Nektar Reports Phase 2b Proof-of-Concept for Rezpegaldesleukin in Severe Alopecia Areata

Nektar Therapeutics has announced topline results from its Phase 2b REZOLVE-AA trial evaluating rezpegaldesleukin (REZPEG) in patients with severe-to-very-severe alopecia areata (AA). The data establish clinical proof of concept and support advancement into Phase 3 development, positioning rezpegaldesleukin as a potential non-JAK option for this autoimmune hair-loss condition.

What is Rezpegaldesleukin?

Rezpegaldesleukin is a first-in-class IL-2 receptor pathway agonist engineered to stimulate regulatory T cells (Tregs), rather than pro-inflammatory immune cells.

In alopecia areata, where autoreactive immune cells attack hair follicles, enhancing Treg activity is intended to dampen the pathological immune response and allow follicles to resume normal growth. This mechanism differs fundamentally from JAK inhibitors, which broadly block inflammatory signaling but carry well-documented safety and monitoring burdens.

Rezpegaldesleukin has already received FDA Fast Track designation for severe alopecia areata in patients aged 12 and older.

The REZOLVE-AA Trial

REZOLVE-AA is a global, randomized, double-blind, placebo-controlled Phase 2b study enrolling 92 patients with severe-to-very-severe alopecia areata (≥50% scalp involvement).

Design highlights:

• Randomization (3:3:2) to:
  • Rezpegaldesleukin 24 µg/kg
  • Rezpegaldesleukin 18 µg/kg
  • Placebo
• 36-week induction treatment period
• Optional 16-week blinded extension for responders
• Primary endpoint: mean percent reduction in Severity of Alopecia Tool (SALT) score at Week 36

Phase 2b Efficacy Results

Four patients were later identified as having major eligibility violations at baseline and excluded. Both rezpegaldesleukin dose arms demonstrated more than twice the hair regrowth effect seen with placebo. Mean SALT reductions are reported as: 

• 24 µg/kg: 29.6% (p=0.049)
• 18 µg/kg: 30.4% (p=0.042)
• Placebo: 5.7%

Most patients who responded began showing visible hair regrowth at Week 16 or later, which the company claims is consistent with immune-modulating rather than stimulatory mechanisms.

Secondary endpoints (not powered for significance) showed dose-dependent trends, including:

• SALT30 (30% improvement from the baseline) response rates approaching ~50% in treated patients
• Meaningful proportions achieving absolute SALT ≤30, ≤20, and ≤10
• Reported eyebrow and eyelash regrowth in some participants

Most patients who responded began showing visible hair regrowth at Week 16 or later, consistent with immune-modulating rather than stimulatory mechanisms.

Safety and Tolerability

Rezpegaldesleukin was well tolerated, with a safety profile consistent with prior studies:

• Nearly all treatment-emergent adverse events were mild to moderate and self-resolving
• Discontinuation due to adverse events: 1.4%
• No increased risk of serious infections, cardiovascular events, thrombosis, acne, or oral herpes compared with placebo
• Injection-site reactions were mostly mild, with no discontinuations due to ISRs

Importantly, no intensive laboratory monitoring requirements were reported, an advantage compared with existing systemic AA treatments.

What Comes Next?

Based on these results, Nektar plans to:

• Advance rezpegaldesleukin into Phase 3 trials for alopecia areata in 2026
• Leverage existing Fast Track designation to support regulatory interactions
• Present REZOLVE-AA data at a medical conference in 2026
• Report data from the 52-week extension cohort in early Q2 2026

Reflections

These topline results suggest rezpegaldesleukin may have meaningful activity in severe alopecia areata and support its advancement into Phase 3 development. The Treg-based mechanism and favorable safety profile are particularly encouraging in a treatment landscape dominated by broad immunosuppression. That said, conclusions remain premature without access to the full dataset. Details on methodlogy and the impact of reported eligibility exclusions will be essential for interpreting clinical relevance. 

Until full data are presented, rezpegaldesleukin should be viewed as a promising but still unproven investigational therapy.

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