New Data Highlights Nemolizumab with TCS Versus Calcineurin Inhibitors for Eczema

New phase 3 results from the ARCADIA 1 and 2 clinical trials were announced by Galderma highlighting the efficacy and safety data of nemolizumab in combination with topical corticosteroids (TCS), with or without topical calcineurin inhibitors (TCI), versus placebo with TCS, with or without TCI, for adolescents and adult patients with moderate-to-severe atopic dermatitis.¹

The announcement noted that the trials had successfully met their co-primary and key secondary endpoints, adding that nemolizumab therapy had led to substantially improved itch, skin lesions, and sleep disturbance by the 16-week mark versus placebo. The investigators had also found that there was noticeable itch relief among those treated as early as the first week.

“As a practicing dermatologist, I’m excited about the potential of nemolizumab for atopic dermatitis patients,” Jonathan Silverberg, MD, PhD, lead ARCADIA investigator and professor of dermatology at George Washington University School of Medicine and Health Sciences, said in a statement. “These phase III data demonstrate that, by blocking the activity of IL-31, nemolizumab could effectively address itch, skin lesions and sleep disturbance.”

Nemolizumab was designed as a first-in-class monoclonal antibody, formulated to target the interleukin-31 (IL-31) receptor alpha. The drug inhibits IL-31 signaling, which drives pruritus and contributes to disruption of the skin barrier and to inflammation among those with atopic dermatitis.

There were 2 pivotal phase 3 clinical trials in the ARCADIA program, both of which followed identical trial designs and involved over 1,700 individuals as subjects. These randomized, global, multicenter studies were carried out by Silverberg and colleagues in a double-blind, placebo-controlled manner to evaluate the results of subcutaneously administered nemolizumab on an every 4 week regimen, versus placebo.

The studies were focused on adolescent and adult individuals aged 12 and above who were known to have moderate-to-severe atopic dermatitis, with the initial treatment phase taking place for a total of 16 weeks. Both treatments were provided to the participants along with background TCS with or without topical calcineurin inhibitors.

There were 1,728 participants in the studies. A response was defined by the achievement of a clear or almost clear Investigator’s Global Assessment (IGA) score or a 75% or greater improvement in the Eczema Area and Severity Index score (EASI-75). These participants were then re-randomized for a period of maintenance treatment lasting up to 48 weeks.

The study’s conclusions showed that those given subcutaneous nemolizumab every 4 weeks alongside TCS, with or without TCI, were found to have statistically significant improvements in both co-primary endpoints versus those in the placebo arm with TCS, with or without TCI, following 16 weeks. Specifically, 36% and 38% of those given nemolizumab in ARCADIA 1 and 2 were able to get skin clearance versus 25% and 26% in the placebo arm of the study.

Additionally, the research team concluded that 44% and 42% of nemolizumab-treated subjects were able to reach at least an improvement of EASI-75, compared to 29% and 30% who had been featured in the placebo arm. A rapid response in terms of itch and statistically significant sleep disturbance improvements were also reported among those given nemolizumab in combination with TCS, with or without TCI, compared to the placebo.

Following a single week after therapy initiation, there were clinically meaningful itch improvements observed by the investigators.

“Many patients complain that chronic itch negatively impacts their overall quality of life,” Silverberg noted in his statement. “Reducing itch within just one week of treatment could significantly ease the burden of disease.”

By the 4-week mark, 16% of ARCADIA 1 and 2 participants were found by the research team to have achieved a state of being itch-free or nearly itch-free, compared to 4% and 3% of those in the placebo arms. The team reported that 38% and 34% of nemolizumab-treated individuals at the 16-week mark had a 4-point improvement at minimum on the sleep disturbance numerical rating scale, versus 20% and 16% of the placebo arms.

The investigators concluded that there was consistency in safety profiles between the nemolizumab and placebo arms of the studies. They found that most treatment-emergent adverse events had not been serious and had been of mild-to-moderate severity.

Following the ARCADIA 1 and 2 trial conclusions, the US Food and Drug Administration (FDA) accepted Galderma’s Biologics License Application for the drug, and a decision is expected by the year’s end.²

References

1. ^{Phase III Arcadia 1 and 2 trial primary results published in The Lancet: Galderma’s nemolizumab improves key aspects of atopic dermatitis – itch, skin lesions and sleep disturbance. Galderma. July 25, 2024. https://www.galderma.com/news/phase-iii-arcadia-1-and-2-trial-primary-results-published-lancet-galdermas-nemolizumab. Date accessed: July 25, 2024.}
2. ^{Smith T. Biologics License Application for Nemolizumab Accepted by FDA for Prurigo Nodularis, Atopic Dermatitis. HCPLive. February 14, 2024. https://www.hcplive.com/view/biologics-license-application-for-nemolizumab-accepted-by-fda-for-prurigo-nodularis-atopic-dermatitis. Date accessed: July 25, 2024.}