Jonathan Zalevsky, PhD, on Rezpegaldesleukin’s Biologic Approach to Alopecia Areata

Jonathan Zalevsky, PhD, Chief Research and Development Officer at Nektar Therapeutics, met with Dermatology Times to discuss the clinical development of rezpegaldesleukin (REZPEG), an investigational interleukin-2 (IL-2) based therapy designed to selectively activate regulatory T cells (Tregs). This mechanism has shown potential for treating immune-mediated skin diseases such as atopic dermatitis and alopecia areata.

Zalevsky, who led the early development of rezpegaldesleukin, highlighted the recent Fast Track designation by the US Food and Drug Administration (FDA) for alopecia areata, an acknowledgment of the therapy’s potential to address significant unmet clinical needs. He emphasized that Fast Track status allows for more frequent interactions with the FDA and could accelerate the development and review process.

Unlike currently approved treatments for alopecia areata, like JAK inhibitors, rezpegaldesleukin offers a biologic approach with a novel mechanism that could provide sustained therapeutic benefits with potentially fewer side effects. JAK inhibitors, though effective, may be limited by tolerability concerns, especially for long-term use.

So far, rezpegaldesleukin has been evaluated in 9 clinical studies involving over 1,000 patients, including those with various autoimmune dermatologic conditions. In atopic dermatitis, rezpegaldesleukin showed promising results in a Phase 2b trial involving approximately 400 patients, and similar subcutaneous dosing regimens are now being tested in the ongoing Phase 2b REZOLVE-AA trial for alopecia areata.

The REZOLVE-AA trial targets patients with severe to very severe alopecia areata (SALT scores ≥50), including those with near-complete scalp involvement. Patients receive either 18 or 24 mcg/kg of rezpegaldesleukin subcutaneously twice monthly for 36 weeks, with an extension to 52 weeks for partial responders. The primary goal is hair regrowth and long-term disease control.

Zalevsky noted that rezpegaldesleukin may promote durable hair regrowth even after treatment cessation and this durability may be linked to Treg-mediated restoration of the hair cycle. With topline results expected in December, rezpegaldesleukin could become the first biologic approved for alopecia areata, offering a new therapeutic avenue grounded in immune modulation.

“Our goal with providing REZPEG as a treatment option is to help the patient on multiple avenues, both at reducing the inflammation that's causing the disease, but then also help the stem cells grow hair even more effectively,” Zalevsky said.