Rezpegaldesleukin Shows Promise in Treating Atopic Dermatitis and Psoriasis
核心洞察
Phase 1b studies reveal rezpegaldesleukin's efficacy, safety, and tolerability in patients with atopic dermatitis (搜索) and psoriasis (搜索).
The drug dose-dependently increased regulatory T cells and improved disease outcomes, with effects lasting at least 36 weeks post-treatment.
Biomarker analysis indicates rezpegaldesleukin modulates multiple immunoregulatory pathways, potentially attenuating Th1, Th2, and Th17 responses.
Nektar Therapeutics has announced the publication in Nature Communications of data from two Phase 1b studies, highlighting the potential of rezpegaldesleukin in treating atopic dermatitis (搜索) (AD) and psoriasis (搜索) (PsO). The studies demonstrated the drug's efficacy, safety, and tolerability in patients with these inflammatory skin conditions.
Rezpegaldesleukin, a first-in-class interleukin-2 receptor (搜索) (IL-2R) agonist, enhances the activity of regulatory T cells (Tregs). The Phase 1b trials showed that rezpegaldesleukin safely and dose-dependently increased Tregs and rapidly improved measurable exploratory disease outcomes that are largely durable for at least 36 weeks after ceasing treatment.
Clinical Validation of Treg Hypothesis
"These promising findings clinically validate, for the first time, the Treg hypothesis – that restoring Treg function through a central pathway of IL‑2R-driven Treg rescue can have disease remittive potential across a variety of chronic inflammatory skin diseases," said Jonathan Silverberg, M.D., Ph.D., Professor of Dermatology at George Washington University School of Medicine and lead study author. He added that rezpegaldesleukin can act on multiple disease-driving pathways and is uniquely poised to address a diversity of immunopathologies.
Key Findings from Phase 1b Studies
The Phase 1b trials were randomized, double-blind, placebo-controlled studies in patients with moderate-to-severe atopic dermatitis (搜索) (NCT04081350) or chronic plaque psoriasis (搜索) (NCT04119557). Participants received subcutaneous doses of 10 to 24 μg/kg of rezpegaldesleukin once every two weeks for 12 weeks.
- The drug was found to be safe and well-tolerated, meeting the primary and secondary objectives of each study.
- AD patients receiving high-dose rezpegaldesleukin demonstrated an 83% improvement in EASI score after 12 weeks of treatment.
- EASI-75 and vIGA-AD responses were maintained for 36 weeks after treatment discontinuation in 71% and 80% of week 12 responders, respectively.
- Clinical improvements were accompanied by sustained increases in CD25bright Tregs.
Immunoregulatory Mechanisms
Serum proteomic biomarkers demonstrated rezpegaldesleukin's ability to engage multiple immunoregulatory mechanisms to facilitate immune homeostasis. This may indicate a potential mechanism of attenuating Th1, Th2, and Th17 responses by restoring the balance of Tregs. The results also validate the role of IL-2-induced Treg proliferation and activation in the AD treatment paradigm, supporting the advancement of rezpegaldesleukin in the Phase 2b study in AD.
"The exciting clinical cross-indication efficacy here is buttressed by serum biomarker analysis demonstrating that rezpegaldesleukin can modulate multiple immunoregulatory pathways to provide rapid onset and duration of efficacy," said Jonathan Zalevsky, Ph.D., Chief Research & Development Officer at Nektar. He added that these findings further validate their therapeutic approach of using a Treg stimulator to dampen inflammatory responses and simultaneously restore immune balance in patients with chronic inflammatory skin diseases. Topline data from two Phase 2b rezpegaldesleukin studies in atopic dermatitis (搜索) and alopecia areata (搜索) are expected next year.
About Rezpegaldesleukin
Rezpegaldesleukin is a potential first-in-class resolution therapeutic that targets the interleukin-2 receptor (搜索) complex to stimulate the proliferation of regulatory T cells, aiming to restore immune system balance in autoimmune and inflammatory conditions. It is being developed as a self-administered injection and is wholly-owned by Nektar Therapeutics.