Rezpegaldesleukin (LY3471851) - (REZOLVE-AD)

July 21, 2026: Nektar Therapeutics (NASDAQ: NKTR) announced initiation of the first two global registrational Phase 3 trials (ZENITH AD-1 and ZENITH AD-2) evaluating rezpegaldesleukin in patients age 12+ with moderate-to-severe atopic dermatitis. The ZENITH AD program comprises three randomized, double-blind, placebo-controlled pivotal studies totaling ~1,530 patients: AD-1 and AD-2 (510 patients each) enroll systemic biologic/JAK inhibitor–naive patients; AD-3 (510 patients) enrolls treatment-experienced patients and is expected to begin in September.

Design: 24-week induction with 2:1 randomization to rezpegaldesleukin 24 mcg/kg vs placebo SC every two weeks; Week 24 responders (EASI-75 and/or IGA 0/1) enter a 28-week blinded maintenance re-randomization to monthly dosing, quarterly dosing, or placebo, while non-responders enter an open-label escape arm. Primary endpoint is IGA 0/1 at Week 24; key secondary includes EASI-75 at Week 24, plus EASI-90 and Itch-NRS (≥4-point reduction). Asthma control (ACQ-5) is prespecified for patients with baseline asthma history.

Initial Phase 3 topline data are expected mid-2028; BLA submission is targeted for 2029. The company also plans to initiate a single registrational Phase 3 trial in alopecia areata in early 2027 and expects initial Phase 2 Type 1 diabetes data in 2027. The AD and AA Phase 3 plans followed FDA End-of-Phase 2 meetings and EMA scientific advice; FDA Fast Track designations were noted for AD (Feb 2025) and severe alopecia areata (July 2025).