Rezpegaldesleukin Demonstrates Long-Term Efficacy in Atopic Dermatitis Trial
Nektar Therapeutics Reports Promising Long-Term Outcomes for Rezpegaldesleukin in Atopic Dermatitis
Nektar Therapeutics has unveiled encouraging long-term efficacy and safety findings from the 36-week blinded maintenance phase of the 52-week Phase 2b REZOLVE-AD study. This trial evaluated the effects of rezpegaldesleukin in patients suffering from moderate-to-severe atopic dermatitis (AD). The results indicate sustained disease control with both monthly and quarterly maintenance dosing, paving the way for this pioneering regulatory T-cell (Treg) biologic to advance into a pivotal Phase 3 development program.
Trial Design
The REZOLVE-AD study is a global, randomized trial that enrolled a total of 393 patients with moderate-to-severe AD at around 110 sites worldwide. Initial findings were shared in June 2025. Following a 16-week induction period where participants received subcutaneous rezpegaldesleukin or a placebo, those who achieved at least a 50% improvement in the Eczema Area and Severity Index (EASI-50) were re-randomized to receive blinded maintenance therapy. This therapy involved administering the same induction dose either monthly (every 4 weeks) or quarterly (every 12 weeks) up to week 52.
Maintenance Results
The results from the maintenance phase demonstrated sustained and clinically relevant improvements across several critical efficacy endpoints. These included EASI-75, EASI-90, complete skin clearance (EASI-100), the validated Investigator Global Assessment for AD (vIGA-AD 0/1), and itch severity as measured by the Itch Numerical Rating Scale (NRS).
Among patients receiving 24 µg/kg of 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 sustained in 85% of patients on monthly dosing and 63% on quarterly dosing.
High rates of maintenance were also noted for EASI-90 and itch response, showcasing durable disease control across both physician-assessed and patient-reported outcomes. Notably, a significant proportion of patients experienced new or enhanced responses during the extended treatment period.
Additionally, several patients transitioned to EASI-75, EASI-90, vIGA-AD 0/1, and itch response from weeks 16 to 52. This suggests that ongoing Treg modulation may facilitate progressive improvement over time rather than a plateauing effect.
During the maintenance phase, a noteworthy two- to five-fold increase in EASI-100 response rates was observed among the 24 µg/kg dosing groups. Among all re-randomized patients, those on monthly dosing saw EASI-100 responses climb from 4% at week 16 to 22% at week 52, while quarterly dosing increased responses from 9% to 18%.
For patients who had already achieved robust responses at the maintenance baseline (EASI-75 or vIGA-AD 0/1), EASI-100 rates increased to 30% with monthly dosing and 27% with quarterly dosing. Dr. Jonathan Silverberg, MD, PhD, MPH, a Professor of Dermatology at The George Washington University School of Medicine and Health Sciences in Washington, DC, remarked, “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.”
“With both monthly and quarterly maintenance dosing, new and sustained responses were observed across the key endpoints of EASI-75, vIGA-AD 0/1, and itch, with a large proportion of patients achieving complete clearance with EASI-100.”
Safety and Next Steps
The safety profile of rezpegaldesleukin during the maintenance period was favorable and consistent with earlier reports from the induction phase.
No new safety signals emerged during the 36-week maintenance and escape phases. The overall discontinuation rate due to adverse events was low, at just 3.5%. Treatment-emergent adverse events were reported in 72% of re-randomized patients treated with rezpegaldesleukin, with most cases being mild or moderate in severity.
Injection site reactions were the most frequently reported adverse event. These reactions were primarily mild, occurred less often than during the induction phase, and rarely resulted in treatment discontinuation. Importantly, investigators noted the absence of increased risks commonly associated with other AD treatment mechanisms, such as conjunctivitis, oral herpes, oral ulcers, or malignancies.
Rezpegaldesleukin is a novel biologic that selectively stimulates regulatory T cells by targeting the interleukin-2 receptor complex, thereby restoring immune tolerance without broadly suppressing immune functions.
The durability of response observed with infrequent maintenance dosing supports the hypothesis that Treg expansion and functional enhancement could yield enduring disease modification in AD. In recognition of its potential, rezpegaldesleukin received fast track designation from the US Food and Drug Administration (FDA) in February of last year.
Howard W. Robin, President and CEO of Nektar Therapeutics, stated, “These new REZOLVE-AD study results reinforce the promise of the Treg mechanism to treat atopic dermatitis. The combined data from induction and maintenance now showcase the potential of a Treg biologic to offer compelling efficacy and safety advantages, along with less frequent maintenance dosing compared to existing treatments. We look forward to advancing to Phase 3 studies quickly, aiming to submit a Biologics License Application (BLA) by 2029.”
For those passionate about atopic dermatitis, we invite you to join us at the Revolutionizing Atopic Dermatitis (RAD) Conference 2026 in Nashville, taking place from June 17-19!
Sources
- Nektar Therapeutics press release, 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, Published February 10, 2026.
- Nektar Therapeutics press release, REZOLVE-AD Phase 2b Study of Rezpegaldesleukin Meets Primary and Key Secondary Endpoints in Patients with Moderate-to-Severe Atopic Dermatitis, Published June 24, 2025.
- Nektar Therapeutics press release, Nektar Therapeutics receives fast track designation for rezpegaldesleukin for the treatment of moderate-to-severe atopic dermatitis, Published February 10, 2025.