face, neck, intertriginous and genital areas. All three trials assessed the primary endpoint, the proportion of subjects who achieved an IGA score of (clear) or (almost clear) and at least 2-point improvement from baseline at Week 16. Other evaluated outcomes at Week 16 included the proportion of subjects with EASI-75 and EASI-90, and improvement in itch severity as defined by reduction of at least points on an 11-point Pruritus NRS. ADvocate and ADvocate also evaluated the maintenance and durability of response through Week 52.The results of the EBGLYSS monotherapy trials (ADvocate and ADvocate 2) are presented in Table 3.Table 3: Efficacy Results of EBGLYSS Monotherapy at Week 16a in ADvocate and ADvocate in Subjects with Moderate-to-Severe Atopic Dermatitisa Subjects who received rescue therapy or discontinued treatment due to lack of efficacy were analyzed as non-responders. Data after treatment discontinuation due to any other reason were considered missing. Any missing data was imputed using MCMC-MI.b Subjects received 500 mg of EBGLYSS at Week and Week 2, and 250 mg Q2W up to Week 16c Primary endpoint. Responder was defined as subject with an IGA or (clear or almost clear) and reduction of >=2 points on 0-4 IGA scaleADvocate 1ADvocate 2EBGLYSS250 mgQ2WbPlaceboDifference from Placebo (95% CI)EBGLYSS250 mgQ2WbPlaceboDifference from Placebo (95% CI)Number of subjects283141--281146-- IGA or 1c 43%13%30%(22%, 38%)33%11%22%(14%, 30%) EASI-7559%16%42%(33%, 51%)52%18%33%(24%, 42%) EASI-9038%9%29%(21%, 36%)31%10%21%(13%, 28%)Number of subjects with baseline Pruritus NRS score >=4263130--253134-- Pruritus NRS >=4 point improvement46%13%33%(25%, 41%)40%12%28%(20%, 37%)The proportion of EBGLYSS-treated subjects who achieved IGA or (with >=2-point improvement from baseline) by visit in ADvocate and ADvocate are presented in Figure 1. Figure 1: Proportion of Subjects with Moderate-to-Severe Atopic Dermatitis achieving IGA or 1, with >=2-point improvement from baseline through Week 16 in ADvocate and ADvocate 2The proportion of EBGLYSS-treated subjects who achieved at least 4-point improvement from baseline in Pruritus NRS by visit in ADvocate and ADvocate are presented in Figure 2. Figure 2: Proportion of Subjects with Moderate-to-Severe Atopic Dermatitis with >=4-point improvement in Pruritus NRS through Week 16 in ADvocate or ADvocate 2Examination of age, sex, and White, Asian, Black or African American race subgroups did not identify differences in response to EBGLYSS among these subgroups. The database was not large enough to adequately assess differences in effects in other races. The results in the concomitant therapy trial (ADhere) at Week 16, where subjects received EBGLYSS TCS or placebo TCS were consistent with the results in the monotherapy trials (ADvocate and ADvocate 2).. Figure 1. Figure 2. Maintenance and Durability of Response (Week 16 to Week 52)EBGLYSS-treated subjects achieving IGA or or EASI-75, and who did not receive rescue therapy at Week 16 were re-randomized to 36 weeks of maintenance treatment with EBGLYSS 250 mg Q2W, EBGLYSS 250 mg Q4W, or placebo in ADvocate and ADvocate 2. The results are presented in Table 4.Table 4: Efficacy Results of EBGLYSS at Week 52 in ADvocate and ADvocate 2a in Subjects with Moderate-to-Severe Atopic Dermatitisa Subjects who received systemic rescue therapy, discontinued treatment due to lack of efficacy were analyzed as non-responders. Data after topical rescue medication or treatment discontinuation due to any other reason were considered missing. Any missing data were imputed using MCMC-MI.b Responder was defined as subject with an IGA or (clear or almost clear) and reduction of >=2 points on 0-4 IGA scaleADvocate 1ADvocate 2EBGLYSS 250 mgQ2WEBGLYSS 250 mg Q4WPlaceboEBGLYSS 250 mgQ2WEBGLYSS 250 mgQ4WPlaceboNumber of subjects who were IGA of or Responders at Week 16b454522323216 IGA of or 1b at Week 5276%74%47%65%81%50%Number of subjects who were EASI-75 Responders at Week 16616230515327 EASI-75 at Week 5279%79%61%77%85%72%.

CLINICAL TRIALS EXPERIENCE SECTION.

