Nektar Therapeutics' rezpegaldesleukin, an investigational biologic therapy, has received Fast Track designation from the U.S. Food and Drug Administration (FDA) for the treatment of moderate-to-severe atopic dermatitis in adult and pediatric patients aged 12 years and older. This designation aims to expedite the development and review process for drugs addressing serious conditions with unmet medical needs.
Mechanism of Action
Rezpegaldesleukin targets the interleukin-2 receptor complex to stimulate the proliferation of regulatory T cells (Tregs). These cells play a crucial role in suppressing excessive immune responses, potentially restoring immune balance in patients with atopic dermatitis. Autoimmune and inflammatory diseases cause the immune system to mistakenly attack and damage healthy cells in a person's body. A failure of the body's self-tolerance mechanisms enables the formation of the pathogenic T lymphocytes that conduct this attack. By activating these cells, rezpegaldesleukin may act to bring the immune system back into balance.
Clinical Evidence and Trial Design
In patients with moderate-to-severe atopic dermatitis, rezpegaldesleukin has demonstrated rapid improvements in exploratory disease outcomes during a 12-week induction treatment phase, with benefits lasting for at least 36 weeks after treatment cessation. These findings were initially presented at the 2023 EADV Congress, showcasing proof-of-concept for this novel therapeutic approach.
The ongoing Phase 2b REZOLVE-AD study (NCT06136741) has enrolled 398 patients with moderate-to-severe atopic dermatitis who had not previously been treated with biologics or JAK inhibitors. Participants were randomized to receive one of three different dose regimens of rezpegaldesleukin or placebo for a 16-week induction period. Patients meeting a pre-specified Eczema Area and Severity Index (EASI) score threshold will be re-randomized to maintenance regimens at their original dose level, receiving therapy either once a month or once every three months.
The primary endpoint of the Phase 2b study is the mean improvement in EASI score at the end of the 16-week induction treatment period. Secondary endpoints include the proportion of patients achieving Validated Investigator Global Assessment (vIGA-AD) of 0 or 1, those achieving EASI-75 (75% improvement in EASI score), and those achieving a greater than or equal to a 4-point improvement in Itch Numeric Rating Scale (NRS).
Fast Track Designation Benefits
The FDA's Fast Track designation provides several advantages, including more frequent meetings and written interactions with the FDA to discuss the drug candidate's development plan. It also allows for potential eligibility for rolling review and priority review, which could expedite the approval process.
Jonathan Zalevsky, Ph.D., Senior Vice President and Chief Research & Development Officer at Nektar, stated, "Rezpegaldesleukin has the potential to address a significant unmet need for the millions of patients living with moderate-to-severe atopic dermatitis. 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."
Atopic Dermatitis Landscape
Atopic dermatitis, the most common form of eczema, affects approximately 30 million people in the United States. It is characterized by a defective skin barrier, leading to immune reactions and inflammation triggered by allergens and irritants. Current treatment options include topical therapies, biologics, and JAK inhibitors, but many patients still experience inadequate disease control.
Future Outlook
Nektar Therapeutics anticipates announcing topline data from the induction period of the Phase 2b REZOLVE-AD study in the second quarter of 2025. In addition to atopic dermatitis, rezpegaldesleukin is also being evaluated in a Phase 2b clinical trial for the treatment of severe-to-very-severe alopecia areata.
