A novel regulatory T-cell therapy demonstrated significant improvements in moderate-to-severe atopic dermatitis and asthma symptoms in a phase 2b clinical trial, researchers reported at the American College of Allergy, Asthma and Immunology (ACAAI) Annual Scientific Meeting.
Rezpegaldesleukin, an IL-2 receptor pathway agonist that selectively expands regulatory T cells and enhances their function, met its primary endpoints in the REZOLVE-AD trial after 16 weeks of treatment. Rezpegaldesleukin aims to target the underlying immune dysregulation in atopic dermatitis rather than simply suppressing inflammation.
“These findings support further development of rezpegaldesleukin as a novel biologic treatment for atopic dermatitis and asthma,” noted in his presentation James Treat, MD, pediatric dermatologist at Children's Hospital of Philadelphia and professor of clinical pediatrics at the University of Pennsylvania, who presented the findings during the conference.
Trial Design and Patient Population
REZOLVE-AD (NCT06136741) is an ongoing randomized, double-blind, placebo-controlled phase 2b study evaluating rezpegaldesleukin in adult patients with moderate-to-severe atopic dermatitis. The study enrolled 393 patients who were randomized 3:3:3:2 to receive subcutaneous injections of rezpegaldesleukin 24 μg/kg every two weeks (104 patients), 18 μg/kg every two weeks (106 patients), 24 μg/kg every four weeks (110 patients), or placebo (73 patients) for 16 weeks.
Researchers assessed atopic dermatitis severity using the Eczema Area and Severity Index (EASI), Validated Investigator Global Assessment (vIGA-AD) and Numerical Rating Scale for itch (NRS-Itch). Among the study population, 99 patients had asthma, including 25 with uncontrolled disease at baseline, defined as an Asthma Control Questionnaire-5 score of 1.5 or higher.
Primary Efficacy Results
The highest-dose regimen of rezpegaldesleukin 24 μg/kg every two weeks showed statistically significant improvements across multiple measures of atopic dermatitis severity compared with placebo at week 16.
Patients receiving 24 μg/kg of rezpegaldesleukin showed a significant reduction in the mean percent change in EASI scores (p<0.001). The proportion of patients achieving 75% improvement in EASI was significantly higher than placebo (p<0.001), as was the proportion achieving 90% improvement (p<0.05).
Treatment with rezpegaldesleukin 24 μg/kg every two weeks also resulted in significant improvements in vIGA-AD scores of 0 or 1, indicating clear or almost clear skin (p < 0.05), as well as in itch response, defined as at least a 4-point reduction on the numerical rating scale (p<0.01).
Treatment effects appeared consistent across patient subgroups stratified by baseline disease severity, sex, geographic region and presence of asthma comorbidity.
Asthma Outcomes
Among patients with self-reported asthma who completed ACQ-5 assessments at baseline and week 16, those receiving rezpegaldesleukin 24 μg/kg every two weeks showed significant improvement in asthma control scores from baseline (p<0.05).
Among patients with uncontrolled asthma at baseline, 75% of those treated with rezpegaldesleukin 24 μg/kg achieved a clinically meaningful improvement, defined as a reduction of at least 0.5 points in ACQ-5 scores at week 16. The percentages of patients with uncontrolled asthma at baseline who achieved ACQ-5 response at week 16 were 63% with rezpegaldesleukin 18 μg/kg every two weeks and 57% with rezpegaldesleukin 24 μg/kg every four weeks.
Placebo-Crossover Data
Treat presented findings from an interim analysis of patients who crossed over from placebo to rezpegaldesleukin 24 μg/kg every two weeks at week 16. After 24 weeks of treatment with rezpegaldesleukin, these patients showed continued improvement, with mean EASI score reductions reaching 72% and EASI-75 response rates of 60%, compared with 8% and 0%, respectively, at the end of their placebo period.
Safety Profile
The researchers reported no new safety signals during the 16-week induction period. Treatment-emergent adverse events occurred in 80.3% of patients receiving rezpegaldesleukin compared with 57.5% receiving placebo. However, when excluding injection site reactions, the rates were similar between groups: 60.3% for rezpegaldesleukin versus 57.5% for placebo.
Injection site reactions were the most common adverse event, affecting 69.7% of patients on rezpegaldesleukin versus 4.1% on placebo. Most injection site reactions were mild to moderate, with only 0.4% classified as severe. Fewer than 1% of patients discontinued treatment due to injection site reactions.
Serious adverse events were rare, occurring in 1.6% of rezpegaldesleukin-treated patients and none in the placebo group. No treatment-related deaths occurred during the 16-week induction period.
Phase 3 Planning
Treat noted that pivotal phase 3 planning for moderate-to-severe atopic dermatitis is underway, including plans to assess the treatment effect in patients with comorbid asthma. The presentation data support a 24-week induction period using the 24 μg/kg every two weeks dosing regimen for the phase 3 program.
Illustration by Jennifer Bogartz
