DENVER — A novel biologic agent in development to treat alopecia areata (AA) emerged superior to placebo for efficacy and safety in a phase 2b study. Severity of Alopecia Tool (SALT) scores significantly decreased with treatment over 36 weeks with no plateau in treatment response observed. 

Rezpegaldesleukin, or “rezpeg,” binds to the interleukin-2 receptor and enhances regulatory T-cell activity without stimulating conventional T cells, a novel approach that “puts the brakes on the immune system,” David Rosmarin, MD, chair of the department of dermatology, Indiana University School of Medicine in Indianapolis, said during a late-breaker research session at the American Academy of Dermatology (AAD) 2026 Annual Meeting. 

Discovery of the role that regulatory T cells play in immunology, which is related to rezpegaldesleukin’s mechanism of action, received the 2025 Nobel Prize in Physiology or Medicine. 

Two Doses Compared to Placebo 

The Rezolve AA study included 92 adults with severe-to-very-severe AA at baseline (SALT scores ≥ 50), randomized 3:3:2 to receive higher or lower dose treatment or placebo.

A total 35 participants received 24 μg/kg rezpegaldesleukin, and 37 received 18 μg/kg rezpegaldesleukin — administered subcutaneously, twice a month — and 20 received a placebo. Their mean age was approximately 40 years, about two-thirds were female, and more than 80% of participants across groups were White. Patients were enrolled in Canada, Poland, and the United States.

Mean SALT scores ranged from 76 to 81 at baseline, mean duration of the current AA episode was about 2.5 to 3 years, and mean time since onset of AA ranged from 8 to 12 years across cohorts. The groups were well matched. “I would highlight, though, that the population receiving the high dose rezpegaldesleukin was a little bit more severe compared to placebo,” Rosmarin said, with baseline median SALT scores of 81 compared with 77 in the placebo group. 

The Rezolve-AA study also includes a blinded 16-week extension to characterize what happens when patients continue treatment with rezpegaldesleukin and a 24-week follow-up period after treatment to assess duration of response. These results will be presented in the future.

Higher Dose, Higher Efficacy 

The mean percent reduction in SALT at week 36 was the primary endpoint. Rosmarin and colleagues reported a mean decrease of 30% in SALT scores with both treatment doses vs a 6% decrease for those on placebo at 36 weeks (P < .05). This finding emerged from a modified intent-to-treat (ITT) analysis excluding four patients who violated major study eligibility criteria. 

Compared with placebo, “the highest dose of rezpeg is statistically significant, starting at week 12, and for every time point thereafter,” said Rosmarin, who is also associate professor of dermatology and the Kampen-Norins Scholar in Dermatology at Indiana University.

Secondary endpoints included changes in SALT 30, SALT 20, and SALT 10 scores. Modified ITT results showed that 29% of participants in the higher dose group achieved a SALT 30 score by week 36, as did 22% of those on the lower dose and 8% of the placebo cohort. The SALT 20 outcome was met by 16%, 15%, and 7% of participants in these groups, respectively. 

“And what we are happy to report, even though we don't have this full blinded extension data today, is that already there are three additional patients who have achieved the SALT 20 in the treatment extension,” Rosmarin said. In addition, seven patients who achieved SALT 30 are still on treatment, “suggesting more opportunities to capture patients with that endpoint,” he added.

The more stringent SALT 10 outcome (≤ 10% of the scalp affected by hair loss) was achieved by 12% of the higher dose rezpegaldesleukin group, 8% of the lower dose rezpegaldesleukin group , and 1% of the placebo group at 36 weeks in the modified ITT analysis. About 15% of patients achieved eyebrow and eyelash regrowth in the higher dose rezpegaldesleukin group compared with 7% in the lower dose group and none of the patients receiving placebo.

Injection Site Reactions Lead Adverse Events 

“Safety is perhaps the best aspect of rezpeg,” Rosmarin said. No increased risk of major adverse cardiac events, thrombosis, or serious infections was observed, for example.

