REZOLVE-AD: Rezpegaldesleukin Improves Symptoms of Atopic Dermatitis

Positive results have been released from the 36-week blinded maintenance period of the 52-week REZOLVE-AD study of rezpegaldesleukin, a novel regulatory T-cell (Treg) biologic, in individuals with moderate-to-severe atopic dermatitis.1

These data, announced on February 10 by Nektar Therapeutics, resulted from the global, phase 2b REZOLVE-AD study, involving 393 individuals with atopic dermatitis. Atopic dermatitis is known to impact around 30 million patients in the US. The US Food and Drug Administration (FDA) granted a Fast Track designation for rezpegaldesleukin for the treatment of adult and pediatric patients aged 12 years and older with atopic dermatitis.2

"These data show that rezpegaldesleukin, as a broad-based Treg agonist, is emerging as one of the most important mechanisms in development to treat atopic dermatitis," Jonathan Silverberg, MD, PhD, MPH, professor of dermatology at The George Washington University School of Medicine and Health Sciences, said in a statement.1 "With both monthly and quarterly maintenance dosing, new and sustained responses were observed across the key endpoints of EASI-75, vIGA-0/1 and itch and with a large proportion of patients achieving complete clearance with EASI-100."

Investigators of the REZOLVE-AD study began in October 2023, conducting their research at roughly 110 sites around the world. Most of the participants involved in this analysis were treated in Europe (68%), followed by the US (16%), Canada (11%), and Australia (5%). Patients were required, in order to qualify for involvement, to have an Eczema Area and Severity Index (EASI) score of 16.0 at minimum, a validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) score of 3 or higher at both screening and randomization, and a level of body surface area involvement of 10% or greater.

There were 393 subjects involved in this global phase 2b study, with participants being randomized during the 16-week induction phase in a 3:3:3:2 ratio to be provided with 1 of 3 subcutaneous doses of rezpegaldesleukin or placebo. Rezpegaldesleukin-treated individuals who attained at least a 50% reduction in their 16-week EASI scores were re-randomized on a 1:1 basis to continue with the drug at their original induction dose administered either every 4 or every 12 weeks through Week 52 as part of a blinded maintenance period.

Those shown not to meet the EASI-50 threshold during induction entered a treatment escape arm that allowed up to 36 additional weeks of use. Both of the aforementioned maintenance schedules were linked with durable disease control. This was across multiple efficacy measures, including EASI-75, EASI-90, vIGA-AD response, and improvement on the Itch Numerical Rating Scale. The 24 µg/kg dose administered either monthly or quarterly demonstrated the strongest response maintenance by the 52-week mark.

Notably, continued treatment led to additional clinical gains, with a substantial number of patients achieving new EASI-75, EASI-90, itch, and vIGA-AD 0/1 responses by the end of the study, despite less frequent dosing. In the maintenance phase, the proportion of patients reaching complete skin clearance increased markedly. Among all re-randomized participants, EASI-100 response rates rose from 4% to 22% with Q4W dosing and from 9% to 18% with Q12W dosing between weeks 16 and 52.

Among those who already had an EASI-75 or vIGA-AD response at maintenance baseline, EASI-100 rates were found to have risen from 6% to 30% with monthly dosing and from 14% - 27% with quarterly dosing regimens. The team highlighted these rates as representing a 2- to 5-fold improvement in complete response rates for the 24 µg/kg regimens. The safety profile of rezpegaldesleukin during maintenance was consistent with earlier data from the induction period, with the investigators finding no new safety signals. Across all of those assessed, discontinuations resulting from AEs occurred in 3.5%.

Reports of treatment-emergent adverse events (TEAEs) were noted among 72% of re-randomized rezpegaldesleukin-treated individuals, 65% of placebo-treated patients in maintenance, and 83% of subjects in the escape cohort. Reactions at patients’ injection sites were the most often AEs reported, the majority of which were mild, occurred less frequently than during induction, and resulted in discontinuation of the drug in only .7% of those evaluated.

"These data highlight that rezpegaldesleukin offers a completely novel therapeutic modality for the potential treatment of atopic dermatitis with numerous advantages to existing classes," said David Rosmarin MC, the chair of the department of dermatology and associate professor of Dermatology at Indiana University School of Medicine, said in a statement.1

References

1. New REZOLVE-AD Maintenance Data in Atopic Dermatitis Demonstrate Rezpegaldesleukin Resulted in Durable and New Responses Across Key Disease Measurements with Both Monthly and Quarterly Dosing. Nektar Therapeutics. February 10, 2026. https://ir.nektar.com/news-releases/news-release-details/new-rezolve-ad-maintenance-data-atopic-dermatitis-demonstrate.

2. Smith T. FDA Grants Fast Track Designation to Rezpegaldesleukin for Atopic Dermatitis. HCPLive. February 10, 2025. Accessed February 10, 2026. https://www.hcplive.com/view/fda-grants-fast-track-designation-rezpegaldesleukin-atopic-dermatitis.