Rezpegaldesleukin Shows Sustained Benefit in Moderate-to-Severe Atopic Dermatitis in Phase 2 b trial
The phase 2b REZOLVE-AD trial enrolled 393 adults with moderate-to-severe atopic dermatitis across approximately 110 global sites, randomizing them to three subcutaneous doses of rezpegaldesleukin or placebo. Patients who achieved EASI-50 at Week 16 were re-randomized to blinded maintenance therapy every 4 or 12 weeks, while nonresponders entered an extended treatment arm. Results from the 36-week maintenance phase of the 52-week study demonstrated sustained clinical benefits of this novel Treg-targeting biologic.
The global REZOLVE-AD Phase 2b study enrolled 393 patients with moderate-to-severe atopic dermatitis. Patients were randomized (3:3:3:2) to receive subcutaneous treatment with three doses of rezpegaldesleukin or placebo for a 16-week induction period. Following a 16-week induction period, rezpegaldesleukin-treated patients who achieved Eczema Area Severity Index (EASI) percent score reductions of at least 50 were re-randomized (1:1) to continue at the same induction dose given monthly (Q4W) or quarterly (Q12W) through week 52 in a blinded 36-week maintenance period. Patients that did not achieve an
Rezpegaldesleukin Demonstrated Long-Term Durability and Continued AD Disease Symptom Improvement in Maintenance
- Durability of Treatment Effect: Q4W and Q12W dosing regimens resulted in sustained disease control for
EASI -75,EASI -90, validated Investigator Global Assessment of Atopic Dermatitis (vIGA-AD) response, and Itch Numerical Rating Scale (NRS) response, with the 24 µg/kg Q4W and Q12W regimens showing the highest maintenance of response at week 52. - New and Deepening of Response Over Time: A meaningful proportion of patients achieved new
EASI -75,EASI -90, Itch NRS and vIGA-AD 0/1 responses at Week 52, supporting increased disease control with prolonged therapy and less frequent dosing. - Meaningful Conversions to
EASI -100: In maintenance, a 2 to 5-fold increase in percentage of patients who achievedEASI -100 was observed in the 24 µg/kg Q4W and Q12W dosing regimens. Among all re-randomized patients from week 16 to week 52, Q4W maintenance dosing increasedEASI -100 response from 4% to 22% and Q12W dosing increasedEASI -100 response from 9% to 18%. Among re-randomized patients who had anEASI -75 or vIGA-AD response at maintenance baseline, Q4W dosing increasedEASI -100 response from 6% to 30% and Q12W dosing increasedEASI -100 response from 14% to 27%.
"These data show that rezpegaldesleukin, as a broad-based Treg agonist, is emerging as one of the most important mechanisms in development to treat atopic dermatitis," said
"These data show that rezpegaldesleukin, as a broad-based Treg agonist, is emerging as one of the most important mechanisms in development to treat atopic dermatitis," said
Week 52 Efficacy Measurements in Maintenance
N=xx is the entire maintenance population; (n=xx) is the denominator which equals the number of responders at Week 16; % represents proportion of patients who maintained that response at Week 52
*Only patients with baseline Itch NRS ≥ 4 used as denominator for assessing Itch NRS response
N=xx is the entire maintenance population; (n=xx) is the denominator which equals the number of responders at Week 16; % represents proportion of patients who maintained that response at Week 52
*Only patients with baseline Itch NRS ≥ 4 used as denominator for assessing Itch NRS response
"These data highlight that rezpegaldesleukin offers a completely novel therapeutic modality for the potential treatment of atopic dermatitis with numerous advantages to existing classes," said David Rosmarin M.D., Chair, Department of Dermatology and Associate Professor of Dermatology, Indiana University School of Medicine. "Importantly, we don't see any increased risk of incidence of conjunctivitis, oral herpes, oral ulcers or malignancies with this MOA as has been observed with other mechanisms. The investigators are looking forward to initiating Phase 3 studies as quickly as possible."
"These new REZOLVE-AD study results reinforce the promise of the Treg mechanism to treat atopic dermatitis," said Howard W. Robin, President and CEO of Nektar Therapeutics. "In the induction part of REZOLVE-AD, we saw a rapid onset of EASI-75 response and itch relief early in treatment, and, for the first time with Tregs, we observed meaningful improvement in self-reported asthma control in patients with co-morbid asthma. The combined data from induction and maintenance now showcase the potential of a Treg biologic to offer compelling efficacy and safety advantages and less frequent maintenance dosing as compared to current mechanisms. We look forward to advancing to Phase 3 studies quickly with the goal of submitting a BLA in 2029."
The safety profile of rezpegaldesleukin in maintenance was consistent with observations from the induction part of the study. Rezpegaldesleukin was well-tolerated with no new safety concerns identified during the 36-week maintenance and escape periods. The discontinuation rate due to adverse events was 3.5% for all aggregated patients. Overall rates of treatment-emergent adverse events (TEAEs) were 72% for re-randomized rezpegaldesleukin treated patients, 65% for placebo patients in maintenance, and 83% for all escape patients. The most frequent TEAE was injection site reactions, nearly all of which were mild (77%), and which occurred at a lower rate and frequency than observed in the initial induction part of the study (discontinuation rate due to injection site reactions was 0.7%).
About Rezpegaldesleukin
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. Rezpegaldesleukin is a potential first-in-class resolution therapeutic that may address the underlying immune system imbalance in people with many autoimmune and inflammatory conditions. It targets the interleukin-2 receptor complex in the body in order to stimulate proliferation of powerful inhibitory immune cells known as regulatory T cells. By activating these cells, rezpegaldesleukin may act to bring the immune system back into balance.
In February 2025, the U.S. Food and Drug Administration (FDA) granted Fast Track designation for rezpegaldesleukin for the treatment of adult and pediatric patients 12 years of age and older with moderate-to-severe atopic dermatitis whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable. In July 2025, the FDA granted Fast Track designation for rezpegaldesleukin for the treatment of severe alopecia areata (AA) in adults and pediatric patients 12 years of age and older who weigh at least 40 kg.
Rezpegaldesleukin is being developed as a self-administered injection for a number of autoimmune and inflammatory diseases. It is wholly-owned by Nektar Therapeutics.
About Atopic Dermatitis
Atopic Dermatitis is the most common type of eczema, affecting approximately 30 million people in the United States[1]. AD is characterized by a defect in the skin barrier, which allows allergens and other irritants to enter the skin, leading to an immune reaction and inflammation.
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