Rezpegaldesleukin is an investigational biologic medication in development for various autoimmune and chronic inflammatory conditions. This therapeutic agent addresses immune system imbalances, which contribute to these diseases. Rezpegaldesleukin represents an innovative approach to modulating immune responses, aiming to restore the body’s self-tolerance mechanisms often disrupted in autoimmune disorders.
How Rezpegaldesleukin Functions
Rezpegaldesleukin operates by targeting the interleukin-2 (IL-2) receptor complex on certain immune cells. Its primary action involves selectively stimulating the proliferation of regulatory T cells (Tregs). These Tregs are immune cells known for their ability to suppress other immune cells that contribute to inflammation and autoimmune responses.
By activating Tregs, rezpegaldesleukin aims to restore immune balance. This selective stimulation increases the number and function of these inhibitory immune cells without significantly stimulating cytotoxic CD8+ and CD4+ T cells, which often drive autoimmune disease. This re-establishes immune homeostasis, where the immune system distinguishes between healthy tissues and foreign invaders. This targeted approach provides more precise immune modulation than broader immunosuppressive therapies.
Conditions Targeted
Rezpegaldesleukin is being developed to treat a range of autoimmune and inflammatory conditions where an imbalance in the immune system is a contributing factor. A primary focus of its development is moderate-to-severe atopic dermatitis, a common form of eczema affecting approximately 30 million people in the United States. In atopic dermatitis, the immune system mistakenly triggers skin inflammation, causing itching, redness, and dryness. Rezpegaldesleukin’s ability to boost regulatory T cells may help calm this overactive immune response.
The medication is also under investigation for severe to very severe alopecia areata, an autoimmune condition characterized by patchy hair loss. In alopecia areata, the immune system attacks hair follicles. By enhancing Treg function, rezpegaldesleukin aims to prevent these attacks and promote hair regrowth. Early research has also explored its use in other autoimmune conditions like psoriasis, systemic lupus erythematosus (SLE), and ulcerative colitis, where Treg dysfunction is a factor.
Clinical Development and Patient Considerations
Rezpegaldesleukin is undergoing clinical trials to assess its efficacy and safety. It has received Fast Track designation from the U.S. Food and Drug Administration (FDA) for the treatment of moderate-to-severe atopic dermatitis in adults and pediatric patients 12 years and older. This designation is granted to investigational therapies that address serious conditions and have the potential to fulfill an unmet medical need, allowing for more frequent interactions with the FDA during development.
The medication is a self-administered injection. In Phase 1b and 2b studies for atopic dermatitis, rezpegaldesleukin showed a favorable safety profile. The most common side effects were mild to moderate local injection site reactions. These reactions were typically self-resolving, and a very small percentage of patients discontinued treatment due to them.
Less common side effects included eosinophilia, pyrexia (fever), headache, and arthralgia (joint pain). Studies have not shown an increased risk of conjunctivitis, oral herpes, or oral ulcers, sometimes associated with other atopic dermatitis therapies.
Proof-of-concept efficacy data from a Phase 1b study in atopic dermatitis patients showed rapid improvement in disease outcomes during a 12-week treatment period, with benefits sustained for at least 36 weeks after treatment cessation. The ongoing REZOLVE-AD Phase 2b study met its primary and key secondary endpoints, showing significant improvements in measures like Eczema Area and Severity Index (EASI) scores. Further data from the REZOLVE-AA study in alopecia areata are anticipated, and long-term maintenance data for atopic dermatitis are expected in early 2026.