A majority (92%) of participants receiving rezpegaldesleukin experienced an injection site reaction compared with 30% on placebo. Most were mild-to-moderate and tended to be redness, not pain or itch, Rosmarin said. There was only one severe injection site reaction, he added. 

A meeting attendee asked if the injection site reactions worsen with subsequent injections. “It's actually the opposite. We see the injection site reactions decrease over time,” Rosmarin replied.

There were five reports of eosinophilia in the higher dose group, compared with no cases in the lower dose or placebo groups. The eosinophilia was not clinically relevant, Rosmarin said. 

The safety profile of rezpegaldesleukin in Rezolve AA was consistent with findings across 11 studies with more than 1000 participants, and no new safety signal has emerged. 

“The lead indication for rezpeg is atopic dermatitis, and it's having a very favorable safety profile,” Rosmarin said. “We're not seeing signals for major cardiovascular events, malignancies, or serious infections. Furthermore, we're not seeing any lab changes beyond the eosinophilia.”

Future Steps 

Data from the Rezolve AA treatment extension to week 52 is planned for release in April 2026. In terms of efficacy, “the higher dose of rezpeg appears to be better,” and will be the dose evaluated in the phase 3 program, Rosmarin said.

In July 2025, the FDA granted Fast Track designation for rezpegaldesleukin for the treatment of severe AA in adults and children 12 years of age and older who weigh at least 40 kg.

“Overall, I’m very encouraged by this study that shows some early evidence of efficacy in the treatment of severe alopecia areata. We’re fortunate to have several approved treatments already available, but new treatments with different mechanisms of action are still needed,” said Benjamin Ungar, MD, director of the Alopecia Center of Excellence in the Department of Dermatology at Mount Sinai in New York City. 

“This study shows potential for this new approach to treating alopecia areata,” added Ungar, one of the study authors, told Medscape Medical News. “Although the results are promising, this is a relatively small preliminary study through 36 weeks of treatment,” he added. “Larger studies with longer-term follow up will be needed to more definitively demonstrate that this is a safe, effective treatment, and therefore a viable option for patients with alopecia areata.”

The study was sponsored by Nektar Therapeutics. Rosmarin disclosed he is a consultant for AbbVie, Abcuro, Ability Biologics, Almirall, AltruBio, Arena, Astria, Boehringer-Ingelheim, Bristol Myers Squibb, Celgene, Concert, CSL Behring, Dermavant, Dermira, Dualitas, Edesa Biotech, EMD Serono, Forte Biosciences, Incyte, Inmagene, Janssen, Kymera, Kyowa Kirin, Lilly, Nektar, Novartis, Pfizer, Phothera, RAPT, Regeneron, Recludix, Revolo Biotherapeutics, Sanofi, Sun Pharmaceuticals, Takeda, UCB, Viela Bio, and Zura Bio. He also receives research support from AbbVie, Amgen, Bristol Myers Squibb, Celgene, Dermira, Galderma, Incyte, Janssen, Lilly, Merck, Nektar, Novartis, Pfizer, RAPT, and Regeneron. He also is a paid speaker for AbbVie, Amgen, Bristol Myers Squibb, Celgene, Dermavant, Incyte, Janssen, Lilly, Novartis, Pfizer, Regeneron, and Sanofi.

Ungar disclosed serving as a consultant for AbbVie, Arcutis Biotherapeutics, Apogee Therapeutics, Bristol Myers Squibb, Botanix Pharmaceuticals, Castle Biosciences, Ebla Holdco, Fresenius Kabi, Galderma, Incyte, J&J, Leo Pharma, Lilly, Nektar Therapeutics, Pfizer, Primus Pharmaceuticals, Sanofi, Sun Pharma, UCB, Veradermics, and VRG Therapeutics.

Damian McNamara is a freelance contributor to Medscape Medical News. He worked full-time for Medscape and WebMD from 2018 to 2024. Damian has a BA in chemistry and an MA in science, health and environmental reporting/journalism.