First in Class Rezpegaldesleukin: Favorable Safety, Durable Responses in Alopecia Areata, With David Rosmarin, MD

Rezpegaldesleukin, a novel regulatory T-cell agonist, has demonstrated statistically significant hair regrowth in severe-to-very-severe alopecia areata, establishing proof of concept for what may become the first targeted biologic to receive an indication in a disease where JAK inhibitors have been the only approved advanced option.^1,2

The data, from the phase 2b REZOLVE-AA study (NCT06340360), were presented as a late-breaking oral presentation at the 2026 American Academy of Dermatology (AAD) Annual Meeting held in Denver, Colorado, from March 27-31, by David Rosmarin, MD, Chair of the Department of Dermatology and Associate Professor of Dermatology at Indiana University School of Medicine in Indianapolis. HCPLive spoke with Rosmarin during the meeting to learn more about the study, which enrolled 92 adults with severe-to-very-severe alopecia areata (SALT ≥50) who had not previously received a JAK inhibitor or biologic. Participants were randomized 3:3:2 to rezpegaldesleukin 18 µg/kg every two weeks (n = 37), 24 µg/kg every two weeks (n = 35), or placebo (n = 20) for 36 weeks, with stratification by baseline SALT ≥50 to <95 versus ≥95 to 100. Mean baseline SALT scores were 80.7, 76.3, and 76.6 across the 3 arms, respectively.¹

On the primary endpoint of mean percent SALT reduction at week 36, both active arms demonstrated approximately 30% mean reduction versus 6% for placebo — achieving statistical significance (P <.05) in a modified ITT analysis excluding 4 patients with major eligibility violations, with the 24 µg/kg dose showing statistically significant separation from placebo at every timepoint from week 12 through week 36.¹

In the secondary analyses, SALT ≤30 was achieved by 29.0% and 21.9% of patients in the 24 µg/kg and 18 µg/kg arms versus 8.4% for placebo; SALT ≤20 by 15.6% and 14.8% versus 6.7%; and SALT ≤10 by 11.5% and 8.3% versus 0.7%. Eyebrow and eyelash regrowth were also observed, with placebo-adjusted ClinRO response rates of 15% and 18% for eyebrows and eyelashes, respectively, in the 24 µg/kg arm.¹

Rosmarin emphasized that efficacy showed no plateau at week 36, a meaningful observation given the large number of partial responders still on treatment — and 16-week extension data expected in April 2026 may capture additional responders. The safety profile was consistent with over 1,000 patients exposed across 11 studies; the most common adverse events were mild-to-moderate injection site reactions (91.7% combined rezpegaldesleukin arms vs. 30.0% placebo) and eosinophilia (6.9% vs. 0%), with no increased rates of serious infections, MACE, thrombosis, or malignancy.¹

In our conversation, Rosmarin described the mechanistic rationale as genuinely differentiated — rezpegaldesleukin's selective pegylation allows preferential expansion of Tregs over effector T cells at therapeutic doses, a distinction that avoids the pro-inflammatory activity seen with native IL-2 at higher concentrations, and 1 recognized by the 2025 Nobel Prize in Physiology or Medicine. He noted that Nektar Therapeutics is planning a phase 3 program at the 24 µg/kg dose.

“I have high confidence that [the phase 3 study] will be positive and lead to ultimate FDA approval,” Rosmarin said.

Rosmarin’s disclosures include AbbVie, Abcuro, Ability Biologics, Almirall, AltruBio, Amgen, Arena, Astria, Boehringer-Ingelheim, Bristol Myers Squibb, Celgene, Concert, CSL Behring, Dermavant, Dermira, Dualitas, Edesa Biotech, EMD Serono, Forte Biosciences, Galderma, Incyte, Inmagene, Janssen, Kymera, Kyowa Kirin, Lilly, Merck, Nektar, Novartis, Pfizer, Phothera, RAPT, Recludix, Regeneron, Revolo Biotherapeutics, Sanofi, Sun Pharmaceuticals, Takeda, UCB, VielaBio, and Zura Bio.

References

1. Rosmarin D, Ungar B, Mesinkovska N, et al. Novel regulatory T-cell enhancing biologic rezpegaldesleukin: phase 2b efficacy and safety results following 36-weeks of therapy in severe-to-very-severe alopecia areata (REZOLVE-AA). Oral late-breaking presentation presented at: American Academy of Dermatology Annual Meeting; March 27–31, 2026; Denver, CO. Abstract 79863.

2. Nektar Therapeutics. Data from phase 2b REZOLVE-AD and REZOLVE-AA studies of rezpegaldesleukin presented at 2026 American Academy of Dermatology Annual Meeting. Press release. March 28, 2026. https://www.prnewswire.com/news-releases/data-from-phase-2b-rezolve-ad-and-rezolve-aa-studies-of-rezpegaldesleukin-presented-at-2026-american-academy-of-dermatology-annual-meeting-302727838.html. Accessed March 28, 2026.