6.1 Clinical Trials Experience. Because clinical trials are conducted under widely varying and controlled conditions, adverse reaction rates observed in the clinical trials of drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.. Atopic DermatitisThe safety of EBGLYSS was evaluated across randomized, double-blind, placebo-controlled, multicenter trials in subjects with moderate-to-severe atopic dermatitis including phase trials (ADvocate 1, ADvocate 2, ADhere) and phase dose ranging trial (KGAF). In these trials, mean age was 37 years; 50% of subjects were male; 62% were White, 13% were Black, and 20% were Asian. In terms of co-morbid conditions, in the phase trials, 30% of the subjects had asthma, 50% had allergic rhinitis, 31% had food allergy, and 14% had allergic conjunctivitis at baseline.A total of 891 subjects were treated with EBGLYSS for at least year in the atopic dermatitis development program.ADvocate 1, ADvocate 2, and KGAF compared the safety of EBGLYSS monotherapy to placebo. ADhere compared the safety of EBGLYSS TCS to placebo TCS through 16 weeks. All subjects from the phase trials were allowed to enroll in the long-term extension study.. Weeks to 16Table summarizes the adverse reactions that occurred at rate of at least 1% in the EBGLYSS 250 mg every weeks monotherapy group, or in the EBGLYSS 250 mg every weeks TCS group, all at higher rate than placebo during the first 16 weeks of treatment.Table 1: Adverse Reactions Occurring in >=1% of the EBGLYSS Monotherapy Group or the EBGLYSS TCS Group in the Atopic Dermatitis Trials through Week 16a Integrated analysis of ADvocate 1, ADvocate 2, and the phase dose finding trial (KGAF)b Analysis of TCS concomitant therapy trial ADherec EBGLYSS 500 mg at Week and Week 2, followed by 250 mg every two weeksd Conjunctivitis cluster includes conjunctivitis, conjunctivitis allergic, and conjunctivitis bacteriale Injection Site Reactions cluster includes injection site-related: pain, erythema, reaction, discomfort, dermatitis, pruritus, swelling, and rashAdverse ReactionsEBGLYSS MonotherapyaEBGLYSS TCSbEBGLYSS250 mg Q2WcN 638n (%)PlaceboN 338n (%)EBGLYSS250 mg Q2Wc+ TCSN 145n (%)Placebo TCSN 66n (%)Conjunctivitisd 61 (10)10 (3)7 (5)0Injection Site Reactionse 16 (3)4 (1)4 (3)1 (2)Herpes Zoster3 (<1)02 (1)0In the monotherapy trials (ADvocate 1, ADvocate 2, and KGAF) through Week 16, the proportion of subjects who discontinued treatment due to adverse events was 2.4% in the EBGLYSS 250 mg every weeks group and 1.8% in the placebo group. In the TCS trial (ADhere) through Week 16, the proportion of subjects who discontinued treatment due to adverse events was 2.1% in the EBGLYSS 250 mg every weeks TCS group and 0% in the placebo TCS group. The most common adverse reactions leading to discontinuation of EBGLYSS compared to the placebo group were conjunctivitis and keratitis (0.6% vs. 0.3%), and injection site reactions (0.2% vs. 0) in the monotherapy trials; and conjunctivitis (0.7% vs. 0), and injection site reactions (0.7% vs. 0) in the TCS trial.. EosinophiliaIncreased post-baseline blood eosinophils were observed at higher frequency in EBGLYSS-treated subjects compared to placebo. During the first 16 weeks, eosinophilia (>5000 cells/mcL) was observed in 0.4% in the EBGLYSS-treated subjects and 0% in subjects receiving placebo. Blood eosinophil elevations were generally transient and did not result in discontinuation.. Safety Weeks 16 to 52Among those EBGLYSS-treated subjects who responded at Week 16 and who were re-randomized in the maintenance period of the monotherapy trials ADvocate and ADvocate 2, total of 113 and 118 subjects received EBGLYSS 250 mg every weeks or every weeks, respectively. The safety profile of EBGLYSS 250 mg every weeks was generally consistent with EBGLYSS every weeks during Weeks 16 to 52. The safety profile of EBGLYSS during maintenance treatment was generally consistent with the safety profile observed through Week 16.. Specific Adverse Drug Reactions. Conjunctivitis and KeratitisConjunctivitis was the most frequently reported eye disorder. Most cases of conjunctivitis and keratitis were mild or moderate in severity and recovered or resolved without treatment interruption or discontinuation.During the initial 16-week treatment period of the monotherapy trials, conjunctivitis, including allergic conjunctivitis, was reported by 61 subjects (10%) in the EBGLYSS 250 mg every weeks group and 10 subjects (3%) in the placebo group. In the TCS concomitant therapy trial, conjunctivitis was reported by subjects (5%) in the EBGLYSS 250 mg every weeks TCS group compared to 0% in the placebo TCS group. During the 16-week placebo-controlled induction period, 68 subjects reported 73 events of conjunctivitis. All events were nonserious and mild or moderate in severity. Conjunctivitis led to treatment discontinuation in subjects. The exposure adjusted incidence rate of conjunctivitis for subjects treated with EBGLYSS 250 mg every weeks was 30.6 events per 100 patient years through Week 16 (KGAF, ADvocate 1, ADvocate 2, ADhere).During the maintenance treatment period of the monotherapy trials (ADvocate and ADvocate 2) from 16 to 52 weeks, conjunctivitis, including allergic conjunctivitis, was reported by subjects (1.8%) in the EBGLYSS 250 mg every weeks group and 12 subjects (10.1%) in the EBGLYSS 250 mg every weeks group, compared to subjects (8.3%) in the placebo group. During the maintenance treatment period, 14 subjects treated with EBGLYSS reported 18 events of conjunctivitis. All events were mild or moderate in severity. Conjunctivitis led to treatment discontinuation in subjects in the EBGLYSS 250 mg every weeks group. The exposure adjusted incidence rate of conjunctivitis for subjects treated with EBGLYSS 250 mg every weeks was 18.3 events per 100 patient years and for those treated with EBGLYSS 250 mg every weeks was 20.6 events per 100 patient years through Week 52 (ADvocate 1, ADvocate 2, ADhere the long-term extension study).During the initial 16-week treatment period of the monotherapy trials, keratitis, including atopic and vernal keratoconjunctivitis, was reported by subjects (0.6%) in the EBGLYSS 250 mg every weeks group and subject (0.3%) in the placebo group. In the TCS concomitant therapy trial, vernal keratoconjunctivitis was reported by subject (0.7%) in the EBGLYSS 250 mg every weeks TCS group, compared to 0% in the placebo TCS group. All events were nonserious and mild or moderate in severity. Keratitis led to treatment discontinuation in subjects. The exposure adjusted incidence rate of keratitis for subjects treated with EBGLYSS 250 mg every weeks was 2.2 events per 100 patient years through Week 16 (KGAF, ADvocate 1, ADvocate 2, ADhere).During the maintenance treatment period of the monotherapy trials (ADvocate and ADvocate 2) from 16 to 52 weeks, atopic keratoconjunctivitis was reported by subject (0.8%) in the EBGLYSS 250 mg every weeks group, and vernal keratoconjunctivitis was reported by subject (0.9%) in the EBGLYSS 250 mg every weeks group, compared to 0% in the placebo group. One (0.9%) event of severe vernal keratoconjunctivitis in an EBGLYSS 250 mg every weeks subject led to treatment discontinuation. The exposure adjusted incidence rate of keratitis for subjects treated with EBGLYSS 250 mg every weeks was 1.0 event per 100 patient years and for those treated with EBGLYSS 250 mg every weeks was 0.7 events per 100 patient years through Week 52 (ADvocate 1, ADvocate 2, ADhere the long-term extension study).. Injection Site ReactionsInjection site reactions were reported by 3% of the EBGLYSS group and 1% of the placebo group in the first 16 weeks of the monotherapy trials. Incidence of injection site reactions declined with continued treatment. Most events were mild or moderate and recovered without treatment discontinuation.

CONTRAINDICATIONS SECTION.

4 CONTRAINDICATIONS. EBGLYSS is contraindicated in patients with prior serious hypersensitivity to lebrikizumab-lbkz or any excipients of EBGLYSS [see Warnings and Precautions (5.1)].. Prior serious hypersensitivity to lebrikizumab-lbkz or any excipients in EBGLYSS. (4).

DESCRIPTION SECTION.

11 DESCRIPTION. Lebrikizumab-lbkz, an interleukin-13 antagonist, is an immunoglobulin G4 (IgG4) monoclonal antibody that binds to interleukin (IL)-13 and inhibits IL-13 signaling. Lebrikizumab-lbkz is produced in Chinese Hamster Ovary (CHO) cells by recombinant DNA technology. Lebrikizumab-lbkz has an approximate molecular weight of 145 kDa.EBGLYSS (lebrikizumab-lbkz) injection is sterile, preservative free, clear to opalescent, colorless to slightly yellow to slightly brown solution for subcutaneous use. EBGLYSS is available as either 250 mg/2 mL single-dose prefilled pen or single-dose prefilled syringe with needle shield. The EBGLYSS prefilled pen and prefilled syringe with needle shield are not made with natural rubber latex.Each prefilled pen or prefilled syringe delivers 250 mg lebrikizumab-lbkz in mL solution which also contains glacial acetic acid (1.8 mg), histidine (6.2 mg), polysorbate 20 (0.6 mg), sucrose (119.6 mg) and Water for Injection. The pH is 5.4 6.0.

DOSAGE & ADMINISTRATION SECTION.

