Rezpegaldesleukin and Its Transformative Potential in Atopic Dermatitis: Insights from the REZOLVE-AD Trial

Amidst the intricate challenges of managing atopic dermatitis, rezpegaldesleukin emerges as a promising investigational option with early signals of efficacy for those affected by this persistent skin condition.

As dermatologists continually seek more effective treatments, ongoing trials such as REZOLVE-AD are pivotal, showcasing not just incremental findings but potentially meaningful advances—particularly via selective expansion of regulatory T cells and signals of durable disease control under study.

As an engineered IL‑2 variant designed to preferentially expand regulatory T cells (Tregs), it represents a mechanistically distinct approach. Rezpegaldesleukin's introduction into the therapeutic arena represents an exciting advancement in the field of dermatology; however, current AAD/EADV guidelines have not yet incorporated rezpegaldesleukin pending phase 3 results and regulatory approval. For context, the review on emerging atopic dermatitis therapies discusses the evolving treatment landscape rather than presenting direct data on rezpegaldesleukin.

The robust design of the REZOLVE-AD trial, a randomized, placebo-controlled, double-blind study, ensures that the data garnered on rezpegaldesleukin's efficacy is reliable and clinically relevant (trial identifier and primary endpoints reported by the sponsor; primary endpoint: proportion achieving EASI‑75 at prespecified timepoints). Notably, this discussion of methodological considerations in AD trials provides context on study design choices relevant to interpreting REZOLVE‑AD.

Clinical outcomes from the trial are particularly promising, with significant improvements noted in EASI-75 and vIGA-AD 0/1 scores; per the EADV 2025 presentation, reported responder rates improved through Week 24 in the analyzed cohort, reflecting statistically significant separation from placebo as summarized in conference materials. These measures capture clinician-assessed signs rather than quality of life; the EADV 2025 update primarily reported improvements in EASI-75 and vIGA-AD 0/1, with patient-reported outcomes to be interpreted as data mature.

Moreover, the implications for treatment protocols could be meaningful pending regulatory review, long‑term data, and guideline integration. The integration of rezpegaldesleukin into care pathways for patients with moderate-to-severe atopic dermatitis inadequately controlled with optimized topical therapy ± phototherapy could steer management toward more precision-based methods. In parallel with other individualized approaches in atopic dermatitis care (for example, phototherapy modalities such as full-body blue light), rezpegaldesleukin reflects the broader move toward more tailored, endotype-informed therapy. Any role in practice will depend on its safety profile, comparative effectiveness versus existing biologics and JAK inhibitors, and considerations of affordability and access.

Indeed, expert analyses of trial design and long-term outcomes in atopic dermatitis are essential to understanding durability, safety, and real-world benefit as evidence evolves.

Key Takeaways:

• REZOLVE-AD highlights early efficacy signals with a mechanistically distinct, Treg-selective approach under investigation.
• Clinician-assessed outcomes (EASI-75, vIGA-AD 0/1) have improved in interim reports, with further peer-reviewed data awaited.
• Potential clinical adoption will hinge on regulatory decisions, guideline updates, safety, comparative effectiveness, and access.