REZOLVE-AD: Rezpegaldesleukin Shows Consistent Efficacy Across Atopic Dermatitis Severity, With Raj Chovatiya, MD, PhD

Rezpegaldesleukin (Nektar Therapeutics), novel IL-2 receptor agonist targeting regulatory T cells has demonstrated dose-dependent, statistically significant improvements in atopic dermatitis outcomes across both moderate and severe disease — with consistent responses observed regardless of baseline severity, geographic region, or asthma comorbidity status.1

These findings are from the phase 2b REZOLVE-AD study (NCT06136741) presented at the 2026 American Academy of Dermatology (AAD) Annual Meeting held in Denver, Colorado, from March 27-31, by Raj Chovatiya, MD, PhD, MSCI, FAAD, Associate Professor at Rosalind Franklin University of Medicine and Science Chicago Medical School and Founder and Director of the Center for Medical Dermatology and Immunology Research in Chicago.

HCPLive spoke with Chovatiya to learn more about REZOLVE-AD, which enrolled 393 patients with moderate-to-severe atopic dermatitis not previously treated with a JAK inhibitor or biologic. Participants were randomized 3:3:3:2 to rezpegaldesleukin 24 µg/kg every 2 weeks (n = 104), 18 µg/kg every 2 weeks (n = 106), 24 µg/kg every 4 weeks (n = 110), or placebo every 2 weeks (n = 73) over a 16-week induction period. Chovatiya described the mechanism as fundamentally distinct from existing approved therapies — rather than blocking active inflammation downstream, rezpegaldesleukin expands and activates Tregs via preferential binding to the IL-2 receptor complex, targeting the resolution phase of immune dysregulation.1

On the primary endpoint of mean percent EASI reduction at week 16, the 24 µg/kg q2w arm achieved 61% improvement versus 31% for placebo (P <.001), with the 18 µg/kg q2w and 24 µg/kg q4w arms achieving 58% (P <.001) and 53% (P <.001), respectively — demonstrating clear dose-dependence. The finding that most engaged Chovatiya was the consistency across baseline disease severity: in patients with moderate disease (vIGA = 3), EASI improvements were 59%, 58%, and 54% across the three active arms versus 32% for placebo; in patients with severe disease (vIGA = 4), improvements were 63%, 58%, and 50% versus 29% — nearly identical trends suggesting baseline severity did not meaningfully modulate treatment response. EASI-75 and EASI-90 response rates showed the same pattern across both moderate and severe subgroups. A forest plot analysis of EASI-75 response for the 24 µg/kg q2w arm further confirmed consistent treatment effect across baseline EASI above and below 21, geographic region, and presence or absence of asthma comorbidity — all favoring rezpegaldesleukin over placebo.1

On safety, injection site reactions occurred in 69.7% of all rezpegaldesleukin-treated patients versus 4.1% for placebo, nearly all mild-to-moderate; other TEAEs occurring at ≥5% frequency included eosinophilia (7.8% vs. 2.7%), pyrexia (6.3% vs. 2.7%), headache (6.3% vs. 4.1%), upper respiratory tract infections (5.9% vs. 5.5%), and arthralgia (5.0% vs. 1.4%), with no increased risk of conjunctivitis, oral ulcers, malignancy, or infections including oral herpes. The phase 3 ZENITH-AD program is in final planning with initiation expected in Q2 2026, with Chovatiya noting that the Treg-modulating mechanism raises the prospect of extended dosing intervals or treatment breaks — a meaningfully different proposition from the continuous cytokine inhibition model that defines the current standard of care.1

“One of the exciting things about rezpeg is that it may potentially allow for... extended dosing intervals [and] potentially breaks off therapy, given that it's modulating a regulatory T cell, as opposed to inhibiting an activated T cell. So this is really what next phase of studies is going to be designed to test,” Chovatiya said.

Nektar Therapeutics also presented late breaking data on rezpegaldesleukin in alopecia areata, from the phase 2b REZOLVE-AA study (NCT06340360).2 HCPLive also caught up with that presenter David Rosmarin, MD, Chair of the Department of Dermatology and Associate Professor of Dermatology at Indiana University School of Medicine in Indianapolis, during the meeting. Watch the conversation here.

Chovatiya previously reported serving as an advisor, consultant, speaker, and/or investigator for AbbVie, Amgen, Apogee Therapeutics, Arcutis, Argenx, ASLAN Pharmaceuticals, Beiersdorf, Boehringer Ingelheim, Bristol Myers Squibb, Cara Therapeutics, Dermavant, Eli Lilly and Company, FIDE, Formation Bio, Galderma, Genentech, GSK, Incyte, LEO Pharma, L’Oréal, Nektar Therapeutics, Novartis, Opsidio, Pfizer Inc., Regeneron, RAPT, Sanofi, Sitryx, and UCB.

References

1. Silverberg JI, Bieber T, Chovatiya R, et al. Novel regulatory T-cell enhancing biologic rezpegaldesleukin: phase 2b efficacy, safety, and baseline severity–dependent treatment response in moderate-to-severe atopic dermatitis. Presented at: American Academy of Dermatology Annual Meeting; March 27–31, 2026; Denver, CO. Poster #73858