2 DOSAGE AND ADMINISTRATION. Prior to EBGLYSS treatment, complete all age-appropriate vaccinations according to current immunization guidelines. (2.1)The recommended dosage of EBGLYSS is 500 mg (two 250 mg injections) at Week and Week 2, followed by 250 mg (one injection) every weeks until Week 16 or later, when adequate clinical response is achieved. The maintenance dose of EBGLYSS is 250 mg every weeks or 250 mg every weeks. (2.2)Administer by subcutaneous injection. (2.4). Prior to EBGLYSS treatment, complete all age-appropriate vaccinations according to current immunization guidelines. (2.1). The recommended dosage of EBGLYSS is 500 mg (two 250 mg injections) at Week and Week 2, followed by 250 mg (one injection) every weeks until Week 16 or later, when adequate clinical response is achieved. The maintenance dose of EBGLYSS is 250 mg every weeks or 250 mg every weeks. (2.2). Administer by subcutaneous injection. (2.4). 2.1 Vaccination Prior to Administration of EBGLYSS. Complete all age-appropriate vaccinations according to current immunization guidelines [see Warnings and Precautions (5.4)].. 2.2 Recommended Dosage. The recommended subcutaneous dosage of EBGLYSS is an initial dose of 500 mg (two 250 mg injections) at Week and Week 2, followed by 250 mg every two weeks until Week 16 or later, when adequate clinical response is achieved. The maintenance dosage of EBGLYSS is 250 mg every four weeks or 250 mg every eight weeks [see Pharmacodynamics (12.2) and Clinical Studies (14.1)].. 2.3 Concomitant Topical Therapies. EBGLYSS can be used with or without topical corticosteroids (TCS). Topical calcineurin inhibitors (TCI) may be used, but reserved for sensitive areas only, such as the face, neck, intertriginous and genital areas.. 2.4 Important Administration Instructions. EBGLYSS is for subcutaneous administration.EBGLYSS is intended for use under the guidance of healthcare professional. Provide proper training to patients and/or caregivers on the subcutaneous injection technique of EBGLYSS. Adult patients may self-inject, or caregivers may give EBGLYSS after training in subcutaneous injection technique. For pediatric patients, caregivers may give injections after training in subcutaneous injection technique.Sites for injection include the abdomen, thigh, and back of the upper arm. Administration of EBGLYSS in the back of the upper arm may be performed by caregiver or healthcare provider.Alternate the injection site with each injection. Do not inject EBGLYSS within inches (5 cm) of the navel or into areas where the skin is tender, bruised, red, hard, or in an area of skin that is affected by atopic dermatitis or skin lesions. It is not necessary to allow EBGLYSS prefilled pen or EBGLYSS prefilled syringe to warm up to room temperature before use. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. EBGLYSS is clear to opalescent, colorless to slightly yellow to slightly brown solution. Do not use if the liquid contains visible particles, is discolored or cloudy [see Dosage Forms and Strengths (3), How Supplied/Storage and Handling (16)].Refer to the Instructions for Use for complete administration instructions with illustrations [see Instructions for Use].. EBGLYSS is for subcutaneous administration.. EBGLYSS is intended for use under the guidance of healthcare professional. Provide proper training to patients and/or caregivers on the subcutaneous injection technique of EBGLYSS. Adult patients may self-inject, or caregivers may give EBGLYSS after training in subcutaneous injection technique. For pediatric patients, caregivers may give injections after training in subcutaneous injection technique.. Sites for injection include the abdomen, thigh, and back of the upper arm. Administration of EBGLYSS in the back of the upper arm may be performed by caregiver or healthcare provider.. Alternate the injection site with each injection. Do not inject EBGLYSS within inches (5 cm) of the navel or into areas where the skin is tender, bruised, red, hard, or in an area of skin that is affected by atopic dermatitis or skin lesions.. It is not necessary to allow EBGLYSS prefilled pen or EBGLYSS prefilled syringe to warm up to room temperature before use. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. EBGLYSS is clear to opalescent, colorless to slightly yellow to slightly brown solution. Do not use if the liquid contains visible particles, is discolored or cloudy [see Dosage Forms and Strengths (3), How Supplied/Storage and Handling (16)].. Refer to the Instructions for Use for complete administration instructions with illustrations [see Instructions for Use].. 2.5 Missed Dose. If dose is missed, administer the dose as soon as possible. Thereafter, resume dosing at the regular scheduled time.

DOSAGE FORMS & STRENGTHS SECTION.

3 DOSAGE FORMS AND STRENGTHS. EBGLYSS is clear to opalescent, colorless to slightly yellow to slightly brown solution available as follows:Injection: 250 mg/2 mL in single-dose prefilled penInjection: 250 mg/2 mL (125 mg/mL) in single-dose prefilled syringe with needle shield. Injection: 250 mg/2 mL in single-dose prefilled pen. Injection: 250 mg/2 mL (125 mg/mL) in single-dose prefilled syringe with needle shield. Injection:250 mg/2 mL in single-dose prefilled pen (3)250 mg/2 mL (125 mg/mL) in single-dose prefilled syringe with needle shield (3). 250 mg/2 mL in single-dose prefilled pen (3). 250 mg/2 mL (125 mg/mL) in single-dose prefilled syringe with needle shield (3).

GERIATRIC USE SECTION.

8.5 Geriatric Use. Of the 1348 adult subjects with moderate-to-severe atopic dermatitis exposed to EBGLYSS, total of 123 were 65 years and older, and 29 subjects were 75 years and older. Clinical studies of EBGLYSS did not include sufficient numbers of subjects 65 years of age and older to determine whether they respond differently from younger adult subjects [see Clinical Pharmacology (12.3)].

HOW SUPPLIED SECTION.

16 HOW SUPPLIED/STORAGE AND HANDLING. How SuppliedEBGLYSS (lebrikizumab-lbkz) injection is sterile, preservative free, clear to opalescent, colorless to slightly yellow to slightly brown solution, available in single-dose prefilled pen or single-dose prefilled syringe with needle shield. Each prefilled pen and prefilled syringe with needle shield is designed to deliver 250 mg of EBGLYSS in mL.EBGLYSS is supplied as:Pack SizeNDCPrefilled Pen 250 mg/2 mL single-doseCarton of 10002-7772-11Prefilled syringe with needle shield 250 mg/2 mL (125 mg/mL) single-doseCarton of 10002-7797-11. Storage and HandlingStore refrigerated at 2C to 8C (36F to 46F).If necessary, EBGLYSS can be stored at room temperature up to 30C (86F) for up to days in the original carton. Dispose of EBGLYSS that has been left at room temperature for longer than days.Store in the original carton to protect from light until use.Do not freeze. Do not use EBGLYSS if it has been frozen.Do not shake.Do not microwave, run hot water over it, or leave it in direct sunlight.Not made with natural rubber latex.Discard the EBGLYSS single-dose prefilled pen or prefilled syringe with needle shield after use in puncture-resistant container.

IMMUNOGENICITY.

