Rezpegaldesleukin met primary and key secondary endpoints at Week 16 in patients with moderate-to-severe atopic dermatitis (AD), according to the REZOLVE-AD Phase 2b study, which was presented at the 2025 European Academy of Dermatology and Venereology (EADV) Congress in Paris, France.

Rezpegaldesleukin (Nektar Therapeutics) is an interleukin (IL)-2 pathway agonist and regulatory T-cell (Treg) proliferator.

In the study, rezpegaldesleukin achieved statistical significance on the primary endpoint of mean improvement in Eczema Area and Severity Index (EASI) at Week 16 over baseline for all rezpegaldesleukin arms vs. placebo. Statistical significance at Week 16 was also achieved for key secondary endpoints measuring disease reduction in patients with moderate-to-severe AD, including EASI-75, EASI-90, Itch Numerical Rating Scale (NRS), Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD), and Body Surface Area (BSA), the study showed.

“These data from REZOLVE-AD presented today show a rapid onset of treatment effect for both clinician-assessed and patient-reported outcomes following the first few doses of rezpegaldesleukin,” says Jonathan Silverberg, MD, PhD, MPH, Professor of Dermatology at the George Washington University School of Medicine and Health Sciences and Director of Clinical Research and Contact Dermatitis, in Washington, DC, in a news release. “In addition, for the first time, we observe a deepening of clinical effect for patients with extended dosing of investigational therapy beyond 16 weeks, with a strengthening of absolute EASI reduction, along with higher EASI-75 and vIGA 0/1 response rates following 24 weeks of treatment.”

Highlights of the REZOLVE-AD Phase 2b Study:

Week 16 Efficacy

*N=63, 95, 92, and 102 for the placebo, 24 µg/kg q2w, 18 µg/kg q2w, and 24 µg/kg q4w arms; ns=not significant.

Key Patient-Reported Outcome Assessments

t*N=65, 100, 102, and 107 for the placebo, 24 µg/kg q2w, 18 µg/kg q2w, and 24 µg/kg q4w arms for DLQI; N=67, 101, 104 and 107 for ADCT; N=45, 71, 70 and 85 for ADSS Q1; and N=50, 84, 82 and 90 for Pain NRS; ns=not significant.

More About the REZOLVE-AD Study

The global Phase 2b REZOLVE-AD study randomized 393 patients with moderate-to-severe AD to receive subcutaneous treatment with three doses of rezpegaldesleukin: a high dose of 24µg/kg every two weeks (q2w), a middle dose of 18µg/kg every two weeks (q2w), and a low dose of 24µg/kg every four weeks (q4w), or placebo q2w.

Primary and secondary endpoints were assessed at Week 16. Following week 16, rezpegaldesleukin-treated patients who achieved EASI percent score reductions of >50 (EASI-50) were re-randomized (1:1) to continue at the same dose level on a q4w or q12w regimen through study week 52 in a blinded maintenance period. Placebo patients with EASI percent score reductions of ≥ 50% continue to receive placebo q4w.

The REZOLVE-AD study design allowed for patients who originally received placebo in the initial induction period and achieved less than EASI-50 at Week 16 to enter an open-label treatment escape arm to receive the high-dose rezpegaldesleukin regimen for a treatment period of up to 36 weeks.

The new included interim data is for 42 placebo patients who crossed over into the treatment escape arm. At the time of the data cut (August 18, 2025), 21 patients had reached 24 weeks of treatment with high-dose rezpegaldesleukin (24µg/kg q2w). Continuous treatment with rezpegaldesleukin demonstrated deepening of responses. For these patients, mean percent reduction in EASI at crossover Week 16 and at crossover week 24 were 68% and 75%, respectively. EASI-75 responses at crossover week 16 and crossover week 24 were 50% and 62%, respectively. Percent of patients with a vIGA-AD 0/1 response at crossover week 16 and crossover week 24 were 28% and 38%, respectively.

Safety Over 16-Week Induction Period