Rezpegaldesleukin Shows Promise in Alopecia Areata in Phase 2b Trial

Key Takeaways

• Rezpegaldesleukin demonstrated significant improvements in hair regrowth vs placebo in severe-to-very-severe alopecia areata (AA) through 36 weeks.
• Responses were dose-dependent and continued to increase over time, with no clear plateau observed.
• The therapy was well tolerated, with injection-site reactions as the most common adverse event and no major safety signals identified.

Rezpegaldesleukin, an IL-2 pathway agonist designed to expand regulatory T cells (Tregs), demonstrated clinical efficacy and a favorable safety profile in patients with severe-to-very-severe alopecia areata (AA), according to Phase 2b REZOLVE-AA data presented by David Rosmarin, MD, at the American Academy of Dermatology (AAD) 2026 Annual Meeting.

The randomized, double-blind, placebo-controlled trial enrolled 92 adults with AA (Severity of Alopecia Tool [SALT] score ≥50) to receive rezpegaldesleukin at 24 μg/kg or 18 μg/kg every 2 weeks, or placebo, over 36 weeks. The primary endpoint was mean percent change from baseline in SALT score.

Rezpegaldesleukin demonstrated approximately a fivefold improvement over placebo in SALT score reduction. At Week 36, mean percent change from baseline was −29.6% (P = .049) for the 24 μg/kg dose and −30.4% (P = .042) for the 18 μg/kg dose, compared with −5.7% for placebo. Dr. Rosmarin noted that both doses achieved an approximately 30% change from baseline in SALT score, with statistical significance observed for the higher dose beginning at Week 12. 

Secondary endpoints showed dose-dependent improvements. At Week 36, SALT30 responses were achieved in 48.9% and 45.7% of patients in the higher and lower dose groups, respectively, compared with 19.1% for placebo. Deeper responses, including SALT20 and SALT10, were also observed, with continued gains over time.

“Patients have not yet plateaued at the week 36 time point,” Dr. Rosmarin said, suggesting the potential for further improvement with longer treatment duration. 

Additional findings included eyebrow and eyelash regrowth in approximately 15% of patients receiving the higher dose, compared with none in the placebo group.

Mechanistically, rezpegaldesleukin selectively expands Tregs without activating proinflammatory T cells.

“It helps stimulate the T-regulatory cells,” Dr. Rosmarin explained of the novel immunomodulatory approach in AA. 

The treatment was well tolerated. Injection-site reactions were the most common adverse event, occurring in approximately 90% of treated patients, though these were predominantly mild to moderate and did not lead to discontinuation. No increased risk of serious infections, malignancy, or major cardiovascular events was observed.