12.6 Immunogenicity. The observed incidence of anti-drug antibodies is highly dependent on the sensitivity and specificity of the assay. Differences in assay methods preclude meaningful comparisons of the incidence of anti-drug antibodies in the studies described below with the incidence of anti-drug antibodies in other studies, including those of EBGLYSS or of other lebrikizumab products.Antibodies to lebrikizumab-lbkz developed in 4/145 (2.8%) of subjects treated with EBGLYSS 250 mg every weeks followed by 250 mg every four weeks during the 12-month treatment period in EBGLYSS studies. Most of these antibodies were neutralizing and of low titers. Similar results were observed in pediatric subjects who received EBGLYSS up to 12 months. The presence of anti-drug antibodies was not associated with changes to pharmacokinetics, efficacy, or safety of lebrikizumab-lbkz. The clinical relevance of these findings is unknown because of the low occurrence of ADA.

INDICATIONS & USAGE SECTION.

1 INDICATIONS AND USAGE. EBGLYSS is indicated for the treatment of moderate-to-severe atopic dermatitis in adults and pediatric patients 12 years of age and older who weigh at least 40 kg whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable. EBGLYSS can be used with or without topical corticosteroids.. EBGLYSS(R) 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 who weigh at least 40 kg whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable. EBGLYSS can be used with or without topical corticosteroids. (1).

INFORMATION FOR PATIENTS SECTION.

17 PATIENT COUNSELING INFORMATION. Advise the patient and/or caregiver to read the FDA-approved patient labeling (Patient Information and Instructions for Use).. Administration Instructions: Provide guidance to patients and caregivers on proper subcutaneous injection technique, including aseptic technique, and how to use the prefilled pen and prefilled syringe correctly. Advise patients to follow sharps disposal recommendations [see Dosage and Administration (2.4), Instructions for Use].. Hypersensitivity: Advise patients to discontinue EBGLYSS and to seek immediate medical attention if they experience any symptoms of systemic hypersensitivity reactions [see Warnings and Precautions (5.1)].. Conjunctivitis and Keratitis: Advise patients to consult their healthcare provider if new onset or worsening eye symptoms develop [see Warnings and Precautions (5.2)].. Parasitic (Helminth) Infections: Advise patients to notify their healthcare provider if they present with clinical features consistent with helminthic infection [see Warnings and Precautions (5.3)].. Vaccinations: Advise patients that EBGLYSS may increase the risk of infection following administration of live vaccines and that vaccination with live vaccines is not recommended during EBGLYSS treatment. Instruct patients to inform the healthcare provider that they are taking EBGLYSS prior to potential vaccination [see Warnings and Precautions (5.4)].. Pregnancy: Inform patients to report their pregnancy to Eli Lilly and Company at 1-800-LillyRx (1-800-545-5979) [see Use in Specific Populations (8.1)].Eli Lilly and Company, Indianapolis, IN 46285, USAUS License No. 1891Copyright (C) 2024, 2026, Eli Lilly and Company. All rights reserved.Pat.: www.lilly.com/patentsEBG-0006-USPI-20260609.

INSTRUCTIONS FOR USE SECTION.

