The regulatory T cell-selective interleukin-2 receptor agonist rezpegaldesleukin in the treatment of inflammatory skin diseases: two randomized, double-blind, placebo-controlled phase 1b trials

Jonathan I. Silverberg, David Rosmarin, Raj Chovatiya, Thomas Bieber, Stephen Schleicher, Lisa Beck, Melinda Gooderham, Sohail Chaudhry, Christie Fanton, Danni Yu, Joshua Levy, Yi Liu, Takahiro Miyazaki, Mary Tagliaferri, Carsten Schmitz, Ajay Nirula, Brian Kotzin and Jonathan Zalevsky ()
Additional contact information
Jonathan I. Silverberg: George Washington University School of Medicine
David Rosmarin: Indiana University School of Medicine
Raj Chovatiya: Rosalind Franklin University of Medicine and Science
Thomas Bieber: University Hospital
Stephen Schleicher: DermDox Centers for Dermatology
Lisa Beck: University of Rochester Medical Center
Melinda Gooderham: Queen’s University
Sohail Chaudhry: Nektar Therapeutics
Christie Fanton: Nektar Therapeutics
Danni Yu: Nektar Therapeutics
Joshua Levy: Levy Informatics LLC
Yi Liu: Nektar Therapeutics
Takahiro Miyazaki: Nektar Therapeutics
Mary Tagliaferri: Nektar Therapeutics
Carsten Schmitz: Eli Lilly and Company
Ajay Nirula: formerly affiliated with Eli Lilly and Company
Brian Kotzin: Nektar Therapeutics
Jonathan Zalevsky: Nektar Therapeutics

Nature Communications, 2024, vol. 15, issue 1, 1-19

Abstract: 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 clinical evidence for the Treg-selective interleukin-2 receptor agonist rezpegaldesleukin (REZPEG) in two randomized, double-blind, placebo-controlled Phase 1b trials in patients with moderate-to-severe atopic dermatitis (AD) (NCT04081350) or chronic plaque psoriasis (PsO) (NCT04119557). Key inclusion criteria for AD included an Eczema Area and Severity Index (EASI) score ≥ 16 and a validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) ≥ 3, and for PsO included a Psoriasis Area and Severity Index (PASI) score of ≥ 12 and a static Physician’s Global Assessment (sPGA) score of ≥ 3. REZPEG is safe and well-tolerated and demonstrates consistent pharmacokinetics in participants receiving subcutaneous doses of 10 to 12 µg/kg or 24 µg/kg once every 2 weeks for 12 weeks, meeting the primary and secondary objectives, respectively. AD patients receiving the higher dose demonstrate an 83% improvement in EASI score after 12 weeks of treatment. EASI improvement of ≥ 75% (EASI-75) and vIGA-AD responses are maintained for 36 weeks after treatment discontinuation in 71% and 80% of week 12 responders, respectively. These exploratory clinical improvements are accompanied by sustained increases in CD25bright Tregs. REZPEG thus represents a homeostatic approach to cutaneous disease therapy and holds clinical potential in providing long-term, treatment-free disease control.

Date: 2024
References: View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-53384-1 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-53384-1

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-53384-1

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().