By VETTAPHARMA reporter – Derek Roche: Nektar Therapeutics announced publication in The Lancet of positive 16-week induction results from the Phase 2b REZOLVE-AD study of rezpegaldesleukin in adults with moderate-to-severe atopic dermatitis.
The global, randomized, double-blind, placebo-controlled study enrolled 393 biologic- and JAK inhibitor-naive adults across 107 sites in 10 countries. Participants received one of three rezpegaldesleukin regimens—24 µg/kg every 2 weeks, 18 µg/kg every 2 weeks, or 24 µg/kg every 4 weeks—or placebo for 16 weeks.
All three rezpegaldesleukin regimens met the study’s primary endpoint, demonstrating statistically significant improvements in mean percentage reduction in Eczema Area and Severity Index (EASI) from baseline at Week 16. Reductions were 61%, 58%, and 53%, respectively, compared with 31% with placebo.
The 24 µg/kg every-2-weeks regimen also met key secondary endpoints, including EASI-75, EASI-90, Investigator Global Assessment for Atopic Dermatitis response, itch severity, and body surface area. EASI-75 response was achieved by 42% of patients versus 17% with placebo, while EASI-90 response was achieved by 25% versus 9%, respectively.
Patient-reported outcomes also favored rezpegaldesleukin, including improvements in quality of life, disease control, pain, and sleep. Efficacy was observed as early as Week 2 in the 24 µg/kg dose groups, with responses continuing to deepen through Week 16.
The treatment demonstrated a favorable safety profile, with serious adverse events reported in 2% of patients during the 16-week induction period. No deaths were reported, and Nektar reported no increased risk of infections, conjunctivitis, or other safety signals associated with currently approved atopic dermatitis therapies.
Rezpegaldesleukin is a regulatory T-cell stimulator designed to selectively stimulate regulatory T cells through the interleukin-2 receptor complex. By increasing regulatory T cells, the therapy is intended to restore immune balance rather than broadly suppress the immune system.
Biomarker findings supported this proposed mechanism, with dose-dependent reductions in several atopic dermatitis biomarkers, including TARC/CCL17, periostin, MDC/CCL22, and interleukin-19.
Based on the Phase 2b findings, 24 µg/kg every 2 weeks has been selected as the induction regimen for Nektar’s ongoing Phase 3 ZENITH AD program, alongside monthly and quarterly maintenance regimens. ZENITH AD-1 and ZENITH AD-2 began enrolling in July 2026, while ZENITH AD-3 is planned to evaluate patients with prior systemic biologic and/or JAK inhibitor treatment experience.
Quick FAQs
1. What Is Rezpegaldesleukin?
Rezpegaldesleukin is an investigational regulatory T-cell stimulator designed to activate regulatory T cells through the interleukin-2 receptor complex and restore immune balance.
2. What Happened?
Nektar Therapeutics announced publication of positive Phase 2b REZOLVE-AD 16-week induction results in The Lancet.
3. What Were The Key Results?
All three dosing regimens met the primary endpoint. The 24 µg/kg every-2-weeks regimen produced a 61% mean reduction in EASI versus 31% with placebo at Week 16.
4. What Other Outcomes Improved?
The 24 µg/kg every-2-weeks regimen improved EASI-75, EASI-90, investigator-assessed disease response, itch, body surface area, quality of life, disease control, pain, and sleep compared with placebo.
5. What Was The Safety Profile?
Serious adverse events occurred in 2% of patients, with no deaths during the 16-week induction period. No increased risk of infections or conjunctivitis was reported.
6. What Happens Next?
Nektar is advancing rezpegaldesleukin into the Phase 3 ZENITH AD program, with the 24 µg/kg every-2-weeks regimen selected for induction.