PREFILLED PEN INSTRUCTIONS FOR USE. INSTRUCTIONS FOR USEEBGLYSS(R) [EHB-glihs](lebrikizumab-lbkz)injection, for subcutaneous useSingle-Dose Prefilled PenThis Instructions for Use contains information on how to inject EBGLYSS.Before you use the EBGLYSS Prefilled Pen (Pen), read and carefully follow all the step-by-step instructions.Important information you need to know before injecting EBGLYSSYour healthcare provider should show you how to prepare and inject EBGLYSS using the Pen. Do not inject yourself or someone else until you have been shown how to inject EBGLYSS.Keep this Instructions for Use and read it as needed.Each EBGLYSS Pen contains dose of EBGLYSS. The Pen is for one-time use only. The EBGLYSS Pen contains glass parts. Handle it carefully. If you drop it on hard surface, do not use it. Use new EBGLYSS Pen for your injection.Your healthcare provider may help you decide where on your body to inject your dose. You can also read the Choose and clean your injection site section of these instructions to help you choose which area can work best for you.If you have vision or hearing problems, do not use EBGLYSS Pen without help from caregiver.See Storing EBGLYSS for important storage information.INSTRUCTIONS FOR USEBefore you use the EBGLYSS Pen, read and carefully follow all the step-by-step instructions.Parts of the EBGLYSS PenPreparing to inject EBGLYSSGather supplies and EBGLYSS Pen:EBGLYSS Pen from the refrigerator1 alcohol wipe1 cotton ball or piece of gauze1 sharps disposal container(See Disposing of EBGLYSS)Note: You do not need to allow your Pen to warm up to room temperature before use.Inspect the Pen and the medicineLeave the gray base cap on until you are ready to inject. Make sure you have the right medicine. The medicine inside should be clear. It may be colorless to slightly yellow to slightly brown.Do not use the Pen (see Disposing of EBGLYSS) if the:Pen looks damagedmedicine is frozenmedicine is cloudy, is discolored, or has particlesexpiration date printed on the label has passed Wash your hands with soap and waterChoose and clean your injection siteYour healthcare provider can help you choose the injection site that is best for you. Clean the injection site with an alcohol wipe and let dry. You or another person may inject into these areas.Stomach area (abdomen) --At least inches away from the belly button (navel). Front of thigh --At least inches above the knee and inches below the groin. Another person should inject into this area.Back of upper arm --Another person should inject into the back of your upper arm.Do not inject in the exact same spot every time. Do not inject into areas where the skin is tender, bruised, red, hard, or in an area of skin that is affected by eczema (atopic dermatitis) or other skin lesions. Injecting EBGLYSS1Uncap the PenMake sure the Pen is locked.When you are ready to inject, twist off the gray base cap and throw it away in your household trash. Do not put the gray base cap back on; this could damage the needle. Do not touch the needle inside the clear base.2Place and unlockPlace and hold the clear base flat and firmly against the skin.Keep the clear base on the skin, then turn the lock ring to the unlock position.3Press and hold for 15 secondsPress and hold the purple injection button and listen for loud clicks:First click: injection startedSecond click: injection completedThe injection may take up to 15 seconds.You will know the injection is complete when the gray plunger is visible.Disposing of EBGLYSSDispose of (throw away) the used PenPut the used EBGLYSS Pen in an FDA-cleared sharps disposal container right away after use.Do not throw away (dispose of) the EBGLYSS Pen in your household trash.If you do not have an FDA-cleared sharps disposal container, you may use household container that is:made of heavy-duty plastic,can be closed with tight-fitting, puncture-resistant lid, without sharps being able to come out,upright and stable during use,leak-resistant, andproperly labeled to warn of hazardous waste inside the container.When your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. There may be state or local laws about how you should throw away needles and syringes. For more information about safe sharps disposal, and for specific information about sharps disposal in the state you live in, go to the FDAs website at: http://www.fda.gov/safesharpsdisposal. Do not recycle your used sharps disposal container.Commonly asked questions Q.What if see air bubbles in the PenA.Air bubbles are normal. They will not harm you or affect your dose. Q.What if my Pen is not at room temperatureA.You do not need to allow your Pen to warm up to room temperature before injecting. Q. What if there is drop of liquid on the tip of the needle when remove the gray base cap A.A drop of liquid on the tip of the needle is normal. This will not harm you or affect your dose. Q. What if unlock the Pen and press the purple injection button before twisting off the gray base cap A.Do not remove the gray base cap. Throw away (dispose of) the Pen and use new one. Q. Do need to hold the purple injection button down until the injection is complete A.You do not need to hold the purple injection button down, but it may help you keep the Pen steady and firm against your skin. Q. What if the needle did not retract after my injection A.Do not touch the needle or replace the gray base cap. Store the Pen in safe place to avoid an accidental needlestick and contact Lilly at 1-800-Lilly-Rx (1-800-545-5979) for instructions on how to return the Pen. Q. What if there is drop of liquid or blood on my skin after my injection A.This is normal. Press cotton ball or gauze over the injection site. Do not rub the injection site. Q. How can tell if my injection is complete A.After you press the purple injection button, you will hear loud clicks. The second loud click tells you that your injection is complete. You will also see the gray plunger at the top of the clear base. The injection may take up to 15 seconds. Q. What if remove the Prefilled Pen before the second loud click or before the gray plunger stops moving A.You may not have received your full dose. Do not give another injection. Call your healthcare provider for help. Q. What if heard more than clicks during my injection, loud clicks and soft one. Did get my complete injection A.Some people may hear soft click right before the second loud click. That is the normal operation of the Prefilled Pen. Do not remove the Prefilled Pen from your skin until you hear the second loud click. If you have more questions about how to use the EBGLYSS Prefilled Pen: Call your healthcare providerScan this code to launch www.ebglyss.com Call 1-800-Lilly-Rx (1-800-545-5979) Visit www.ebglyss.comStoring EBGLYSS Store your Pen in the refrigerator between 36oF to 46oF (2C to 8C).EBGLYSS can be stored at room temperature up to days in the original carton. Do not store above 86F (30C). Throw away (dispose of) EBGLYSS that has been left at room temperature for longer than days.Store your Pen in the original carton to protect from light until use.Do not freeze your Pen. Do not shake your Pen.Do not microwave your Pen, or run hot water over it, or leave it in direct sunlight.Throw away (dispose of) your Pen if any of the above conditions are not followed. Keep your Pen and all medicines out of the reach of children. Read the Patient Information insert for EBGLYSS inside this box to learn more about your medicine.Eli Lilly and CompanyIndianapolis, IN 46285, USAUS License Number 1891EBGLYSS is registered trademark of Eli Lilly and Company.Copyright (C) 2024, 2026, Eli Lilly and Company. All rights reserved.This Instructions for Use has been approved by the U.S. Food and Drug Administration.Revised: FEB 2026 EBG-0004-PEN-IFU-20260227. Your healthcare provider should show you how to prepare and inject EBGLYSS using the Pen. Do not inject yourself or someone else until you have been shown how to inject EBGLYSS.. Keep this Instructions for Use and read it as needed.. Each EBGLYSS Pen contains dose of EBGLYSS. The Pen is for one-time use only. The EBGLYSS Pen contains glass parts. Handle it carefully. If you drop it on hard surface, do not use it. Use new EBGLYSS Pen for your injection.. Your healthcare provider may help you decide where on your body to inject your dose. You can also read the Choose and clean your injection site section of these instructions to help you choose which area can work best for you.. If you have vision or hearing problems, do not use EBGLYSS Pen without help from caregiver.. See Storing EBGLYSS for important storage information.. EBGLYSS Pen from the refrigerator. alcohol wipe. cotton ball or piece of gauze. sharps disposal container(See Disposing of EBGLYSS). Pen looks damaged. medicine is frozen. medicine is cloudy, is discolored, or has particles. expiration date printed on the label has passed. Stomach area (abdomen) --At least inches away from the belly button (navel). Front of thigh --At least inches above the knee and inches below the groin. Back of upper arm --Another person should inject into the back of your upper arm.. First click: injection started. Second click: injection completed. made of heavy-duty plastic,. can be closed with tight-fitting, puncture-resistant lid, without sharps being able to come out,. upright and stable during use,. leak-resistant, and. properly labeled to warn of hazardous waste inside the container.. Call your healthcare provider. Call 1-800-Lilly-Rx (1-800-545-5979). Visit www.ebglyss.com. Store your Pen in the refrigerator between 36oF to 46oF (2C to 8C).. EBGLYSS can be stored at room temperature up to days in the original carton. Do not store above 86F (30C). Throw away (dispose of) EBGLYSS that has been left at room temperature for longer than days.. Store your Pen in the original carton to protect from light until use.. Do not freeze your Pen. Do not shake your Pen.. Do not microwave your Pen, or run hot water over it, or leave it in direct sunlight.. Throw away (dispose of) your Pen if any of the above conditions are not followed.. Figure. Figure. Figure. Figure. Figure. Figure. Figure. Figure. Figure. Figure. Figure.

LACTATION SECTION.

8.2 Lactation. Risk SummaryThere are no data on the presence of lebrikizumab-lbkz in human milk, the effects on the breastfed infant, or the effects on milk production. Endogenous IgG and monoclonal antibodies are transferred in human milk. The effects of local gastrointestinal exposure and limited systemic exposure in the breastfed infant to lebrikizumab-lbkz are unknown. The developmental and health benefits of breastfeeding should be considered along with the mothers clinical need for EBGLYSS and any potential adverse effects on the breastfed infant from EBGLYSS or from the underlying maternal condition.

MECHANISM OF ACTION SECTION.

12.1 Mechanism of Action. Lebrikizumab-lbkz is an IgG4 monoclonal antibody that binds with high affinity and slow off-rate to interleukin (IL)-13 and allows IL-13 to bind to IL-13R1 but inhibits human IL-13 signaling through the IL-4R/IL-13R1 receptor complex. IL-13 is naturally occurring cytokine that is involved in Type inflammation, which is an important component in the pathogenesis of atopic dermatitis. Lebrikizumab-lbkz inhibits IL-13-induced responses including the release of proinflammatory cytokines, chemokines and IgE. Lebrikizumab-lbkz-bound IL-13 can still bind IL-13R2 allowing subsequent internalization and natural clearance of IL-13.

NONCLINICAL TOXICOLOGY SECTION.

13 NONCLINICAL TOXICOLOGY. 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility. Animal studies have not been conducted to evaluate the carcinogenic or mutagenic potential of lebrikizumab-lbkz.No effects on fertility parameters such as reproductive organs, reproductive hormones or menstrual cycle length were observed in sexually mature female cynomolgus monkeys that were administered intravenous doses of lebrikizumab-lbkz up to 25 mg/kg/week for 37 weeks, which was associated with plasma exposure (Cavg,ss) approximately 15 times the human exposure at the MRHD. No effects on reproductive organs or sperm analysis were observed in sexually mature male cynomolgus monkeys that were administered subcutaneous doses of lebrikizumab-lbkz up to 25 mg/kg/week for 13 weeks, which was associated with plasma exposure (Cavg,ss) approximately 11 times the human exposure at the MRHD.

OVERDOSAGE SECTION.

10 OVERDOSAGE. In the event of overdosage, contact Poison Control (1-800-222-1222) for the latest recommendations and monitor the patient for any signs or symptoms of adverse reactions and institute appropriate symptomatic treatment immediately.

