An experimental biologic produced substantial improvements in adults with moderate-to-severe atopic dermatitis in a randomized phase 2b trial published in The Lancet.
The drug, rezpegaldesleukin, works differently from many newer eczema treatments. Rather than directly blocking a major inflammatory pathway, it is designed to selectively stimulate regulatory T cells (Tregs), immune cells that help restrain excessive immune responses.
After 16 weeks, average Eczema Area and Severity Index (EASI) scores fell by 53% to 61% across three rezpegaldesleukin regimens, compared with 31% with placebo. All three regimens met the study’s primary endpoint (Silverberg et al., 2026).
The results provide an encouraging efficacy signal. But this was a phase 2b trial in biologic-naive adults, injection-site reactions were extremely common, and long-term effectiveness and safety remain uncertain.
Rezpegaldesleukin is an investigational biologic being studied in adults with moderate-to-severe atopic dermatitis.
Key Takeaways
- REZOLVE-AD enrolled 398 adults, with 393 included in the reported analysis.
- Participants received one of three rezpegaldesleukin regimens or placebo for 16 weeks.
- Average EASI scores improved by 61%, 58%, and 53% with rezpegaldesleukin versus 31% with placebo.
- Rezpegaldesleukin is designed to stimulate regulatory T-cell activity rather than directly blocking inflammatory cytokines such as IL-4 or IL-13.
- Injection-site reactions occurred in 70% of treated participants versus 4% receiving placebo, although more than 99% were mild or moderate and resolved.
- No deaths occurred during the 16-week induction period.
- Nektar Therapeutics, the drug’s developer, funded the trial.
- The findings do not establish long-term safety, durability, or superiority to existing eczema treatments.
Why Is Rezpegaldesleukin Different?
Atopic dermatitis is a chronic inflammatory skin disease involving interactions between skin-barrier dysfunction and abnormal immune activity.
Several successful systemic treatments work by inhibiting inflammatory pathways. Rezpegaldesleukin, previously called NKTR-358, takes a different approach. It is an investigational interleukin-2 receptor agonist designed to preferentially stimulate regulatory T cells.
Tregs help maintain immune tolerance and restrain excessive immune responses. Preclinical research with NKTR-358 found selective effects on regulatory T-cell expansion and function (Dixit et al., 2021).
Early human research subsequently found dose-dependent, selective increases in Tregs in healthy volunteers and people with systemic lupus erythematosus (Fanton et al., 2022).
Phase 1b trials then provided preliminary evidence of rezpegaldesleukin activity in inflammatory skin diseases, including atopic dermatitis (Silverberg et al., 2024).
REZOLVE-AD was a substantially larger test of whether that biological strategy could translate into measurable improvement in eczema.
What Did the Phase 2b Trial Find?
REZOLVE-AD was an international, randomized, double-blind, placebo-controlled phase 2b trial conducted at 107 community research centers and hospitals across ten countries.
Adults had moderate-to-severe atopic dermatitis and had not previously received biologic treatment. Participants received rezpegaldesleukin at 24 μg/kg every two weeks, 18 μg/kg every two weeks, 24 μg/kg every four weeks, or placebo.
The primary endpoint was percentage change in EASI score at week 16.
- 61% with 24 μg/kg every two weeks
- 58% with 18 μg/kg every two weeks
- 53% with 24 μg/kg every four weeks
- 31% with placebo
All three active-treatment regimens produced statistically significant improvements compared with placebo.
What Does a 61% EASI Reduction Mean?
EASI is a clinical scoring system that measures the extent and severity of atopic dermatitis.
A 61% average reduction does not mean that 61% of patients had their eczema disappear. It means that the group’s average EASI score decreased by approximately 61% relative to baseline.
The placebo group also improved by 31%, which is why the placebo-adjusted difference matters. For the 24 μg/kg every-two-weeks regimen, the difference from placebo was approximately 30 percentage points.
That provides a more useful picture of the treatment effect than reporting the 61% reduction alone.
Is Rezpegaldesleukin Better Than Dupilumab?
The study cannot answer that question.
REZOLVE-AD compared rezpegaldesleukin with placebo, not dupilumab, lebrikizumab, tralokinumab, JAK inhibitors, or another systemic treatment.
Comparing response percentages across separate trials can be misleading because patient populations, baseline disease severity, background treatments, endpoints, and statistical methods can differ.
Rezpegaldesleukin also has not accumulated the large phase 3 and longer-term evidence base available for established treatments.
