Nektar Therapeutics Completes Enrollment for Phase 2b REZOLVE-AD Trial of Rezpegaldesleukin

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Nektar Therapeutics announced today that it has successfully completed target enrollment for its phase 2b REZOLVE-AD study.¹

This trial will evaluate the efficacy and safety of rezpegaldesleukin, a first-in-class interleukin-2 receptor (IL-2R) agonist, in patients with moderate to severe atopic dermatitis (AD). Rezpegaldesleukin’s mechanism centers on the proliferation and activation of regulatory T cells (Tregs), which are critical for immune system balance.

Prior studies, including proof-of-concept phase 1b research presented at the 2023 EADV Congress, demonstrated its ability to dose-dependently enhance Treg activity, leading to measurable and sustained improvements in AD symptoms for up to 36 weeks post-treatment discontinuation.²

"We are grateful to the patients and physicians whose strong interest in this novel mechanism, together with the proof-of-concept clinical data, led to completing enrollment of the study in just 14 months," said Howard Robin, CEO of Nektar Therapeutics, in a news release.¹ "Less than 10% of the 30 million atopic dermatitis patients who can receive biologics in the US and Europe are currently receiving treatment and we believe that novel mechanisms are key to helping more patients with this chronic and serious skin disorder."

The REZOLVE-AD trial involves 396 patients across 110 global sites, including the US, Canada, Europe, and Australia. Notably, 67% of participants were recruited from European nations.

Eligible patients met specific criteria, including an Eczema Area and Severity Index (EASI) score ≥16, body surface area involvement ≥10%, and a Validated Investigator Global Assessment (vIGA-AD) score of ≥3. Importantly, participants were biologic- and Janus kinase inhibitor-naïve, representing a population with few established treatment options.

During the trial, patients were randomized into 3 dosing regimens of rezpegaldesleukin or placebo for a 16-week induction period. Those achieving prespecified EASI thresholds will advance to maintenance therapy, receiving either monthly or quarterly treatments at their original dose.

The trial’s primary endpoint measures average improvement in EASI score after the induction phase. Secondary endpoints include the proportion of patients achieving EASI-75, attainment of a vIGA-AD score of 0 or 1, and improvements in Itch Numeric Rating Scale scores.

Beyond AD, rezpegaldesleukin is under investigation for other autoimmune and inflammatory conditions. The REZOLVE-AA study evaluates its potential in treating alopecia areata, a severe and psychologically impactful disease.³

Topline data from the 16-week induction period are expected in the second quarter of 2025.

References

1. Nektar Therapeutics announces completion of target enrollment in REZOLVE-AD phase 2b clinical trial of rezpegaldesleukin in patients with moderate-to-severe atopic dermatitis. News release. Nektar Therapeutics. January 10, 2025. Accessed January 10, 2025.https://ir.nektar.com/news-releases/news-release-details/nektar-therapeutics-announces-completion-target-enrollment
2. Silverberg J, Rosmarin D, Chovatiya R, et al. Efficacy and safety of single agent rezpegaldesleukin, a selective regulatory T-cell-inducing interleukin-2 conjugate, in the treatment of atopic dermatitis: final results from a randomized phase 1b study. Presented at: 2023 EADV Congress; October 2023. Accessed January 10, 2025. https://www.nektar.com/wp-content/uploads/2023/11/KFAD_LBA_presentation_for_EADV_13Oct2023_Final.pdf
3. Nektar Therapeutics announces initiation of phase 2b clinical study evaluating rezpegaldesleukin in patients with severe to very severe alopecia areata. News release. PR Newswire. March 5, 2024. Accessed January 10, 2025. https://www.prnewswire.com/news-releases/nektar-therapeutics-announces-initiation-of-phase-2b-clinical-study-evaluating-rezpegaldesleukin-in-patients-with-severe-to-very-severe-alopecia-areata-302079957.html