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL.

PACKAGE LABEL Ebglyss 250 mg Prefilled PenEbglyss(R) (lebrikizumab-lbkz) injection250 mg 2 mL1 Single-Dose Prefilled Pen NDC 0002-7772-11 x 250 mg/2 mL Single-Dose Prefilled PenFor Subcutaneous Use OnlyRx onlyLilly. Ebglyss 250 mg Prefilled Pen Carton.

PEDIATRIC USE SECTION.

8.4 Pediatric Use. The safety and effectiveness of EBGLYSS have been established in pediatric patients 12 years of age and older who weigh at least 40 kg with moderate-to-severe atopic dermatitis whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable. total of 372 pediatric subjects were exposed to EBGLYSS with 270 subjects exposed to EBGLYSS for at least one year. The safety and effectiveness were generally consistent between pediatric and adult subjects [see Adverse Reactions (6.1), Clinical Studies (14.1)].The safety and effectiveness of EBGLYSS have not been established in pediatric patients younger than 12 years of age and pediatric patients 12 years and older who weigh less than 40 kg.

PHARMACODYNAMICS SECTION.

12.2 Pharmacodynamics. In clinical studies, lebrikizumab-lbkz reduced the levels of serum periostin, total immunoglobulin (IgE), CC chemokine ligand (CCL)17 [thymus and activation-regulated chemokine (TARC)], CCL18 [pulmonary and activation-regulated chemokine (PARC)], and CCL13 [monocyte chemotactic protein-4 (MCP-4)]. The clinical relevance of these biomarkers is not completely understood.The effectiveness of the maintenance dosage of EBGLYSS 250 mg every weeks was established using longitudinal exposure-response modeling. Longitudinal exposure-response model predictions were consistent for EBGLYSS maintenance dosages of 250 mg every weeks and 250 mg every weeks.

PHARMACOKINETICS SECTION.

12.3 Pharmacokinetics. Lebrikizumab-lbkz steady-state exposure following either subcutaneous dose of 250 mg every weeks, every weeks, or every weeks in patients with atopic dermatitis are presented in Table 2. Lebrikizumab-lbkz exposure increases dose-proportionally over subcutaneous dose range of 37.5 to 500 mg. Lebrikizumab-lbkz steady state is achieved at Week following the approved recommended loading doses.Table 2: Lebrikizumab-lbkz Steady-State Exposure Following Subcutaneous Administration in Patients with Atopic DermatitisCmax Maximum concentration, Cavg Average concentration, Ctrough Trough concentrationa Following approved recommended loading dosesLebrikizumab-lbkz DosageaCmaxCavgCtrough250 mg every weeks108 mcg/mL100 mcg/mL87 mcg/mL250 mg every weeks63 mcg/mL51 mcg/mL36 mcg/mL250 mg every weeks43 mcg/mL26 mcg/mL11 mcg/mL. AbsorptionFollowing single subcutaneous 250 mg dose of lebrikizumab-lbkz, peak serum concentrations were achieved approximately to days post dose. The absolute bioavailability for subcutaneous dose was approximately 86%.Injection site locations did not influence the absorption of lebrikizumab-lbkz.. DistributionThe lebrikizumab-lbkz steady-state volume of distribution is 5.14 L.. Metabolism/EliminationLebrikizumab-lbkz is expected to be degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous IgG.The lebrikizumab-lbkz half-life is 24.5 days and clearance is 0.154 L/day. Lebrikizumab-lbkz exhibits linear elimination that is independent of dose.. Specific Populations. Age, Sex, RaceAge, sex, or race did not have significant effect on the pharmacokinetics of lebrikizumab-lbkz.. WeightLebrikizumab-lbkz trough concentrations were lower in subjects with higher body weight.. Patients with Renal or Hepatic ImpairmentSpecific clinical pharmacology studies to evaluate the effects of renal impairment and hepatic impairment on the pharmacokinetics of lebrikizumab-lbkz have not been conducted. Lebrikizumab-lbkz, as monoclonal antibody, is not expected to undergo significant hepatic or renal elimination. No clinically significant differences in the pharmacokinetics of lebrikizumab-lbkz were observed in patients with mild or moderate renal impairment.. Drug Interaction StudiesThe effect of lebrikizumab-lbkz on the PK of co-administered medications has not been studied.

PREGNANCY SECTION.

8.1 Pregnancy. Risk SummaryAvailable data on lebrikizumab-lbkz use in pregnant women are insufficient to evaluate for drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Monoclonal antibodies are actively transported across the placenta (see Clinical Considerations). In animal reproduction studies, no effects on embryo-fetal development were observed after subcutaneous administration of lebrikizumab-lbkz to cynomolgus monkeys during organogenesis at doses up to 18 times the human exposure at the maximum recommended human dose (MRHD) (see Data).All pregnancies have background risk of birth defect, loss, or other adverse outcomes. The 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 to 4% and 15 to 20%, respectively.Report pregnancies to Eli Lilly and Company at 1-800-LillyRx (1-800-545-5979).. Clinical ConsiderationsFetal/Neonatal Adverse ReactionsTransport of endogenous IgG antibodies across the placenta increases as pregnancy progresses and peaks during the third trimester. Therefore, EBGLYSS may be present in infants exposed in utero. The potential clinical impact of EBGLYSS exposure in infants exposed in utero should be considered. DataAnimal DataIn an embryofetal development study, no malformations or embryofetal toxicity were observed in fetuses from pregnant cynomolgus monkeys administered lebrikizumab-lbkz during organogenesis at doses up to 150 mg/kg initial dose followed by 50 mg/kg per week by subcutaneous injection, which was associated with plasma exposure (Cavg,ss) approximately 18 times the human exposure at the MRHD. Lebrikizumab-lbkz crossed the placenta in monkeys.In prenatal and postnatal development study, pregnant cynomolgus monkeys were administered lebrikizumab-lbkz during organogenesis to parturition at doses up to 150 mg/kg initial dose followed by 50 mg/kg per week by subcutaneous injection, which was associated with plasma exposure (Cavg,ss) approximately 18 times the human exposure at the MRHD. No embryofetal toxicity or malformations, or effects on morphological, functional, or immunological development were observed in the infants from birth through months of age.

RECENT MAJOR CHANGES SECTION.

Dosage and Administration, single-dose prefilled syringe warming instructions (2.4) removed10/2025Dosage and Administration (2.2) 06/2026.

SPL PATIENT PACKAGE INSERT SECTION.

