TOPLINE

Rezpegaldesleukin, an interleukin-2 receptor agonist that selectively expands regulatory T cells (Tregs), significantly reduced disease severity vs placebo in patients with moderate-to-severe atopic dermatitis (AD) after 16 weeks of treatment.

METHODOLOGY

• Researchers conducted REZOLVE-AD, a phase 2b, randomized, double-blind, placebo-controlled trial across 107 sites in 10 countries of 393 adults (mean age 37.1 years; 52% women; 84% White, 9% Asian) with moderate-to-severe AD naive to biologic therapy.
• Participants were randomly assigned in a 3:3:3:2 ratio to receive subcutaneous rezpegaldesleukin 24 µg/kg every 2 weeks (n=104), rezpegaldesleukin 18 µg/kg every 2 weeks (n=106), rezpegaldesleukin 24 µg/kg every 4 weeks (n=110), or placebo every 2 weeks (n=73) for 16 weeks.
• The primary endpoint was percentage change in Eczema Area and Severity Index (EASI) score at week 16; secondary outcomes included EASI-75 (75% reduction in EASI), EASI-90 (90% reduction in EASI), validated Investigator Global Assessment for AD (vIGA-AD) response (score of 0 or 1 with at least a 2-point reduction), and itch Numerical Rating Scale (NRS) response (at least a 4-point improvement).

TAKEAWAY

• All three doses of rezpegaldesleukin significantly reduced EASI scores vs placebo (−31%) at week 16: −61% for rezpegaldesleukin 24 µg/kg every 2 weeks, P < .0001; −58% for 18 µg/kg every 2 weeks, P < .0001; and −53% for the 24 µg/kg every 4 weeks dose, P = .0002.
• At week 16, EASI-75 response rates with rezpegaldesleukin were 42% (24 µg/kg every 2 weeks), 46% (18 µg/kg every 2 weeks), and 34% (24 µg/kg every 4 weeks) vs 17% with placebo. Rezpegaldesleukin 24 µg/kg every 2 weeks led to significant reductions in EASI-90 response rates (25% vs 9% with placebo; P = .011), and vIGA-AD response rates were 20% vs 8% (P = .047).
• Among patients with a baseline itch NRS score of at least 4, rezpegaldesleukin 24 µg/kg and 18 µg/kg every 2 weeks doses achieved higher rates of NRS responses at week 16 (42% and 35% vs 16% with placebo; P = .0011 and .014, respectively).
• Rezpegaldesleukin treatment resulted in dose-dependent increases in activated Tregs, with up to sixfold increases from baseline in CD25bright Tregs and dose-dependent reductions in key AD biomarkers including thymus and activation-regulated chemokine (CCL17), periostin, macrophage-derived chemokine (CCL22), and interleukin-19. The treatment-emergent adverse event (TEAE) rate was 80% in patients who received rezpegaldesleukin; 2% were serious, and no related deaths were reported. The most common TEAEs were injection-site reactions.

IN PRACTICE

"To our knowledge, this is the first large, placebo-controlled trial validating the immunomodulatory effect of Tregs, now 25 years after their discovery, with no evidence of immunosuppression," the authors wrote. "Compared with available therapies and those in late-stage development, rezpegaldesleukin has a rapid onset of efficacy with a differentiating safety profile."

SOURCE

The study was led by Jonathan I. Silverberg, MD, Department of Dermatology, George Washington University School of Medicine, Washington. It was published online on August 22 in The Lancet.

LIMITATIONS

The study included only biologic treatment-naive adult patients, with most being White, which might limit generalizability to other populations. The analysis was not designed to detect statistically significant differences between rezpegaldesleukin treatment groups.

DISCLOSURES

The study was funded by Nektar Therapeutics. Silverberg and multiple authors reported receiving grants, speaker fees, advisory fees, consulting fees, and research support from Nektar Therapeutics and other pharmaceutical companies. Several authors disclosed being employees or stockholders of Nektar Therapeutics.

Additional author disclosures are reported in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.