EBGLYSS
lebrikizumab
EBGLYSS™ was the third biologic to market targeting IL-13 for atopic dermatitis, behind DUPIXENT® (dupilumab; Sanofi and Regeneron Pharmaceuticals Inc) and ADBRY®/ADTRALZA® (tralokinumab; LEO Pharma). Nevertheless, its less frequent dosing, more selective inhibition of IL-13 and extensive efficacy and safety data will likely contribute to its uptake as first-line treatment of moderate-to-severe atopic dermatitis when topical corticosteroid (TCS) prescriptions are insufficient.
About EBGLYSS
- Eli Lilly and Co and Almirall
- IL-13-targeting mAb
- Subcutaneous injection to treat moderate-to-severe atopic dermatitis in adults and children 12 years of age and older weighing ≥88 pounds (40 kg)
- Every two weeks until adequate clinical response (starting at week 16), followed by monthly administration for maintenance
- ~70.5m prevalent cases of atopic dermatitis in the G7 markets in 2023
- ~40% of atopic dermatitis cases are moderate to severe
Why is it a drug to watch?
EBGLYSS joined Eli Lilly and Co’s immunology-focused pipeline when the company acquired Dermira Inc in 2020 for $1.1bn. Licensed to Almirall for the European market, EBGLYSS is also under investigation for the pediatric population as young as 6 months old, which will further establish its competitiveness against existing atopic dermatitis treatments.
EBGLYSS can be used with or without TCS and is dosed as a single monthly maintenance injection following the initial phase of treatment (two 250 mg injections each at Week 0 and Week 2, followed by 250 mg every two weeks until Week 16 or later when adequate clinical response is achieved). It is differentiated from existing IL-13-targeting treatments by its ability to prevent the formation of the IL-13Rα1/IL-4Rα heterodimer complex.
Approvals for EBGLYSS are based on positive data from three pivotal global phase 3 clinical trials:
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ADvocate 1 and ADvocate 2: adults and children (aged 12 to <18 years; weighing at least 40 kg) with moderate-to-severe eczema
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52-week randomized, double-blind, placebo-controlled, parallel-group studies
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EBGLYSS as monotherapy (16-week treatment induction period: 500 mg initially and at two weeks; maintenance period: 250 mg or placebo every two weeks) .
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38% achieved Investigator’s Global Assessment (IGA) 0 or 1 at 16 weeks (vs 12% with placebo); 10% at four weeks
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77% of responders maintained their results at one year with once-monthly dosing
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48% of responders who were switched to placebo at 16 weeks maintained their results at one year
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43% experienced itch relief at 16 weeks (vs 12% with placebo) measured using the Pruritus Numeric Rating Scale (PNRS)
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85% of itch responders maintained their results at one year with once-monthly dosing
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66% of itch responders who were switched to placebo at 16 weeks maintained their results at one year
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ADhere: adults and children (aged 12 to <18 years; weighing at least 40 kg) with moderate-to-severe eczema and symptoms inadequately controlled by topical medications at baseline
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16-week randomized, double-blind, placebo-controlled, parallel-group
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EBGLYSS in combination with TCS (500 mg initially and at two weeks; maintenance period: 250 mg or placebo every two weeks) vs placebo in combination with TCS .
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41.2% achieved IGA 0 or 1 with EBGLYSS + TCS vs 22.1% with placebo + TCS
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69.5% achieved 75% improvement in the Eczema Area and Severity Index (EASI-75) with EBGLYSS + TCS vs 42.2% with placebo + TCS
Other phase 3 trials include the following and are expected to contribute to label extensions in the future:
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ADore: global open-label study with adolescents (≥12 years to <18 years) with moderate-to-severe AD and weighing ≥40 kg
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EBGLYSS as monotherapy (two doses two weeks apart, followed by every two weeks from week 4 to week 52) for 52 weeks
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Primary endpoint: proportion of patients who discontinued study treatment due to AEs through the last treatment visit
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2.4% discontinued treatment due to AEs, and another 2.4% discontinued treatment due to SAEs
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65% reported at least one TEAE, most mild or moderate in severity 4
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62.6% achieved IGA 0 or 1 with ≥2-point improvement from baseline
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81.9% achieved EASI-75
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86.0% mean improvement in the EASI
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ADmirable: open-label study in the United States with adults and children (≥12 years old) with moderate-to-severe atopic dermatitis who self-report race other than White
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EBGLYSS as monotherapy (two doses two weeks apart, followed by every four weeks from week 16 to week 24) for 24 weeks
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Expected completion: December 2024
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ADapt: open-label study in the United States with adults and children (≥12 years old) with moderate-to-severe atopic dermatitis previously treated with DUPIXENT and not adequately controlled with topical medications
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EBGLYSS as monotherapy (two doses two weeks apart, followed by every four weeks from week 16 to week 24) for 24 weeks
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Expected completion: December 2024
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ADhope: open-label study in Germany, the Netherlands, Spain and the United Kingdom with adults and children (≥12 years old) with moderate-to-severe atopic dermatitis who failed topical therapies
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EBGLYSS as monotherapy (two doses two weeks apart, followed by every four weeks from week 16 to week 24)
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Expected completion: May 2025