This Patient Information has been approved by the U.S. Food and Drug AdministrationRevised: 02/2026EBG-0002-PPI-202602PATIENT INFORMATIONEBGLYSS(R) (EHB-glihs) (lebrikizumab-lbkz) injection, for subcutaneous useWhat is EBGLYSSEBGLYSS is prescription medicine used to treat adults and children 12 years of age and older who weigh at least 88 pounds (40 kg) with moderate-to-severe eczema (atopic dermatitis) that is not well controlled with prescription therapies used on the skin (topical), or who cannot use topical therapies. EBGLYSS can be used with or without topical corticosteroids.It is not known if EBGLYSS is safe and effective in children less than 12 years of age or in children 12 years to less than 18 years of age who weigh less than 88 pounds (40 kg).Do not use EBGLYSS if you are allergic to lebrikizumab-lbkz or to any of the ingredients in EBGLYSS. See the end of this leaflet for complete list of ingredients in EBGLYSS.Before you use EBGLYSS, tell your healthcare provider about all your medical conditions, including if you:have parasitic (helminth) infectionare scheduled to receive any vaccinations. You should not receive live vaccine if you are treated with EBGLYSS.are pregnant or plan to become pregnant. It is not known if EBGLYSS will harm your unborn baby. If you become pregnant during treatment with EBGLYSS, you or your healthcare provider can call Eli Lilly and Company at 1-800-LillyRx (1-800-545-5979) to report the pregnancy.are breastfeeding or plan to breastfeed. It is not known if EBGLYSS passes into your breast milk.Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.How should take EBGLYSSSee the detailed Instructions for Use that comes with EBGLYSS for information about how to prepare and inject EBGLYSS and how to properly store and throw away (dispose of) used EBGLYSS prefilled pens and prefilled syringes.Use EBGLYSS exactly as prescribed by your healthcare provider.Your healthcare provider will tell you how much EBGLYSS to inject and how often to inject it.EBGLYSS comes as single-dose prefilled pen or prefilled syringe with needle shield.EBGLYSS is given as an injection under the skin (subcutaneous injection).If your healthcare provider decides that you or caregiver can give the injections of EBGLYSS, you or caregiver should receive training on the right way to prepare and inject EBGLYSS. Do not try to inject EBGLYSS until you have been shown the right way by your healthcare provider. In children 12 years of age and older, EBGLYSS should be given by caregiver.If you miss dose of EBGLYSS, inject the missed dose as soon as possible, then inject your next dose at your regular scheduled time.If you inject too much EBGLYSS (overdose), get medical help or contact Poison Center expert right away at 1-800-222-1222.Your healthcare provider may prescribe other medicines to use with EBGLYSS. Use the other prescribed medicines exactly as your healthcare provider tells you to.What are the possible side effects of EBGLYSSEBGLYSS can cause serious side effects, including:Allergic reactions. EBGLYSS can cause allergic reactions that may sometimes be severe. Stop using EBGLYSS and tell your healthcare provider or get emergency help right away if you get any of the following signs or symptoms:breathing problems or wheezingswelling of the face, lips, mouth, tongue, or throathivesitchingfainting, dizziness, feeling lightheadedskin rashcramps in your stomach area (abdomen)Eye problems. Tell your healthcare provider if you have any new or worsening eye problems, include eye pain or changes in vision, such as blurred vision.The most common side effects of EBGLYSS include:eye and eyelid inflammation, including redness, swelling, and itchinginjection site reactionsshingles (herpes zoster)These are not all of the possible side effects of EBGLYSS. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.How should store EBGLYSSStore EBGLYSS in the refrigerator between 36F to 46F (2C to 8C).EBGLYSS can be stored at room temperature up to 86F (30C) for up to days in the original carton. Throw away (dispose of) EBGLYSS that has been left at room temperature for longer than days.Store EBGLYSS in the original carton to protect from light until use.Do not freeze. Do not shake.Do not microwave EBGLYSS, or run hot water over it, or leave it in direct sunlight.Keep EBGLYSS and all medicines out of the reach of children.General information about the safe and effective use of EBGLYSS.Medicines are sometimes prescribed for purposes other than those listed in Patient Information leaflet. Do not use EBGLYSS for condition for which it is not prescribed. Do not give EBGLYSS to other people, even if they have the same symptoms you have. It may harm them. You can ask your pharmacist of healthcare provider for information about EBGLYSS that is written for health professionals.What are the ingredients in EBGLYSSActive ingredient: lebrikizumab-lbkz Inactive ingredient: glacial acetic acid, histidine, polysorbate 20, sucrose, and Water for Injection.EBGLYSS prefilled pen and prefilled syringe with needle shield are not made with natural rubber latex.EBGLYSS is registered trademark of Eli Lilly and Company. Eli Lilly and Company, Indianapolis, IN 46285 US License Number 1891 Copyright (C) 2024, 2026, Eli Lilly and Company. All rights reserved.For more information about EBGLYSS, call 1-800-545-5979 (1-800-Lilly-Rx) or go to www.ebglyss.com. have parasitic (helminth) infection. are scheduled to receive any vaccinations. You should not receive live vaccine if you are treated with EBGLYSS.. are pregnant or plan to become pregnant. It is not known if EBGLYSS will harm your unborn baby. If you become pregnant during treatment with EBGLYSS, you or your healthcare provider can call Eli Lilly and Company at 1-800-LillyRx (1-800-545-5979) to report the pregnancy.. are breastfeeding or plan to breastfeed. It is not known if EBGLYSS passes into your breast milk.. See the detailed Instructions for Use that comes with EBGLYSS for information about how to prepare and inject EBGLYSS and how to properly store and throw away (dispose of) used EBGLYSS prefilled pens and prefilled syringes.. Use EBGLYSS exactly as prescribed by your healthcare provider.. Your healthcare provider will tell you how much EBGLYSS to inject and how often to inject it.. EBGLYSS comes as single-dose prefilled pen or prefilled syringe with needle shield.. EBGLYSS is given as an injection under the skin (subcutaneous injection).. If your healthcare provider decides that you or caregiver can give the injections of EBGLYSS, you or caregiver should receive training on the right way to prepare and inject EBGLYSS. Do not try to inject EBGLYSS until you have been shown the right way by your healthcare provider. In children 12 years of age and older, EBGLYSS should be given by caregiver.. If you miss dose of EBGLYSS, inject the missed dose as soon as possible, then inject your next dose at your regular scheduled time.. If you inject too much EBGLYSS (overdose), get medical help or contact Poison Center expert right away at 1-800-222-1222.. Your healthcare provider may prescribe other medicines to use with EBGLYSS. Use the other prescribed medicines exactly as your healthcare provider tells you to.. Allergic reactions. EBGLYSS can cause allergic reactions that may sometimes be severe. Stop using EBGLYSS and tell your healthcare provider or get emergency help right away if you get any of the following signs or symptoms:. breathing problems or wheezing. swelling of the face, lips, mouth, tongue, or throat. hives. itching. fainting, dizziness, feeling lightheaded. skin rash. cramps in your stomach area (abdomen). Eye problems. Tell your healthcare provider if you have any new or worsening eye problems, include eye pain or changes in vision, such as blurred vision.. eye and eyelid inflammation, including redness, swelling, and itching. injection site reactions. shingles (herpes zoster). Store EBGLYSS in the refrigerator between 36F to 46F (2C to 8C).. EBGLYSS can be stored at room temperature up to 86F (30C) for up to days in the original carton. Throw away (dispose of) EBGLYSS that has been left at room temperature for longer than days.. Store EBGLYSS in the original carton to protect from light until use.. Do not freeze. Do not shake.. Do not microwave EBGLYSS, or run hot water over it, or leave it in direct sunlight.

