1 INDICATIONS AND USAGE EBGLYSS is indicated for the treatment of adults and 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.

EBGLYSS can be used with or without topical corticosteroids.

EBGLYSS ® is an interleukin-13 antagonist indicated for the treatment of adults and 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.

EBGLYSS can be used with or without topical corticosteroids.

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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 )] 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 a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Atopic Dermatitis The safety of EBGLYSS was evaluated across 4 randomized, double-blind, placebo-controlled, multicenter trials in subjects with moderate-to-severe atopic dermatitis including 3 phase 3 trials (ADvocate 1, ADvocate 2, ADhere) and 1 phase 2 dose ranging trial (KGAF).

In these 4 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 3 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 1 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 3 trials were allowed to enroll in the long-term extension study.

Weeks 0 to 16 Table 1 summarizes the adverse reactions that occurred at a rate of at least 1% in the EBGLYSS 250 mg every 2 weeks monotherapy group, or in the EBGLYSS 250 mg every 2 weeks + TCS group, all at a 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 16 a Integrated analysis of ADvocate 1, ADvocate 2, and the phase 2 dose finding trial (KGAF) b Analysis of TCS concomitant therapy trial ADhere c EBGLYSS 500 mg at Week 0 and Week 2, followed by 250 mg every two weeks d Conjunctivitis cluster includes conjunctivitis, conjunctivitis allergic, and conjunctivitis bacterial e Injection Site Reactions cluster includes injection site-related: pain, erythema, reaction, discomfort, dermatitis, pruritus, swelling, and rash Adverse Reactions EBGLYSS Monotherapy a EBGLYSS + TCS b EBGLYSS 250 mg Q2W c N = 638 n (%) Placebo N = 338 n (%) EBGLYSS 250 mg Q2W c + TCS N = 145 n (%) Placebo + TCS N = 66 n (%) Conjunctivitis d 61 (10) 10 (3) 7 (5) 0 Injection Site Reactions e 16 (3) 4 (1) 4 (3) 1 (2) Herpes Zoster 3 (<1) 0 2 (1) 0 In 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 2 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 2 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.

Eosinophilia Increased post-baseline blood eosinophils were observed at a 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 52 Among those EBGLYSS-treated subjects who responded at Week 16 and who were re-randomized in the maintenance period of the monotherapy trials ADvocate 1 and ADvocate 2, a total of 113 and 118 subjects received EBGLYSS 250 mg every 2 weeks or every 4 weeks, respectively.

The safety profile of EBGLYSS 250 mg every 4 weeks was generally consistent with EBGLYSS every 2 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 Keratitis Conjunctivitis 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 2 weeks group and 10 subjects (3%) in the placebo group.

In the TCS concomitant therapy trial, conjunctivitis was reported by 7 subjects (5%) in the EBGLYSS 250 mg every 2 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 3 subjects.

The exposure adjusted incidence rate of conjunctivitis for subjects treated with EBGLYSS 250 mg every 2 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 1 and ADvocate 2) from 16 to 52 weeks, conjunctivitis, including allergic conjunctivitis, was reported by 2 subjects (1.8%) in the EBGLYSS 250 mg every 2 weeks group and 12 subjects (10.1%) in the EBGLYSS 250 mg every 4 weeks group, compared to 5 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 2 subjects in the EBGLYSS 250 mg every 4 weeks group.

The exposure adjusted incidence rate of conjunctivitis for subjects treated with EBGLYSS 250 mg every 2 weeks was 18.3 events per 100 patient years and for those treated with EBGLYSS 250 mg every 4 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 4 subjects (0.6%) in the EBGLYSS 250 mg every 2 weeks group and 1 subject (0.3%) in the placebo group.

In the TCS concomitant therapy trial, vernal keratoconjunctivitis was reported by 1 subject (0.7%) in the EBGLYSS 250 mg every 2 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 2 subjects.

The exposure adjusted incidence rate of keratitis for subjects treated with EBGLYSS 250 mg every 2 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 1 and ADvocate 2) from 16 to 52 weeks, atopic keratoconjunctivitis was reported by 1 subject (0.8%) in the EBGLYSS 250 mg every 4 weeks group, and vernal keratoconjunctivitis was reported by 1 subject (0.9%) in the EBGLYSS 250 mg every 2 weeks group, compared to 0% in the placebo group.

One (0.9%) event of severe vernal keratoconjunctivitis in an EBGLYSS 250 mg every 2 weeks subject led to treatment discontinuation.

The exposure adjusted incidence rate of keratitis for subjects treated with EBGLYSS 250 mg every 2 weeks was 1.0 event per 100 patient years and for those treated with EBGLYSS 250 mg every 4 weeks was 0.7 events per 100 patient years through Week 52 (ADvocate 1, ADvocate 2, ADhere + the long-term extension study).

Injection Site Reactions Injection 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.