Lebrikizumab Maintains EASI 90 Responses up to 38 Weeks After Discontinuation

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A post-hoc analysis from the ADvocate1 and ADvocate2 phase 3 clinical trials evaluated a subset of patients with atopic dermatitis who were randomly taken off of lebrikizumab (Ebglyss; Eli Lilly and Company) for 38 weeks and maintained stable EASI 90 responses up to week 52 with minimal remaining lebrikizumab serum concentrations. The data from the post-hoc analysis was presented at the 2024 Revolutionizing Alopecia Areata, Vitiligo, and Eczema Conference in Chicago, Illinois, held June 8-10.¹

Lebrikizumab is a biologic agent being evaluated for the treatment of adults and adolescents aged 12 years and older with moderate to severe atopic dermatitis that is inadequately controlled with topical or systemic treatments.

ADvocate1 (NCT04146363) and ADvocate2 (NCT04178967) are 2 randomized, double-blind, placebo-controlled, 52-week trials demonstrating the positive efficacy of lebrikizumab as monotherapy for moderate to severe atopic dermatitis. In the ADvocate trials, patients received 500mg loading doses of lebrikizumab at week 0 and week 2, followed by 250mg doses every 2 weeks from week 4 to week 14 of the induction period. At week 16, lebrikizumab responders were re-randomized 2:2:1 to receive lebrikizumab 250mg every 2 weeks, lebrikizumab 250mg every 4 weeks, or placebo every 2 weeks (lebrikizumab withdrawal).

Patients in the post-hoc analysis included lebrikizumab responders who were withdrawn from treatment and maintained EASI 90 for 80% of the visits during the withdrawal period, achieved EASI 90 at the week-52 visit, and did not use rescue medication.

EASI scores were assessed every 4 weeks from weeks 16 to 52 and lebrikizumab serum concentration levels were measured at weeks 16, 32, and 52. Silverberg et al evaluated the mean serum concentrations over time, the reduction in lebrikizumab concentrations and the number of half-lives during the withdrawal period.

Results

Overall, 17 (28%) of the 60 lebrikizumab responders who had their treatment stopped maintained EASI 90 for 80% of the visits during the 38-week withdrawal period, achieved EASI 90 at week 52, and did not use rescue medication.

At week 16, the mean serum lebrikizumab concentration was 92.4 (29.9) μg/mL. The mean serum concentrations decreased to 7.3 (14.0) μg/mL at week 32 and 0.15 (0.20) μg/mL at week 52, demonstrating 92% and <99% reductions, according to the data.

At week 52, 12 of the 16 patients had serum concentrations below the lower level of quantification (LLOQ: 0.09 μg/mL) for the clinical assay. In the population pharmacokinetic analysis, the mean elimination half-life for lebrikizumab was approximately 24.5 days. According to the study authors, lebrikizumab had “undergone approximately 5 half-lives at week 32 and 10.9 half-lives at week 52; it should be noted 5 to 7 half-lives for a biologic are often considered for a washout period.”

The post-hoc analysis demonstrated the ability of patients withdrawn from treatment with lebrikizumab to maintain EASI 90 responses up to week 52. “This is the first analysis that could provide additional insights into lebrikizumab therapy-free remission. Further studies are needed to identify and characterize this subpopulation of AD patients and lebrikizumab’s potential disease-modifying properties,” concluded Silverberg et al.

Lilly recently resubmitted its biologics license application for lebrikizumab in April 2024 and expects a decision from the US Food and Drug Administration in the second half of 2024.² Lebrikizumab was approved by the European Commission in November 2023 for the treatment of atopic dermatitis. Germany became the first country where lebrikizumab was available as a prescription. Almirall has the licensed rights to develop and commercialize lebrikizumab in Europe, while Lilly has exclusive rights for the development and commercialization of lebrikizumab in the US and the rest of the world.³

References

1. Silverberg J, Bieber T, Eyerich K, et al. EASI 90 response sustained up to 38 weeks after lebrikizumab withdrawal despite negligible serum concentrations. Poster presented at: 2024 Revolutionizing Alopecia Areata, Vitiligo, and Eczema Conference; June 8-10, 2024; Chicago, IL.
2. Lilly reports first-quarter 2024 financial results and raises full-year revenue guidance by $2 billion, highlights pipeline momentum. News release. Eli Lilly and Company. April 30, 2024. Accessed June 21, 2024. https://investor.lilly.com/news-releases/news-release-details/lilly-reports-first-quarter-2024-financial-results-and-raises
3. Almirall receives European Commission approval of EBGLYSS (lebrikizumab) for moderate-to-severe atopic dermatitis. News release. Almirall. November 17, 2023. Accessed June 21, 2024. https://www.almirall.com/newsroom/news/almirall-receives-european-commission-approval-of-ebglyss-lebrikizumab-for-moderate-to-severe-atopic-dermatitis