SPL UNCLASSIFIED SECTION.

2.1 Vaccination Prior to Administration of EBGLYSS. Complete all age-appropriate vaccinations according to current immunization guidelines [see Warnings and Precautions (5.4)].

STORAGE AND HANDLING SECTION.

Storage and HandlingStore refrigerated at 2C to 8C (36F to 46F).If necessary, EBGLYSS can be stored at room temperature up to 30C (86F) for up to days in the original carton. Dispose of EBGLYSS that has been left at room temperature for longer than days.Store in the original carton to protect from light until use.Do not freeze. Do not use EBGLYSS if it has been frozen.Do not shake.Do not microwave, run hot water over it, or leave it in direct sunlight.Not made with natural rubber latex.Discard the EBGLYSS single-dose prefilled pen or prefilled syringe with needle shield after use in puncture-resistant container.

USE IN SPECIFIC POPULATIONS SECTION.

8 USE IN SPECIFIC POPULATIONS. 8.1 Pregnancy. Risk SummaryAvailable data on lebrikizumab-lbkz use in pregnant women are insufficient to evaluate for drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Monoclonal antibodies are actively transported across the placenta (see Clinical Considerations). In animal reproduction studies, no effects on embryo-fetal development were observed after subcutaneous administration of lebrikizumab-lbkz to cynomolgus monkeys during organogenesis at doses up to 18 times the human exposure at the maximum recommended human dose (MRHD) (see Data).All pregnancies have background risk of birth defect, loss, or other adverse outcomes. The 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 to 4% and 15 to 20%, respectively.Report pregnancies to Eli Lilly and Company at 1-800-LillyRx (1-800-545-5979).. Clinical ConsiderationsFetal/Neonatal Adverse ReactionsTransport of endogenous IgG antibodies across the placenta increases as pregnancy progresses and peaks during the third trimester. Therefore, EBGLYSS may be present in infants exposed in utero. The potential clinical impact of EBGLYSS exposure in infants exposed in utero should be considered. DataAnimal DataIn an embryofetal development study, no malformations or embryofetal toxicity were observed in fetuses from pregnant cynomolgus monkeys administered lebrikizumab-lbkz during organogenesis at doses up to 150 mg/kg initial dose followed by 50 mg/kg per week by subcutaneous injection, which was associated with plasma exposure (Cavg,ss) approximately 18 times the human exposure at the MRHD. Lebrikizumab-lbkz crossed the placenta in monkeys.In prenatal and postnatal development study, pregnant cynomolgus monkeys were administered lebrikizumab-lbkz during organogenesis to parturition at doses up to 150 mg/kg initial dose followed by 50 mg/kg per week by subcutaneous injection, which was associated with plasma exposure (Cavg,ss) approximately 18 times the human exposure at the MRHD. No embryofetal toxicity or malformations, or effects on morphological, functional, or immunological development were observed in the infants from birth through months of age.. 8.2 Lactation. Risk SummaryThere are no data on the presence of lebrikizumab-lbkz in human milk, the effects on the breastfed infant, or the effects on milk production. Endogenous IgG and monoclonal antibodies are transferred in human milk. The effects of local gastrointestinal exposure and limited systemic exposure in the breastfed infant to lebrikizumab-lbkz are unknown. The developmental and health benefits of breastfeeding should be considered along with the mothers clinical need for EBGLYSS and any potential adverse effects on the breastfed infant from EBGLYSS or from the underlying maternal condition.. 8.4 Pediatric Use. The safety and effectiveness of EBGLYSS have been established in pediatric patients 12 years of age and older who weigh at least 40 kg with moderate-to-severe atopic dermatitis whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable. total of 372 pediatric subjects were exposed to EBGLYSS with 270 subjects exposed to EBGLYSS for at least one year. The safety and effectiveness were generally consistent between pediatric and adult subjects [see Adverse Reactions (6.1), Clinical Studies (14.1)].The safety and effectiveness of EBGLYSS have not been established in pediatric patients younger than 12 years of age and pediatric patients 12 years and older who weigh less than 40 kg.. 8.5 Geriatric Use. Of the 1348 adult subjects with moderate-to-severe atopic dermatitis exposed to EBGLYSS, total of 123 were 65 years and older, and 29 subjects were 75 years and older. Clinical studies of EBGLYSS did not include sufficient numbers of subjects 65 years of age and older to determine whether they respond differently from younger adult subjects [see Clinical Pharmacology (12.3)].

WARNINGS AND PRECAUTIONS SECTION.

5 WARNINGS AND PRECAUTIONS. Hypersensitivity: Hypersensitivity reactions including angioedema and urticaria, have occurred after administration of EBGLYSS. Discontinue EBGLYSS in the event of serious hypersensitivity reaction. (5.1)Conjunctivitis and Keratitis: Report new onset or worsening eye symptoms to healthcare provider. (5.2)Parasitic (Helminth) Infections: Treat patients with pre-existing helminth infections before initiating EBGLYSS. If patients become infected while receiving EBGLYSS and do not respond to anti-helminth treatment, discontinue treatment with EBGLYSS until the infection resolves. (5.3)Vaccinations: Avoid use of live vaccines during treatment with EBGLYSS. (5.4). Hypersensitivity: Hypersensitivity reactions including angioedema and urticaria, have occurred after administration of EBGLYSS. Discontinue EBGLYSS in the event of serious hypersensitivity reaction. (5.1). Conjunctivitis and Keratitis: Report new onset or worsening eye symptoms to healthcare provider. (5.2). Parasitic (Helminth) Infections: Treat patients with pre-existing helminth infections before initiating EBGLYSS. If patients become infected while receiving EBGLYSS and do not respond to anti-helminth treatment, discontinue treatment with EBGLYSS until the infection resolves. (5.3). Vaccinations: Avoid use of live vaccines during treatment with EBGLYSS. (5.4). 5.1 Hypersensitivity. Hypersensitivity reactions, including angioedema and urticaria, have been reported with use of EBGLYSS. If serious hypersensitivity reaction occurs, discontinue EBGLYSS and institute appropriate therapy.. 5.2 Conjunctivitis and Keratitis. Conjunctivitis and keratitis adverse reactions have been reported in clinical trials.Conjunctivitis and keratitis occurred more frequently in atopic dermatitis subjects who received EBGLYSS compared to those who received placebo. Conjunctivitis was the most frequently reported eye disorder. Most subjects with conjunctivitis or keratitis recovered 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 EBGLYSS will influence the immune response against helminth infections by inhibiting IL-13 signaling.Treat patients with pre-existing helminth infections before initiating treatment with EBGLYSS. If patients become infected while receiving EBGLYSS and do not respond to antihelminth treatment, discontinue treatment with EBGLYSS until the infection resolves.. 5.4 Vaccinations. EBGLYSS may alter patients immunity and increase the risk of infection following administration of live vaccines. Prior to therapy with EBGLYSS, complete all age-appropriate vaccinations according to current immunization guidelines. Avoid use of live vaccines immediately prior to or during treatment with EBGLYSS. No data are available on the response to live vaccines.