Its phase 2b results answer a narrower question: does this experimental treatment show enough efficacy and acceptable short-term safety to justify further development?
The results support that next step.
What Were the Side Effects?
Injection-site reactions were the most striking adverse event.
They occurred in 223 of 320 rezpegaldesleukin recipients, or 70%, compared with 3 of 73 placebo recipients, or 4%.
More than 99% of these reactions were mild or moderate and resolved.
Other adverse events occurring in at least 5% of treated participants and more frequently than placebo included eosinophilia, fever, headache, upper respiratory tract infection, and arthralgia.
No deaths occurred during the 16-week induction period, and investigators reported no evidence of increased serious or severe adverse events.
That does not establish long-term safety. Rare adverse events may become apparent only after substantially more people receive a drug or after longer exposure. Frequent injection-site reactions could also affect how acceptable a long-term injectable treatment is to patients.
Why Does the Biologic-Naive Population Matter?
The trial specifically studied adults who had not previously received biologic treatments for atopic dermatitis.
The results therefore do not establish how rezpegaldesleukin would perform in people whose eczema has failed to respond adequately to dupilumab or another biologic.
Nor do they establish where the drug would eventually fit into the treatment sequence if it reaches clinical practice. Those questions will require additional trials.
What Are the Important Limitations?
The study lasted 16 weeks, which is short relative to the potential duration of treatment for a chronic disease.
It did not compare rezpegaldesleukin directly with an established systemic treatment, and it does not establish the durability of improvement with continued treatment or after treatment stops.
Nektar Therapeutics funded the trial, and several study authors were affiliated with the company. Industry sponsorship is common in pharmaceutical development and does not invalidate the findings, but the relationship is relevant when interpreting evidence about an investigational drug.
There was also an unusual methodological detail. Data from two trial sites were excluded after those sites were closed for Good Clinical Practice non-compliance. According to the study report, both sites had been notified of closure approximately 300 days before database lock.
That does not by itself invalidate the remaining results, but it is relevant context.
What Does This Research Actually Tell Us?
REZOLVE-AD provides phase 2b evidence that rezpegaldesleukin has clinical activity in biologic-naive adults with moderate-to-severe atopic dermatitis.
All three dosing regimens produced significantly greater reductions in EASI scores than placebo after 16 weeks, with the largest average reduction, 61%, occurring with 24 μg/kg every two weeks.
The study is particularly interesting because rezpegaldesleukin represents a different immunological strategy. Instead of primarily blocking a specific inflammatory signal, it is designed to strengthen regulatory T-cell activity.
If that approach continues to show efficacy and acceptable safety in larger trials, it could support broader efforts to develop therapies aimed at restoring immune regulation.
But the distinction between promising drug candidate and proven treatment matters.
Rezpegaldesleukin has cleared an important phase 2b test. It has not yet answered the harder questions about long-term safety, durability, comparative effectiveness, or where it might eventually fit among established atopic dermatitis therapies.
For patients, those next studies will matter more than any single percentage from this trial.
References
Dixit, N., Fanton, C., Langowski, J. L., et al. (2021). NKTR-358: A novel regulatory T-cell stimulator that selectively stimulates expansion and suppressive function of regulatory T cells for the treatment of autoimmune and inflammatory diseases. Journal of Translational Autoimmunity, 4, 100103. https://doi.org/10.1016/j.jtauto.2021.100103
Fanton, C., Furie, R., Chindalore, V., et al. (2022). Selective expansion of regulatory T cells by NKTR-358 in healthy volunteers and patients with systemic lupus erythematosus. Journal of Translational Autoimmunity, 5, 100152. https://doi.org/10.1016/j.jtauto.2022.100152
Silverberg, J. I., Rosmarin, D., Chovatiya, R., et al. (2024). The regulatory T cell-selective interleukin-2 receptor agonist rezpegaldesleukin in the treatment of inflammatory skin diseases: Two randomized, double-blind, placebo-controlled phase 1b trials. Nature Communications, 15, 9230. https://doi.org/10.1038/s41467-024-53384-1
Silverberg, J. I., Rosmarin, D., Bieber, T., et al. (2026). Rezpegaldesleukin treatment of moderate-to-severe atopic dermatitis (REZOLVE-AD): Final results from the 16-week induction period of an international, double-blind, placebo-controlled, randomised phase 2b study. The Lancet, 408(10557), 833–846. https://doi.org/10.1016/S0140-6736(26)01143-8
