Rezpegaldesleukin Demonstrates Proof of Concept in Phase 2b Trial for Severe Alopecia Areata

Nektar Therapeutics reported topline results from the Phase 2b REZOLVE-AA trial showing that the investigational interleukin-2 pathway agonist rezpegaldesleukin produced greater reductions in scalp hair loss than placebo in participants with severe-to-very-severe alopecia areata, establishing proof of concept and supporting advancement to Phase 3 development.¹

REZOLVE-AA was a global, multicenter, randomized Phase 2b study enrolling 92 participants with severe-to-very-severe alopecia areata. Participants were randomized 3:3:2 to receive subcutaneous rezpegaldesleukin at 24 µg/kg, rezpegaldesleukin at 18 µg/kg, or placebo, administered twice monthly for 36 weeks. The primary endpoint was mean percentage reduction from baseline in the Severity of Alopecia Tool (SALT) score at Week 36.¹

At Week 36, the primary endpoint narrowly missed statistical significance in the modified intent-to-treat analysis, with mean SALT score reductions of 28.2% in the 24 µg/kg arm and 30.3% in the 18 µg/kg arm compared with 11.2% in the placebo group (P = .186 and P = .121, respectively). At all assessed time points, both rezpegaldesleukin dose arms separated from placebo.¹

Four of 92 participants were later identified as having major eligibility violations that should have excluded them from randomization. When these participants were excluded, both rezpegaldesleukin dose arms met statistical significance for the primary endpoint. Mean SALT score reductions at Week 36 were 29.6% for the 24 µg/kg arm and 30.4% for the 18 µg/kg arm versus 5.7% for placebo (P = .049 and P = .042, respectively). Investigators noted that the absolute treatment effect of rezpegaldesleukin was similar with or without exclusion of eligibility violations.¹

Key secondary endpoints favored rezpegaldesleukin, although the study was not powered to demonstrate statistical significance for these outcomes. The proportion of participants achieving a SALT ≥30% reduction from baseline was 48.9% in the 24 µg/kg group and 45.7% in the 18 µg/kg group, compared with 19.1% in the placebo group. Absolute SALT scores ≤30 were achieved by 29.0% and 21.9% of participants in the rezpegaldesleukin groups versus 8.4% with placebo.¹

Rezpegaldesleukin was generally well tolerated, with a safety profile consistent with prior studies. Nearly all treatment-emergent adverse events were mild to moderate and self-resolving. The discontinuation rate due to adverse events was 1.4% across the combined rezpegaldesleukin arms, and no participants discontinued treatment because of injection-site reactions. There was no increased risk of major adverse cardiovascular events, thrombosis, infection, acne, or oral herpes compared with placebo.¹

REZOLVE-AA (NCT06340360) enrolled participants across approximately 30 sites globally, with 62% of participants in Poland, 24% in Canada, and 14% in the United States. Participants had ≥50% scalp involvement at baseline, with enrollment of very severe disease capped at 25%. Participants demonstrating hair growth but not yet achieving SALT ≤20 after 36 weeks were eligible for a blinded 16-week extension through Week 52, with additional data expected in early Q2 2026.¹

Based on these results, Nektar plans to advance rezpegaldesleukin into a Phase 3 program for alopecia areata in 2026. The agent has received US Food and Drug Administration Fast Track designation for severe alopecia areata in adults and children aged 12 years and older who weigh at least 40 kg, as well as for moderate-to-severe atopic dermatitis.^1,2

Rezpegaldesleukin is an investigational therapy and is not approved for any indication. Its safety and efficacy have not been established by the US FDA.

References:

1. REZOLVE-AA Phase 2b Study of Rezpegaldesleukin Establishes Proof-of-Concept in Patients with Severe-to-Very-Severe Alopecia Areata. Nektar Therapeutics. December 16, 2025. Accessed December 17, 2025. https://ir.nektar.com/news-releases/news-release-details/rezolve-aa-phase-2b-study-rezpegaldesleukin-establishes-proof
2. Jennings S. FDA Grants Fast Track Designation to Rezpegaldesleukin for Alopecia Areata. Patient Care. July 31, 2025. Accessed December 17, 2025. https://www.patientcareonline.com/view/fda-grants-fast-track-designation-to-rezpegaldesleukin-for-alopecia-areata