Rezpegaldesleukin Improves Atopic Dermatitis in Phase 2b Trial

Nektar Therapeutics announced the publication of 16-week induction results from the phase 2b REZOLVE-AD trial of rezpegaldesleukin in The Lancet, showing significant improvement in moderate to severe atopic dermatitis (AD) across all 3 dosing regimens tested. The trial met its primary endpoint of percent change from baseline in Eczema Area and Severity Index (EASI) at week 16, along with key secondary measures including EASI-75, EASI-90, itch, and body surface area (BSA). Results were announced August 25, 2026.¹

The publication marks the first large, randomized, placebo-controlled trial to support T-regulatory cell (T-reg) modulation as a therapeutic mechanism in a chronic inflammatory disease, according to Nektar. Rezpegaldesleukin targets the interleukin-2 (IL-2) receptor complex to preferentially stimulate T-reg proliferation and restore immune balance, rather than directly inhibiting inflammatory cytokines. Findings support continued development in the ongoing phase 3 ZENITH AD program.¹

REZOLVE-AD enrolled 393 biologic- and JAK inhibitor-naive adults with moderate-to-severe AD across 107 sites in 10 countries. The global, randomized, double-blind, placebo-controlled phase 2b trial assigned patients to 1 of 3 rezpegaldesleukin regimens, 24 μg/kg every 2 weeks (q2w), 18 μg/kg q2w, or 24 μg/kg every 4 weeks (q4w), or to placebo, for a 16-week induction period. The primary endpoint was mean percent change from baseline in EASI at week 16.¹

All 3 dosing regimens met the primary endpoint with statistically significant, dose-dependent reductions in EASI versus placebo. Patients on 24 μg/kg q2w achieved a 61% mean EASI reduction, followed by 58% for 18 μg/kg q2w and 53% for 24 μg/kg q4w, compared with 31% for placebo (P < .0001, P < .0001, and P = .0002, respectively). Investigators observed significant EASI improvement as early as week 2 in the 24-μg/kg arms and by week 4 across all active arms, with responses deepening through week 16.¹

Efficacy was consistent across patients with moderate (vIGA-AD score of 3) and severe (vIGA-AD score of 4) baseline disease.¹

Rezpegaldesleukin Secondary Endpoints and Safety in REZOLVE-AD

Rezpegaldesleukin 24 μg/kg q2w produced significant improvement over placebo across key secondary endpoints, including EASI-75 (42% vs 17%), EASI-90 (25% vs 9%), and vIGA-AD 0/1 response (20% vs 8%). Itch improved substantially, with 42% of patients achieving a 4-point reduction on the Itch Numerical Rating Scale versus 16% on placebo, and BSA declined by 54% versus 17%. Among patients with severe baseline itch (Itch NRS score of 7 or greater), response rates reached 54% and 49% for the 24 μg/kg q2w and 18 μg/kg q2w arms, respectively, versus 24% for placebo.¹

Patient-reported outcomes also favored rezpegaldesleukin 24 μg/kg q2w, including a 4-point reduction in Dermatology Life Quality Index score (72% vs 54%), a 5-point reduction in Atopic Dermatitis Control Tool score (67% vs 35%), a 4-point reduction in Pain Numerical Rating Scale score (45% vs 22%), and a 1.25-point reduction in Atopic Dermatitis Sleep Scale item 1 (57% vs 30%). Rezpegaldesleukin dose-dependently reduced AD biomarkers, including TARC/CCL17, periostin, MDC/CCL22, and interleukin-19, in patients with elevated baseline levels, consistent with T-reg-driven immunomodulation. According to Nektar, the safety profile during the 16-week induction period was consistent with prior studies of the agent.¹

Serious adverse events occurred in 2% of patients, with no deaths reported and no increased risk of infections or conjunctivitis, both safety signals associated with currently approved AD therapies.¹

Jonathan I. Silverberg, MD, PhD, MPH, professor of dermatology at George Washington University School of Medicine and principal investigator of the REZOLVE-AD study, said, "These results represent the first large, randomized, placebo-controlled trial to demonstrate that selectively expanding regulatory T cells can translate into clinically meaningful improvements across both physician-assessed and patient-reported outcomes in patients with atopic dermatitis. The rapid onset of efficacy, paired with consistency of responses across disease severity and a good safety profile, highlights the unique promise of rezpegaldesleukin. With a T-reg mechanism that works upstream of currently available targeted agents, we have the opportunity with rezpegaldesleukin to alter the treatment paradigm and provide a novel alternative for the many patients with moderate-to-severe atopic dermatitis who are inadequately treated today."¹

We have the opportunity with rezpegaldesleukin to alter the treatment paradigm and provide a novel alternative for the many patients with moderate to severe atopic dermatitis who are inadequately treated today. — Jonathan I. Silverberg, MD, PhD, MPH

Rezpegaldesleukin is also being developed for alopecia areata and type 1 diabetes. The phase 3 ZENITH AD-1 and ZENITH AD-2 trials, initiated in July 2026, are enrolling biologic- and JAK inhibitor-naive patients, while ZENITH AD-3 will enroll patients with prior systemic biologic or JAK inhibitor experience beginning in September 2026. The FDA granted Fast Track designation to rezpegaldesleukin for moderate-to-severe AD in February 2025 and for severe alopecia areata in July 2025.¹

References

1. Nektar announces publication in The Lancet of positive phase 2b REZOLVE-AD 16-week induction results of rezpegaldesleukin in moderate-to-severe atopic dermatitis. News release. Nektar Therapeutics. August 25, 2026. https://ir.nektar.com/news-releases/news-release-details/nektar-announces-publication-lancet-positive-phase-2b-rezolve-ad
2. REZOLVE-AD 16-week induction results of rezpegaldesleukin in moderate-to-severe atopic dermatitis. Lancet. Published online August 25, 2026. Accessed August 25, 2026. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(26)01143-8/fulltext