Phase 2b Clinical Trial of Rezpegaldesleukin in Atopic Dermatitis Achieves Target Enrollment
Nektar Therapeutics announced the milestone in its clinical program to evaluate the IL-2 receptor agonist, a potential first-in-class treatment for the chronic condition.
Nektar Therapeutics announced on January 10, the completion of target enrollment for the REZOLVE-AD Phase 2b clinical trial evaluating rezpegaldesleukin, a potential first-in-class interleukin-2 receptor (IL-2R) agonist, in patients with moderate-to-severe atopic dermatitis (AD).1
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Rezpegaldesleukin is designed to selectively activate and expand regulatory T cells (Tregs), which play a critical role in restoring immune balance in autoimmune and inflammatory conditions.1 The mechanism of action has demonstrated promising clinical activity in prior studies, including rapid and durable improvements in measurable disease outcomes for at least 36 weeks post-treatment cessation in patients with moderate-to-severe AD, according to the Nektar announcement. Proof of concept efficacy and data on safety from a phase 1b study of rezpegaldesleukin in AD were presented in October 2023 at the Congress of the European Academy of Dermatology and Venereology.2
REZOLVE-AD (NCT06136741), initiated in October 2023, enrolled 396 adults (aged 18 years and older) with moderate-to-severe AD who were biologic- and JAK inhibitor-naïve. Participants were randomly assigned to 1 of 3 dosing regimens of intravenously administered rezpegaldesleukin or placebo for a 16-week induction period. Participants achieving a prespecified threshold on the Eczema Area and Severity Index (EASI) at conclusion of the induction phase are re-randomized to maintenance regimens at their original dose level, receiving therapy either monthly or every 3 months.1
The study's primary endpoint is the mean change in EASI score at the end of the 16-week induction period. Secondary endpoints include:
- Proportion of patients at week 16 achieving a Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) score of 0 or 1 and at least a 2-point reduction from baseline
- Proportion achieving EASI-75 (improvement in EASI score of 75% or greater) and EASI-50
- Proportion achieving a 4 point or greater improvement on the Itch Numeric Rating Scale (NRS)
Patients were recruited from 110 sites globally, with 67% enrolled in European countries, 17% in the United States, 11% in Canada, and 5% in Australia. Inclusion criteria required a minimum baseline EASI score of 16.0, body surface area (BSA) involvement of at least 10%, and a vIGA-AD score of 3 or higher. Patients with unstable disease during screening were excluded.1
Howard W. Robin, Nektar’s CEO, highlighted the unmet need in AD treatment, noting that fewer than 10% of the estimated 30 million people with AD in the US and Europe currently receive biologics.3 “We believe that novel mechanisms like rezpegaldesleukin are key to helping more patients with this chronic and serious skin disorder,” Robin said in the company press release. Topline data from the induction period are expected in the second quarter of 2025.1
Rezpegaldesleukin is being evaluated as a self-administered injection for several autoimmune and inflammatory conditions, including in the REZOLVE-AA Phase 2b study for treatment of severe-to-very-severe alopecia areata (NCT06340360).
