FDA Grants Rezpegaldesleukin Fast Track Designation for Treatment of Children, Adults With Atopic Dermatitis

Rezpegaldesleukin (Rezpeg; Nektar Therapeutics) has received fast track designation from the FDA for the treatment of adult and pediatric patients 12 years and older with moderate-to-severe atopic dermatitis (AD) whose disease is not adequately controlled with topical prescription therapies or when those therapies are not recommended. The decision was based on data from the RESOLVE-AD trial (NCT06136741), where rezpegaldesleukin yielded rapid, measurable improvements that persisted after ceasing treatment.¹

Depiction of regulatory T-cell activation | Image Credit: © Zuraara - stock.adobe.com

AD, or eczema, is an inflammatory disease that causes dry, itchy, inflamed skin and can occur in both children and adults. It is not contagious but can be a lifelong, chronic condition that greatly impacts an individual’s quality of life. AD can develop due to underlying gene variations that weaken the skin’s barrier function, which protects the skin from bacteria, irritants, allergens, and environmental factors. The weak skin barrier is believed to trigger an immune system response, which results in an inflammatory response.²

Regulatory T cells (Tregs) play a key role in immune suppression. In AD, severe cases often involve dysregulated T-cell responses, which can cause the immune system to attack itself, thereby damaging healthy cells. Rezpegaldesleukin is an investigational interleukin-2 receptor-targeting agent that may address the underlying immune system imbalances in patients with autoimmune or inflammatory conditions. Through a self-administered injection, rezpegaldesleukin is meant to stimulate proliferation and activation of Tregs to bring the immune system back into balance.^3,4

Rezpegaldesleukin demonstrated clinically meaningful results in the randomized, double-blind, parallel-group, placebo-controlled, phase 2b REZOLVE-AD study assessing 398 adult patients with moderate-to-severe AD who had not previously received treatment with biologic or Janus kinase (JAK) inhibitor therapies. They were randomized to 3 different dosing regimens of rezpegaldesleukin and placebo for a 16-week induction period, which was followed by re-randomization of patients who met the Eczema Area and Severity Index (EASI) score threshold to 1 of 2 maintenance regimens at their original dose level to receive maintenance therapy either once a month or once every 3 months.^1,4

The primary end point of the study was the mean improvement in EASI score at the end of the 16-week induction treatment period, with secondary endpoints of the proportion of patients achieving Validated Investigator Global Assessment of 0 or 1, those achieving EASI-75, and those achieving a greater than or equal to a 4-point improvement in the Itch Numeric Rating Scale.⁴

Patients receiving treatment with rezpegaldesleukin achieved rapid, measurable improvements to exploratory disease outcomes during a 12-week induction treatment phase and for at least 36 weeks after stopping treatment.⁴

"We are pleased that rezpegaldesleukin has been designated a Fast Track product," Jonathan Zalevsky, PhD, senior vice president and chief research and development officer at Nektar, said in a press 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."⁴

REFERENCES

1. A phase 2b study to evaluate rezpegaldesleukin (Rezpeg) in the treatment of adult patients with moderate-to-severe atopic dermatitis (REZOLVE-AD). Updated January 28, 2025. Accessed February 10, 2025. https://clinicaltrials.gov/study/NCT06136741?intr=REZOLVE-AD&rank=1

2. Atopic dermatitis (eczema). Mayo Clinic. May 15, 2024. Accessed February 10, 2025. https://www.mayoclinic.org/diseases-conditions/atopic-dermatitis-eczema/symptoms-causes/syc-20353273

3. Agrawal R, Wismiewski J, Woodfolk J. The role of regulatory T cells in atopic dermatitis. Curr Probl Dermatol. August 14, 2015. doi: 10.1159/000323305

4. Nektar Therapeutics receives fast track designation for rezpegaldesleukin for the treatment of moderate-to-severe atopic dermatitis. Nektar. February 10, 2025. Accessed February 10, 2025. https://ir.nektar.com/news-releases/news-release-details/nektar-therapeutics-receives-fast-track-designation