Efficacy and safety of the regulatory T cell-selective interleukin-2 receptor agonist rezpegaldesleukin (REZPEG) in the treatment of inflammatory skin diseases including atopic dermatitis

Abstract Regulatory T cell (Treg) impairment is implicated in the pathogenesis of chronic inflammatory diseases but relatively little is known about the therapeutic potential of Treg restoration. Here we present the first clinical evidence for the Treg-selective interleukin-2 (IL-2) receptor agonist rezpegaldesleukin (REZPEG) in two randomized, double-blind, placebo-controlled Phase 1b trials in patients with atopic dermatitis (AD) or psoriasis. REZPEG was safe and well-tolerated, demonstrating consistent pharmacokinetics and clinical efficacy, meeting the primary, secondary and exploratory objectives in both trials. AD patients receiving the highest dose tested demonstrated an 83% improvement in Eczema Area and Severity Index (EASI) score after 12 weeks of treatment. EASI improvement of ≥ 75% (EASI-75) and validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) responses were maintained for 36 weeks after treatment discontinuation in 71% and 80% of week 12 responders, respectively. These clinical improvements were accompanied by sustained increases in CD25bright Tregs and induction of multiple immunoregulatory mechanisms. REZPEG presents a novel homeostatic approach to cutaneous disease therapy and holds clinical potential in providing long-term, treatment-free disease control. ClinicalTrials.gov identifiers: NCT04081350 and NCT04119557.