Rezpegaldesleukin Receives Fast Track Designation for Moderate to Severe AD

Nektar Therapeutics recently announced that the FDA granted fast track designation to rezpegaldesleukin for the treatment of adult and pediatric patients aged 12 years and older with moderate to severe atopic dermatitis (AD) whose AD is not adequately controlled with topical therapeutics or when topicals are not recommended. Fast track designation is granted to investigational therapeutics that are designed to treat serious conditions and that have the potential to address unmet needs.¹

Rezpegaldesleukin is an investigational biologic therapy that targets the IL-2 receptor complex to stimulate the proliferation of regulatory T cells. According to Nektar, by activating regulatory T cells, rezpegaldesleukin may “act to bring the immune system back into balance.”

In a 12-week induction treatment phase and for at least 36 weeks after stopping treatment, rezpegaldesleukin rapidly improved measurable exploratory disease outcomes, demonstrating proof-of-concept for moderate to severe AD. The data presented at the 2023 EADV Congress confirmed rezpegaldesleukin’s ability to dose-dependently enhance regulatory T cell activity.²

"We are pleased that rezpegaldesleukin has been designated a Fast Track product," said Jonathan Zalevsky, PhD, senior vice president and chief research & development officer at Nektar, in the news release. "Rezpegaldesleukin has the potential to address a significant unmet need for the millions of patients living with moderate-to-severe atopic dermatitis. We remain on track to announce topline data from the induction period of our phase 2b REZOLVE-AD study in the second quarter of this year. This designation will now allow us to collaborate closely with the agency on the design of the registrational program for rezpegaldesleukin once we've completed phase 2."

The REZOLVE-AD (NCT06136741) study enrolled 398 patients with moderate to severe AD who had not previously received treatment with biologics or JAK inhibitors. Patients were randomized across 3 different dose regimens of rezpegaldesleukin and placebo for a 16-week induction treatment period. After the induction treatment period, patients who meet an Eczema Area and Severity Index (EASI) score threshold for advancement to maintenance will be re-randomized to 1 of 2 maintenance regimens at their original dose level to receive maintenance therapy either once a month or once every 3 months.

The primary end point of the phase 2b study is the mean improvement in EASI score at the end of the 16-week induction treatment period. Key secondary end points include the proportion of patients achieving a Validated Investigator Global Assessment (vIGA-AD) of 0 or 1, patients achieving EASI 75, and patients achieving a greater than or equal to a 4-point improvement in Itch Numeric Rating Scale. Enrollment criteria included a minimum EASI score of 16.0, a minimum Body Surface Area of 10%, and a minimum vIGA-AD of 3 at both screening and randomization.

REZOLVE-AD was initiated in October 2023 with patients enrolled in approximately 110 sites across the globe. Overall, 67% of patients were enrolled in Europe; 17% in the US; 11% in Canada; and 5% in Australia.

Beyond AD, rezpegaldesleukin is also being evaluated in the REZOLVE-AA study (NCT06340360), a randomized, double-blind, placebo-controlled phase 2b clinical trial for the treatment of patients with severe to very severe alopecia areata.

References

1. Nektar Therapeutics receives fast track designation for rezpegaldesleukin for the treatment of moderate-to-severe atopic dermatitis. News release. PRNewswire. February 10, 2025. Accessed February 10, 2025. https://www.prnewswire.com/news-releases/nektar-therapeutics-receives-fast-track-designation-for-rezpegaldesleukin-for-the-treatment-of-moderate-to-severe-atopic-dermatitis-302371995.html
2. Silverberg J, Rosmarin D, Chovatiya R, et al. Efficacy and safety of single agent rezpegaldesleukin, a selective regulatory T-cell-inducing interleukin-2 conjugate, in the treatment of atopic dermatitis: final results from a randomized phase 1b study. Presented at: 2023 EADV Congress; October 2023. Accessed February 10, 2025. https://www.nektar.com/wp-content/uploads/2023/11/KFAD_LBA_presentation_for_EADV_13Oct2023_Final.pdf