A REZOLVE-AD Phase 2b trial conducted by Nektar Therapeutics on rezpegaldesleukin has revealed promising findings for treating mild to severe atopic dermatitis (AD). It is a novel immune-modulating treatment, and the initial 16-week phase of the global trial showed significant improvements in many efficacy endpoints. This indicates the potential of this drug as a first-in-class regulatory T-cell (Treg) stimulator.
Rezpegaldesleukin is an agonist of an interleukin-2 (IL-2) pathway, which specifically expands Tregs that play an important role in controlling inflammatory responses. This trial involved 393 randomized patients who received rezpegaldesleukin at high dose (24 µg/kg q2w), mild dose (18 µg/kg q2w), low dose (24 µg/kg q4w), or placebo. All three treatment groups met the primary endpoint, with a statistically significant percentage reduction in Eczema Area and Severity Index (EASI) at week 16, with a p < 0.001. It indicated a dosage-dependent enhancement: 53% for the low dosage, 58% for the mild dosage, and 61% for the high dosage, compared to 31% for the placebo.
This research also shows a rapid onset of therapeutic benefits. According to Dr. Jonathan Silverberg, the study suggests that rezpegaldesleukin can reduce symptoms more quickly compared to other immunomodulatory therapies, with no adverse effects such as oral herpes or conjunctivitis. He also highlighted that the Treg-based method is a unique therapeutic method in dermatology, which differentiates rezpegaldesleukin from other medications.
Translational biomarker analysis showed a dosage-dependent increase in circulating Tregs (6-fold increase in high dosage arm). This is followed by a significant decrease in main inflammatory mediators associated with Alzheimer’s disease (AD), like periostin, MDC/CCL22, TARC/CCL17, and IL-16. These findings suggest Treg expansion may help restore immune balance and reduce systemic inflammation in AD.
The safety profile was consistent with the previous studies and showed good tolerability. Injection site reactions (ISRs) were the most common adverse effects, which were seen in 69.7% of treated patients, but they were all mild and self-resolving. Severe ISRs occurred in only 0.2% of patients. Other commonly reported adverse effects in treatment arms (versus placebo) involved pyrexia (6.3% vs. 2.7%), headache (6.3% vs. 4.1%), and eosinophilia (7.8% vs. 2.7%). Severe adverse effects (SAEs) were rare, with 1.6% of the drug-treated patients. Importantly, no increase in infectious disease or mucosal complications was reported.
The REZOLVE-AD trial started in October 2023 and recruited patients from over 100 sites worldwide, mainly in Europe, with additional sites in Australia and North America. The inclusion criteria included an EASI score of 16, a vIGA-AD score of 3 or higher, and involvement of 10% or more of the body surface area (BSA).
Nektar plans to present full results at an upcoming medical conference and expects long-term maintenance results from this trial in early 2026. Furthermore, top-line data from a similar Phase 2b trial (REZOLVE-AA) of rezpegaldesleukin in patients with severe alopecia areata are expected in Q4 2025.
The FDA has granted Rezpegaldesleukin Fast Track designation to treat mild-to-severe AD in patients aged 12 and older who are refractory to topical treatments. It is also being investigated as a self-injectable treatment for various autoimmune and inflammatory disorders.
Rezpegaldesleukin is positioned as a key component of Nektar Therapeutics’ immunology strategy. Along with this, the company is working on the clinical and preclinical development of various immune-modulating medicines, including the IL-15 receptor agonist NKTR-255 and TNFR2-targeting antibodies for cancer immunotherapy.
In conclusion, the REZOLVE-AD Phase 2b study demonstrates that rezpegaldesleukin is a fast-acting, potent, and well-tolerated new therapeutic option for patients with mild to severe atopic dermatitis, supporting its potential for broader application and further clinical development in immune-mediated diseases.
Reference: Nektar Therapeutics. 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. Accessed June 25, 2025. REZOLVE-AD Phase 2b Study of Rezpegaldesleukin Meets Primary and Key Secondary Endpoints in Patients with Moderate-to-Severe Atopic Dermatitis
