Announcement • 11h
Nektar Therapeutics Publishes Positive Phase 2B Rezolve-Ad 16-Week Induction Results of Rezpegaldesleukin in Moderate-To-Severe Atopic Dermatitis
Nektar Therapeutics announced the publication of peer-reviewed data from the 16-week induction period of REZOLVE-AD, a global, randomized, double-blind, placebo-controlled Phase 2b study evaluating rezpegaldesleukin in adults with moderate-to-severe atopic dermatitis (AD). The publication in The Lancet provides the medical and scientific community with the full reporting of efficacy, safety, pharmacodynamics, pharmacokinetics, and biomarker findings from the 16-week induction period of the Phase 2b trial. Rezpegaldesleukin is a first-in-class regulatory T-cell (T-reg) biologic designed to address imbalances in the immune system that underlie many autoimmune disorders and chronic inflammatory conditions. It targets the IL-2 receptor complex to preferentially stimulate the proliferation of T-regs to restore immune balance. The REZOLVE-AD trial was conducted across 107 sites in 10 countries, analyzing 393 biologic- and JAK inhibitor-naive adults with moderate-to-severe atopic dermatitis. Patients were randomized to one of three rezpegaldesleukin dosing regimens (24 µg/kg every two weeks, 18 µg/kg every two weeks, or 24 µg/kg every four weeks) or placebo for a 16-week induction period, with the primary endpoint of mean percent change from baseline in Eczema Area and Severity Index (EASI) at Week 16. All three dosing regimens met the primary endpoint: Patients treated with rezpegaldesleukin showed statistically significant, dose-dependent improvement in mean percent reduction in EASI from baseline at Week 16: 61%, 58%, and 53% for the 24 µg/kg every two weeks, 18 µg/kg every two weeks, and 24 µg/kg every four weeks arms, respectively, compared with 31% for placebo. Key secondary endpoints were met: Significant improvements over placebo were observed in EASI-75 (42% vs. 17%), EASI-90 (25% vs. 9%), Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) 0/1 response (20% vs. 8%), Itch Numerical Rating Scale (NRS) 4-point reduction (42% vs. 16%), and body surface area (BSA) change from baseline (-54% vs. -17%), all favoring rezpegaldesleukin 24 µg/kg every two weeks. Key Patient-Reported Outcome (PRO) Assessments: Rezpegaldesleukin demonstrated statistically significant improvements in patient reported outcomes over placebo at week 16 including = 4-point reduction in Daily Life Quality Index (DLQI) (72% vs. 54%), = 5-point reduction in Atopic Dermatitis Control Tool (ADCT) (67% vs. 35%), = 4-point reduction in Pain Numeric Rating (Pain NRS) (45% vs. 22%) and = 1.25-point reduction in Atopic Dermatitis Sleep Scale (ADSS) item 1 (57% vs. 30%), all favoring rezpegaldesleukin 24 µg/kg every two weeks. Rapid onset with deepening responses over time: Significant EASI improvement was observed as early as Week 2 in the 24 µg/kg dose arms and by Week 4 across all rezpegaldesleukin arms, with responses continuing to deepen through Week 16, indicating potential for further benefit with extended induction treatment. Consistent efficacy across baseline disease severity: Rezpegaldesleukin demonstrated similar efficacy in patients with moderate (vIGA-AD score 3) and severe (vIGA-AD score 4) disease at baseline. Meaningful itch relief, including in patients with severe itch: Among patients with a baseline Itch NRS score of 7 or greater, Itch NRS response rates were 54% and 49% for the 24 µg/kg every two weeks and 18 µg/kg every two weeks arms, respectively, compared with 24% for placebo. Favorable and differentiated safety profile: Safety data for rezpegaldesleukin for the 16-week induction period were consistent with the previously observed and reported safety profile. Serious adverse events were rare (2%), with no deaths reported during the 16-week induction period and no increased risk of infections, conjunctivitis, or other safety signals associated with currently approved AD therapies. Biomarker data support mechanism of action: Rezpegaldesleukin dose-dependently reduced key AD biomarkers including TARC/CCL17, periostin, MDC/CCL22, and interleukin-19 in patients with elevated baseline levels, consistent with upstream immunomodulation through T-reg restoration. The results from this trial, corroborated by biomarker evidence of rezpegaldesleukin's mechanistic activity, support a central role of T-reg imbalance in the pathogenesis of atopic dermatitis and IL-2 receptor agonism as an important therapeutic target. Phase 3 program underway: Based on T-reg pharmacodynamic findings and overall benefit-risk profile, the 24 µg/kg every two weeks induction dosing and monthly and quarterly maintenance dosing regimens have been selected for the ZENITH AD Phase 3 program, which is currently enrolling. Rezpegaldesleukin is currently in Phase 3 development. The registrational program in atopic dermatitis includes three global, randomized, double-blind, placebo-controlled trials: ZENITH AD-1 and ZENITH AD-2 initiated in July 2026, which are currently enrolling biologic and systemic JAK inhibitor treatment-naive patients, and ZENITH AD-3, which will enroll patients with prior systemic biologic and/or JAK inhibitor treatment experience when the study initiates in September 2026. In early 2027, a single registrational Phase 3 trial in alopecia areata is planned, based upon strong data from the randomized, placebo-controlled Phase 2b REZOLVE-AA study. In February 2025, the U.S. FDA granted Fast Track designation for rezpegaldesleukin for the treatment of adult and pediatric patients 12 years of age and older with moderate-to-severe atopic dermatitis whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable. In July 2025, the FDA granted Fast Track designation for rezpegaldesleukin for the treatment of severe alopecia areata in adults and pediatric patients 12 years of age and older who weigh at least 40 kg. Rezpegaldesleukin is being developed as a self-administered injection for a number of autoimmune and inflammatory diseases, including atopic dermatitis, alopecia areata and Type 1 diabetes. Rezpegaldesleukin targets the interleukin-2 receptor complex in the body to stimulate proliferation of powerful inhibitory immune cells known as regulatory T-cells. By activating these cells, rezpegaldesleukin may act to bring the immune system back into balance.
