REZOLVE-AA: Phase 2b Data Released on Rezpegaldesleukin for Alopecia Areata

New topline, phase 2b findings have been released on investigational rezpegaldesleukin, demonstrating a meaningful level of clinical effect in patients with severe-to-very-severe alopecia areata.1

The December 16 announcement by Nektar Therapeutics resulted from the conclusion of the 36-week induction treatment period of the phase 2b REZOLVE-AA trial assessing investigational rezpegaldesleukin, designed as a first-in-class interleukin (IL)-2 pathway agonist and regulatory T-cell (Treg) proliferator.

“With strong and differentiated clinical efficacy data already established in atopic dermatitis and comorbid asthma for this first-in-class Treg mechanism, these results provide a compelling proof-of-concept for rezpegaldesleukin in a second inflammatory skin disease," Jonathan Silverberg, MD, PhD, MPH, professor of dermatology at The George Washington University School of Medicine and Health Sciences, said in a statement.1

Alopecia areata is an autoimmune hair loss disease affecting an estimated 6.7 million individuals in the US and 160 million worldwide.2 As current treatments are commonly ineffective or marked by high relapse rates, a notable unmet need was described in Nektar’s release for more durable, effective medications. REZOLVE-AA is a global study conducted to assess rezpegaldesleukin as a potential alternative.

This phase 2b analysis, conducted in 92 patients with severe-to-very-severe alopecia areata. Patients were randomized (3:3:2) to receive one of two rezpegaldesleukin doses or placebo, administered as a subcutaneous injection twice-monthly. REZOLVE-AA’s primary endpoint was determined to be the mean percentage reduction at 36 weeks from the point of baseline in participants’ Severity of Alopecia Tool (SALT) scores.

After completing 36 weeks of therapy, participants who showed evidence of hair regrowth but had not achieved a SALT score greater than 20 were eligible to remain on treatment for an additional 16 weeks, continuing through Week 52 in a blinded extension phase. The primary and secondary efficacy outcomes, however, were formally evaluated at the conclusion of the initial 36-week induction period.

"As physicians, we have long been in search of an effective biologic for alopecia areata, given the safety limitations and prescribing burden of JAK inhibitors,” Silverberg noted in his statement.1 “Importantly, this is the first biologic to show a truly meaningful level of clinical effect in patients, which could expand the number of patients we can treat with this immune disorder."

The company highlighted both of the rezpegaldesleukin dose groups' production of more than a twofold improvement in SALT score reduction compared with those on placebo. The REZOLVE-AA investigative team found most participants beginning to show regrowth of their hair at the 16-week mark or later. While separation between the active treatment arms and placebo was noted at every assessed timepoint, the team found their primary endpoint did not attain conventional statistical significance in the overall analysis.

By Week 36, the investigators identified the mean percentage reduction in SALT score as 28.2% in the 24 µg/kg rezpegaldesleukin cohort and 30.3% in the 18 µg/kg cohort. This was compared with 11.2% in the placebo cohort, corresponding to P values of .186 and .121, respectively. Within the modified intent-to-treat population of 92 individuals, there were 4 individuals later identified as having major eligibility violations that should have precluded their randomization in REZOLVVE-AA.

When these subjects were excluded from the analysis, both of the rezpegaldesleukin dose arms achieved statistical significance for the study's primary endpoint. At the 36-week mark, mean SALT score reductions were shown to be 29.6% for the 24 µg/kg dose and 30.4% for those on 18 µg/kg, versus 5.7% for those on placebo, yielding P values of .049 and .042, respectively.

Notably, the investigative team noted the magnitude of benefit observed with rezpegaldesleukin stayed consistent regardless of whether these protocol violations were included. They noted a single placebo-treated patient with an eligibility violation accounted for a 5.5% difference in performance within the placebo arm.

Across the study's key secondary endpoints, including attainment of SALT scores of 30 or less, 20 or less, and 10 or less, as well as SALT30, both rezpegaldesleukin dosing levels demonstrated a dose-dependent clinical advantage relative to placebo. A plan was also noted by Nektar to submit the REZOLVE-AA findings for presentation at a medical conference in 2026. The data from these patients is ongoing in the 16-week treatment extension program, and it is slated to be available in early Q2 2026.1

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. https://ir.nektar.com/news-releases/news-release-details/rezolve-aa-phase-2b-study-rezpegaldesleukin-establishes-proof.

2. Lintzeri DA, Constantinou A, Blume-Peytavi U. Alopecia areata - Current understanding and management. J Dtsch Dermatol Ges. 2022 Jan;20(1):59-90. doi: 10.1111/ddg.14689. PMID: 35040577.