ARCADIA: Nemolizumab Achieves Significant Itch Reduction by Day 2 of Treatment

Jonathan Silverberg, MD, PhD, MPH
Credit: George Washington University

A post-hoc analysis of data from a pair of phase 3 trials is providing dermatologists with additional insight into the effects of nemolizumab among patients with atopic dermatitis ahead of a potential FDA decision expected later in 2024.

Presented at the Revolutionizing Atopic Dermatitis 2024 Annual Meeting, the analysis, which included data from the ARCADIA 1 and ARCADIA 2 trials, offer perspective on the speed of onset of itch relief and sleep improvements achieved with use of nemolizumab among patients with moderate-to-severe atopic dermatitis, with results suggesting significant improvements in itch were achieved by the second day for both trials.

“Treatment with nemolizumab plus [topical corticosteroids]/[topical calcineurin inhibitors] resulted in rapid, statistically and clinically significant improvements in itch in moderate-to-severe atopic dermatitis,” investigators wrote.

ARCADIA 1 and ARCADIA 2 were identical, randomized, double-blind, placebo-controlled, multicenter, parallel-group, 16-week phase 3 clinical trials launched by Galderma in 2019 with the intent of exploring the efficacy and safety of nemolizumab in adult and adolescent patients with moderate-to-severe atopic dermatitis. The trials, which were initially presented at the 2023 European Academy of Dermatology and Venereology congress, were designed with co-primary endpoints, which were defined as the proportion of subjects with an Investigator's Global Assessment (IGA) success and at least a 2-grade improvement or better from baseline to week 16 as well as the proportion of subjects with a 75% reduction or greater in Eczema Area and Severity Index (EASI-75) at week 16.^1,2,3

Results of the trial’s demonstrated 35.6% and 37.7% of nemolizumab-treated patients in ARCADIA 1 and 2, respectively, achieved IGA success relative to 24.6% and 26.0% of the placebo groups (P <.0006; P = .001). Analysis of EASI-75 attainment revealed 43.5% and 42.1% of nemolizumab-treated patients in ARCADIA 1 and 2, respectively, achieved EASI-75 relative to 29.0% and 30.2% of the placebos group (P <.0001; P = .0011).³

Coming less than 4 months after Galderma announced the acceptance of their regulatory filing for nemolizumab in atopic dermatitis and prurigo nodularis, the presentation from Jonathan Silverberg, MD, PhD, MPH, professor of dermatology and director of clinical research at the George Washington University School of Medicine and Health Science, examined the speed of onset of itch relief and sleep improvements with nemolizumab. With this in mind, investigators designed the post-hoc analysis of time to significance for changes in Peak Pruritus Numeric Rating Scale (PP-NRS) with nemolizumab as well as time to achieve a 4-point or greater improvement in PP-NRS relative to placebo-treated patients.^1,2,3

Upon analysis, results indicated significant improvements in itch least squares (LS) mean change from baseline in PP-NRS were noted in nemolizumab-treated patients relative to their placebo-treated counterparts by day 1 in ARCADIA 1 (-0.9 [SE, 0.08] vs -0.4 [SE, 0.10]) and ARCADIA 2 (-1.1 [SE, 0.09] vs -0.4 [SE, 0.12])(P <.001 for all). By day 14, the LS mean change in PP-NRS reached -2.4 (SE, 0.08) with nemolizumab and -1.2 (SE, 0.11) with placebo in ARCADIA 1 and -2.3 (SE, 0.09) with nemolizumab and -0.9 (SE, 0.12) with placebo in ARCADIA 2 (P <.001 for all).¹

Further analysis suggested significantly greater proportions of nemolizumab-treated relative to placebo-treated patients achieved 4-point or greater improvement in PP-NRS by day 2 in ARCADIA 1 (9.4% vs 3.4%, P <.01) and day 1 in ARCADIA 2 (8.2% vs 1.9%; P <.001). Investigators highlighted these differences were sustained through day 14 in both ARCADIA 1 (22.7% vs 10.6%; P <.0001) and ARCADIA 2 (23.4% vs 6.8%; P <.0001).¹

References:

1. Silverberg JI, Stein-Gold L, Thaçi C, et al. Nemolizumab elicits fast itch response in atopic dermatitis within 2 days: A post hoc analysis of ARCADIA 1 and 2 data. Abstract presented at Revolutionizing Atopic Dermatitis 2024. Chicago, Il. June 08-10, 2024.
2. Galderma. Galderma announces regulatory filing acceptance for nemolizumab in prurigo nodularis and atopic dermatitis in the U.S. and EU. Galderma. February 14, 2024. Accessed June 11, 2024. https://www.galderma.com/news/galderma-announces-regulatory-filing-acceptance-nemolizumab-prurigo-nodularis-and-atopic.
3. Galderma. Galderma @ EADV 2023: Phase III trials demonstrate nemolizumab’s efficacy and rapid onset of action in atopic dermatitis and prurigo nodularis. Galderma. October 11, 2023. Accessed June 11, 2024. https://www.galderma.com/news/galderma-eadv-2023-phase-iii-trials-demonstrate-nemolizumabs-efficacy-and-rapid-onset-action.