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 dosage of EBGLYSS is an initial dose of 500 mg (two 250 mg injections) at Week 0 and Week 2, followed by 250 mg every two weeks until Week 16 or later, when adequate clinical response is achieved. The maintenance dosage is 250 mg every four weeks [see 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 a 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 a caregiver or healthcare provider.
• Alternate the injection site with each injection. Do not inject EBGLYSS within 2 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.
• Before injection, remove EBGLYSS prefilled pen or EBGLYSS prefilled syringe from the refrigerator. If using:
  • EBGLYSS prefilled pen, it is not necessary to warm up to room temperature before use.
  • EBGLYSS prefilled syringe, leave at room temperature for 45 minutes without removing the needle cap. Do not warm EBGLYSS by using a heat source such as hot water, microwave, or direct sunlight. Protect EBGLYSS from light until use [see How Supplied/Storage and Handling (16)].
• Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. EBGLYSS is a 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 a dose is missed, administer the dose as soon as possible. Thereafter, resume dosing at the regular scheduled time.

5.1 Hypersensitivity

Hypersensitivity reactions, including angioedema and urticaria, have been reported with use of EBGLYSS. If a 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 a patient’s 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.

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.

8.1 Pregnancy

8.2 Lactation

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. A 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, a total of 123 were 65 years or older, and 29 subjects were 75 years or 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)].

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-13Rα1 but inhibits human IL-13 signaling through the IL-4Rα/IL-13Rα1 receptor complex. IL-13 is a naturally occurring cytokine that is involved in Type 2 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-13Rα2 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 E (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.

12.3 Pharmacokinetics

Lebrikizumab-lbkz steady-state exposure following either a subcutaneous dose of 250 mg every 2 weeks or every 4 weeks in patients with atopic dermatitis are presented in Table 2. Lebrikizumab-lbkz exposure increases dose-proportionally over a subcutaneous dose range of 37.5 to 500 mg. Lebrikizumab-lbkz steady state is achieved at Week 4 following the approved recommended loading doses.

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 drug products.

Antibodies to lebrikizumab-lbkz developed in 4/145 (2.8%) of subjects treated with EBGLYSS 250 mg every 2 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 titer. 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.

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.

14.1 Atopic Dermatitis

Three multicenter, randomized, double-blind, placebo-controlled trials, ADvocate 1, ADvocate 2 and ADhere (NCT04146363, NCT04178967, NCT04250337) enrolled a 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. A 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 Investigator's Global Assessment (IGA) score ≥3 in the overall assessment of AD lesions on a severity scale of 0 to 4, an Eczema Area and Severity Index (EASI) score ≥16 on a scale of 0 to 72, and a 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 a baseline IGA score of 3 (moderate AD) and 37% of subjects had a baseline IGA of 4 (severe AD). The baseline mean EASI was 29, and the baseline Pruritus Numeric Rating Scale (NRS) was 7 on a 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 0 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 1 and ADvocate 2), subjects originally randomized to EBGLYSS who achieved an IGA score of 0 or 1, or at least a 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 a maintenance dose of EBGLYSS 250 mg Q2W (every 2 weeks), EBGLYSS 250 mg Q4W (every 4 weeks), or placebo.

Subjects who did not achieve IGA 0 or 1 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 0 (clear) or 1 (almost clear) and at least a 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 a reduction of at least 4 points on an 11-point Pruritus NRS. ADvocate 1 and ADvocate 2 also evaluated the maintenance and durability of response through Week 52.

The results of the EBGLYSS monotherapy trials (ADvocate 1 and ADvocate 2) are presented in Table 3.

The proportion of EBGLYSS-treated subjects who achieved IGA 0 or 1 (with ≥2-point improvement from baseline) by visit in ADvocate 1 and ADvocate 2 are presented in Figure 1.

Figure 1: Proportion of Subjects with Moderate-to-Severe Atopic Dermatitis achieving IGA 0 or 1, with a ≥2-point improvement from baseline through Week 16 in ADvocate 1 and ADvocate 2

The proportion of EBGLYSS-treated subjects who achieved at least a 4-point improvement from baseline in Pruritus NRS by visit in ADvocate 1 and ADvocate 2 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 1 or ADvocate 2

Examination 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 1 and ADvocate 2).

How Supplied

EBGLYSS (lebrikizumab-lbkz) injection is a sterile, preservative free, clear to opalescent, colorless to slightly yellow to slightly brown solution, available in a single-dose prefilled pen or a 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 2 mL.

EBGLYSS is supplied as:

Storage and Handling

Store refrigerated at 2°C to 8°C (36°F to 46°F).

If necessary, EBGLYSS can be stored at room temperature up to 30°C (86°F) for up to 7 days in the original carton. Dispose of EBGLYSS that has been left at room temperature for longer than 7 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 a puncture-resistant container.

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 a 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, USA

US License No. 1891

Copyright © 2024, Eli Lilly and Company. All rights reserved.

EBG-0003-USPI-20241120