Date : 10/25/2024
Company Name : Eli Lilly and Company
Headquarter : United States
In first dedicated study of a selective IL-13 inhibitor in patients previously treated with dupilumab, the majority of patients had a history of inadequate response to dupilumab
EBGLYSS also provided meaningful improvements in difficult-to-treat face and hand dermatitis
The safety profile of EBGLYSS was consistent with previous Phase 3 studies and of the patients who reported eye-related events, facial dermatitis or inflammatory arthritis as the reason for prior dupilumab discontinuation, none reported similar events with EBGLYSS
INDIANAPOLIS, Oct. 25, 2024 /PRNewswire/ -- New results show Eli Lilly and Company's (NYSE: LLY) EBGLYSS improved skin (including hand and face) and itch among patients with moderate-to-severe atopic dermatitis (eczema) who were previously treated with dupilumab. These results from the Phase 3b ADapt study will be presented at the Fall Clinical Dermatology (FCD) Conference from Oct. 24-27 in Las Vegas.
EBGLYSS is an interleukin-13 (IL-13) inhibitor that selectively blocks IL-13 signaling with high binding affinity.2,3,4 The cytokine IL-13 is key in atopic dermatitis, driving the type-2 inflammatory cycle in the skin, leading to skin barrier dysfunction, itch, skin thickening and infection.
"Treatment isn't one-size-fits-all, and many patients with moderate-to-severe atopic dermatitis remain in need of an effective medicine to help manage the impact of the disease, especially in difficult-to-treat areas like face and hands," said Linda Stein Gold, M.D., investigator of the ADapt study, director of dermatology research and head of the Division of Dermatology for Henry Ford Health System in Detroit, Michigan. "These data showed that EBGLYSS improved skin symptoms and reduced itch for the majority of patients who had stopped using dupilumab and complement previously presented EBGLYSS data in biologic-naive patients, further supporting that a broad range of patients could benefit from this new and effective treatment option."
The ADapt study evaluated the efficacy and safety of EBGLYSS in patients with moderate-to-severe atopic dermatitis who were previously treated with dupilumab. To qualify for ADapt, patients must have discontinued dupilumab treatment due to inadequate response, intolerance or an adverse event, or other reasons (including cost or loss of access to the medicine). View an EBGLYSS patient photo from the ADapt study here.
The primary endpoint of the study was measured by at least 75 percent improvement in the Eczema Area and Severity Index (EASI-75) score at 16 weeks, which evaluates the extent and severity of the skin disease. Secondary endpoints at 16 and 24 weeks included Investigator Global Assessment (IGA) score of clear (0) or almost clear (1) skin with a reduction of at least two points from baseline and at least a four-point improvement in Pruritus NRS from baseline. Other secondary and exploratory endpoints were also included.1 The reported endpoints were as observed.
With EBGLYSS, 57 percent of patients at Week 16, and 60 percent of patients at Week 24 who were previously treated with dupilumab, achieved EASI-75. These results are similar to what was observed in the Phase 3 monotherapy trials of EBGLYSS in patients without prior exposure to dupilumab (ADvocate 1 and ADvocate 2). In addition, 46 percent of patients who were inadequate responders to dupilumab achieved EASI-75 response with EBGLYSS at Week 16.
Fifty-three percent and 62 percent of ADapt patients who discontinued dupilumab and began treatment with EBGLYSS also experienced itch relief (Pruritus NRS) with at least a four-point improvement from baseline at Week 16 and Week 24 respectively.
Patients in this study saw improvements in difficult-to-treat areas when treated with EBGLYSS. More than half of patients (52 percent) treated with EBGLYSS saw clear or almost clear face dermatitis at Week 24 (F-IGA 0,1 with a reduction of at least two points from baseline). Among patients with moderate-to-severe hand dermatitis at baseline (defined as ≥12), patients' modified total lesion symptom score (mTLSS), which measures extent and severity of hand dermatitis, decreased by 75 percent at Week 24.
Less than six percent of patients treated with EBGLYSS experienced an adverse event that led to treatment discontinuation.
The safety profile of EBGLYSS in ADapt was consistent with previous EBGLYSS Phase 3 studies in patients with moderate-to-severe atopic dermatitis, and no new safety signals were observed. The majority of adverse events were mild or moderate. Reported treatment-related side effects in the study were conjunctivitis and injection site reactions.
Of the 14 patients who discontinued dupilumab due to an adverse event, two patients discontinued EBGLYSS due to an adverse event. Of the 10 patients who discontinued dupilumab due to eye-related events, facial dermatitis or inflammatory arthritis, none reported similar events with EBGLYSS.
"This trial supports the growing body of data showing that health care providers can have confidence prescribing EBGLYSS as a first-line biologic treatment for moderate-to-severe atopic dermatitis, and reinforces that EBGLYSS provided a meaningful benefit among individuals who have already tried another biologic treatment such as dupilumab and may have more difficult-to-treat disease," said Mark Genovese, M.D., senior vice president of Lilly Immunology development.
Lilly will also present additional data at the Fall Clinical Dermatology conference, including new analyses from the ADjoin long-term extension study with data up to three years.
EBGLYSS was approved in the U.S. by the Food and Drug Administration (FDA) last month as a first-line biologic treatment for adults and children 12 years of age and older who weigh at least 88 pounds (40 kg) with moderate-to-severe atopic dermatitis that is not well controlled with topical prescription therapies.
EBGLYSS 250 mg/2 mL injection is dosed as a single monthly maintenance injection following the initial phase of treatment. The recommended initial starting dose of EBGLYSS is 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; after this, maintenance dosing is a single monthly injection (250 mg every four weeks).
EBGLYSS was also approved in the European Union in 2023, as well as in Japan in January 2024, with additional markets expected later this year.
Lilly has exclusive rights for development and commercialization of EBGLYSS in the U.S. and the rest of the world outside Europe. Lilly's partner Almirall S.A. has licensed the rights to develop and commercialize EBGLYSS for the treatment of dermatology indications, including eczema, in Europe.
*mTLSS is a composite measure of intensity of seven hand dermatitis signs and symptoms (erythema, edema, desquamation, fissures, hyperkeratosis/lichenification, pruritus/pain, and vesiculation, with total scores ranging from 0 to 21), used to assess improvement in hand dermatitis.
About ADapt
ADapt (NCT05369403), is an open-label, Phase 3b, 24-week study that evaluated the efficacy and safety of EBGLYSS in adults and adolescents (12 to less than 18 years of age and weighing ≥40 kg) with moderate-to-severe atopic dermatitis who were previously treated with dupilumab. Four or more weeks after discontinuing dupilumab, patients were treated with EBGLYSS and received a starting dosing of 500 mg (two 250 mg injections) at Week 0 and Week 2, followed by 250 mg every two weeks until Week 16. IGA 0,1 or EASI-75 responders at Week 16 received 250 mg once monthly and non-responders continued on 250 mg every two weeks until Week 24. Patients were allowed to stay on low and mid-potency topical corticosteroids.
From baseline to Week 16, data from the ADapt study was analyzed as observed and with non-responder imputation/multiple imputation (NRI/MI). After Week 16, Q2W and Q4W data from the ADapt study were pooled and analyzed as observed and with NRI/MI.