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ADjoin: long-term global extension study with adults and children (≥12 years old) who received EBGLYSS in a prior study and adequately completed the study treatments and last patient visit of the parent trial
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EBGLYSS as monotherapy (every two or four weeks for 100 weeks)
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Expected completion: April 2025
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ADlong: long-term extension study in Germany and Poland with adults and children (≥12 years old) who completed treatment with EBGLYSS in ADjoin and their last participant assessment visit (week 100) in that study
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EBGLYSS as monotherapy (every four weeks for 104 weeks)
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Expected completion: April 2026
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ADorable-1: global RCT with children (6 months to <18 years old) with moderate-to-severe atopic dermatitis
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EBGLYSS in combination with TCS
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Expected completion: September 2025
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ADorable-2: long-term global extension study with children (6 months to <18 years old) with moderate-to-severe atopic dermatitis who adequately completed all visits of the ADorable 1 study
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EBGLYSS in combination with TCS
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Expected completion: June 2026
Review and approval status
December 2012
Fast track designation: U.S. FDA
October 2023
CRL: U.S. FDA
November 2023
Approved: EMA
December 2023
Approved: U.K. MHRA
January 2024
Approved: Japan MHLW
September 2024
Approved: U.S. FDA
Actual and expected launch:
- 2023: European Union, United Kingdom
- 2024: Japan, United States
- 2028: Mainland China
Patents estimated to expire beginning in 2024
Drug Timeline & Success Rates
Source: Cortellis Competitive Intelligence, Drug Timeline & Success Rates Prediction current as of October 31, 2024
How will EBGLYSS impact the market for atopic dermatitis?
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TCSs are the cornerstone of atopic dermatitis treatment based on their proven efficacy, low cost, manageable side effect profile and clinicians’ familiarity with the class. However, there is a need for effective systemic therapies that are more effective than TCSs.
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Eight treatment options have entered the market since 2020, and several emerging therapies will be launched over the next five years, which should meaningfully grow the drug-treated population. New and emerging therapies will benefit those with moderate-to-severe atopic dermatitis, and this segment will likely drive market growth.
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The biologic market is currently dominated by DUPIXENT, which first gained approval in 2017 and was expanded to children as young as six months in 2022. This dominance is not expected to change in the near future, especially given the real-world data that support clinical trial findings and physician familiarity with its use.
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However, the introduction of additional biologics such as EBGLYSS will likely help shift the treatment paradigm to greater biologic use and contribute to overall market share by biologics. Within this group, therapies targeting IL-13 are expected to dominate sales.
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The incremental improvements in tolerability and more convenient dosing with EBGLYSS could help it carve out some market share.
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Oral JAK inhibitors, such as CIBINQO® (Pfizer Inc), OLUMIANT® (Eli Lilly and Co) and RINVOQ® (AbbVie), that are also approved for atopic dermatitis in some countries and regions also provide highly efficacious orally administered treatment options. They will likely generate sizable revenues in this space; however, they are estimated to be used as post-biological options, at least until more real-world safety data are collected.
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These more expensive targeted therapies that are effective and safe have the potential to partially displace less expensive, mostly general topical and systemic mainstays of atopic dermatitis treatment.
What gaps in treatment does EBGLYSS fill?
Even with currently available therapies, many individuals with moderate-to-severe atopic dermatitis still struggle to control their disease, especially in the long term, or develop resistance, and severe itch can significantly impact their daily lives. Other negative impacts include impaired mental health, social stigma, poor sleep and disruptions to work and school. In addition, atopic dermatitis-related weakening of the skin barrier function, compounded by scratching, increases the risk of viral, bacterial and fungal skin infections, as well as strep throat, ear infections and urinary tract infections (UTIs). However, adherence to other treatment regimens, such as moisturizers, can mitigate this risk though they can be burdensome and require consistency in use and skin coverage. Administration of DUPIXENT and ADBRY/ADTRALZA can be challenging because of the injection frequency, which can be disruptive, and therefore a burden, for some patients and caregivers. More convenient, effective, and safer nonsteroidal topical or systemic treatments are needed for moderate-to-severe atopic dermatitis that is not adequately managed by available topical treatments or for those who have an incomplete response to DUPIXENT and other newer treatments. The once monthly administration of EBGLYSS and the lower risk of conjunctivitis than with DUPIXENT might give EBGLYSS an advantage.
What hurdles might it need to overcome to reach blockbuster status?
Uptake of EBGLYSS might be constrained by its status as the third IL-13-targeted therapy to market and competition from the currently available oral JAK inhibitors. In addition, many individuals with atopic dermatitis are well-served by over-the-counter (OTC) or generic agents. Also, many treatment providers prefer to prescribe generic moderate- to high-potency TCSs (applied once or twice weekly) as a prophylactic approach for moderate-to-severe atopic dermatitis with recurrent flares. This could limit the number of patients who would receive a higher priced targeted therapy. In addition, more expensive biologic therapies such as EBGLYSS might face reimbursement challenges.
