Rezpegaldesleukin Shows Deepening Response and Long-Term Durability in 52-Week AD Trial

Nektar Therapeutics has reported positive long-term efficacy and safety results from the 36-week blinded maintenance period of the 52-week phase 2b REZOLVE-AD study evaluating rezpegaldesleukin in patients with moderate-to-severe atopic dermatitis (AD).¹ The findings demonstrate durable disease control with both monthly and quarterly maintenance dosing and support advancement of this first-in-class regulatory T-cell (Treg) biologic into a pivotal phase 3 development program.

Trial Design

REZOLVE-AD is a global, randomized trial that enrolled 393 patients with moderate-to-severe AD across approximately 110 sites worldwide. Initial data was shared in June of 2025.² Following a 16-week induction period, during which patients received subcutaneous rezpegaldesleukin or placebo, those achieving at least a 50% improvement in Eczema Area and Severity Index (EASI-50) were re-randomized to blinded maintenance therapy with the same induction dose administered either monthly (every 4 weeks) or quarterly (every 12 weeks) through week 52. The maintenance phase was designed to assess the durability of response, depth of efficacy over time, and the feasibility of less frequent dosing.

Maintenance Results

Results from the maintenance period showed sustained and clinically meaningful improvements across multiple key efficacy endpoints, including EASI-75, EASI-90, complete skin clearance (EASI-100), validated Investigator Global Assessment for AD (vIGA-AD 0/1), and itch severity measured by the Itch Numerical Rating Scale (NRS). Among patients receiving 24 µg/kg rezpegaldesleukin, 71% of those on monthly dosing and 83% of those on quarterly dosing maintained EASI-75 responses at Week 52. Similarly, vIGA-AD 0/1 responses were maintained in 85% and 63% of patients receiving monthly and quarterly dosing, respectively. High rates of maintenance were also observed for EASI-90 and itch response, indicating durable disease control across both physician-assessed and patient-reported outcomes.

Beyond maintenance of initial responses, a notable proportion of patients achieved new or deepened responses during the extended treatment period. Additional patients converted to EASI-75, EASI-90, vIGA-AD 0/1, and itch response between weeks 16 and 52, suggesting that continued Treg modulation may lead to progressive improvement over time rather than plateauing of effect. During maintenance, a two- to five-fold increase in EASI-100 response rates was observed in the 24 µg/kg dosing groups. Among all re-randomized patients, monthly dosing increased EASI-100 responses from 4% at week 16 to 22% at week 52, while quarterly dosing increased responses from 9% to 18%. In patients who already had robust responses at maintenance baseline (EASI-75 or vIGA-AD 0/1), EASI-100 rates rose to 30% with monthly dosing and 27% with quarterly dosing.

"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," said Jonathan Silverberg, MD, PhD, MPH, Professor of Dermatology at The George Washington University School of Medicine and Health Sciences in Washington, DC. "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."¹

Safety and Next Steps

The safety profile of rezpegaldesleukin during the maintenance period was favorable and consistent with prior reports from the induction phase. No new safety signals were identified during the 36-week maintenance and escape periods. The overall discontinuation rate due to adverse events was low at 3.5%. Treatment-emergent adverse events were reported in 72% of re-randomized rezpegaldesleukin-treated patients and were predominantly mild or moderate in severity. Injection site reactions were the most common adverse event. These were mostly mild, occurred less frequently than during induction, and rarely led to treatment discontinuation. Importantly, investigators highlighted the absence of increased risks commonly associated with other AD treatment mechanisms, including conjunctivitis, oral herpes, oral ulcers, or malignancies.

Rezpegaldesleukin is a novel biologic designed to selectively stimulate regulatory T cells through targeting the interleukin-2 receptor complex, thereby restoring immune tolerance rather than broadly suppressing immune pathways. The durability of response observed with infrequent maintenance dosing supports the hypothesis that Treg expansion and functional enhancement may offer sustained disease modification in AD. Rezpegaldesleukin was granted fast track designation by the US Food and Drug Administration (FDA) in February of last year.³

"These new REZOLVE-AD study results reinforce the promise of the Treg mechanism to treat atopic dermatitis," said Howard W. Robin, President and CEO of Nektar Therapeutics. "The combined data from induction and maintenance now showcase the potential of a Treg biologic to offer compelling efficacy and safety advantages and less frequent maintenance dosing as compared to current mechanisms. We look forward to advancing to Phase 3 studies quickly with the goal of submitting a BLA in 2029."¹

Passionate about atopic dermatitis? Come join us at the Revolutionizing Atopic Dermatitis (RAD) Conference 2026 in Nashville from June 17-19!

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. News release. Published February 10, 2026. Accessed February 10, 2026. https://ir.nektar.com/news-releases/news-release-details/new-rezolve-ad-maintenance-data-atopic-dermatitis-demonstrate

2. REZOLVE-AD Phase 2b Study of Rezpegaldesleukin Meets Primary and Key Secondary Endpoints in Patients with Moderate-to-Severe Atopic Dermatitis. News release. Nektar Therapeutics. Published June 24, 2025. Accessed February 10, 2025. https://ir.nektar.com/news-releases/news-release-details/rezolve-ad-phase-2b-study-rezpegaldesleukin-meets-primary-and

3. Nektar Therapeutics receives fast track designation for rezpegaldesleukin for the treatment of moderate-to-severe atopic dermatitis. News release. PRNewswire. Published February 10, 2025. Accessed February 10, 2026. https://www.prnewswire.com/news-releases/nektar-therapeutics-receives-fast-track-designation-for-rezpegaldesleukin-for-the-treatment-of-moderate-to-severe-atopic-dermatitis-302371995.html