お知らせ • Feb 10
Nektar Therapeutics Announces New REZOLVE-AD Maintenance Data in Atopic Dermatitis Demonstrate Rezpegaldesleukin Resulted in Durable and New Responses Across Key Disease Measurements with Both Monthly and Quarterly Dosing
Nektar Therapeutics announced positive results from the 36-week blinded maintenance period of the 52-week REZOLVE-AD study of rezpegaldesleukin, a novel regulatory T-cell (Treg) biologic, in patients with moderate-to-severe atopic dermatitis (AD). 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 EASI-50 during the 16-week induction period entered into a treatment escape arm for up to 36 weeks. 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 achieved EASI-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 increased EASI-100 response from 4% to 22% and Q12W dosing increased EASI-100 response from 9% to 18%. Among re-randomized patients who had an EASI-75 or vIGA-AD response at maintenance baseline, Q4W dosing increased EASI-100 response from 6% to 30% and Q12W dosing increased EASI-100 response from 14% to 27%. Week 52 efficacy measurements in maintenance: Maintenance of response among re-randomized patients achieving EASI-50 in 16-week induction: 24 µg/kg Q4W (pooled) N=55, EASI-75 71%(n=36), EASI-90 80%(n=18), vIGA-AD 0/1 85%(n=14), Itch NRS 75%(n=25); 24 µg/kg Q12W (pooled) N=56, EASI-75 83%(n=35), EASI-90 78%(n=20), vIGA-AD 0/1 63%(n=21), Itch NRS 77%(n=17); 18 µg/kg Q4W N=28, EASI-75 81%(n=20), EASI-90 57%(n=8), vIGA-AD 0/1 81%(n=12), Itch NRS 56%(n=14); 18 µg/kg Q12W N=28, EASI-75 76%(n=19), EASI-90 57%(n=7), vIGA-AD 0/1 62%(n=9), Itch NRS 61%(n=6). 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. New responses among re-randomized patients achieving EASI-50 in 16-week induction: 24 µg/kg Q4W (pooled) N=55, EASI-75 51%(n=19), EASI-90 33%(n=37), vIGA-AD 0/1 41%(n=41), Itch NRS 33%(n=26); 24 µg/kg Q12W (pooled) N=56, EASI-75 39%(n=21), EASI-90 26%(n=36), vIGA-AD 0/1 40%(n=35), Itch NRS 18%(n=32); 18 µg/kg Q4W N=28, EASI-75 17%(n=8), EASI-90 37%(n=20), vIGA-AD 0/1 23%(n=16), Itch NRS 31%(n=13); 18 µg/kg Q12W N=28, EASI-75 62%(n=9), EASI-90 33%(n=21), vIGA-AD 0/1 36%(n=19), Itch NRS 18%(n=17). 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. 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%). The global 393-patient Phase 2b study was conducted in patients with moderate to severe atopic dermatitis. Patients were randomized (3:3:3:2) to receive subcutaneous treatment with three doses of rezpegaldesleukin: a high dose of 24 µg/kg every two weeks (Q2W), a middle dose of 18 µg/kg every two weeks (Q2W), and a low dose of 24 µg/kg every four weeks (Q4W), or placebo Q2W. The primary endpoint and secondary endpoints were assessed at Week 16. Following the induction period, rezpegaldesleukin-treated patients who achieved EASI percent reductions of at least 50 were re-randomized (1:1) to continue at the same dose level on a Q4W or Q12W regimen through Week 52 in a blinded maintenance period. Placebo patients with EASI percent score reductions of at least 50 continue to receive placebo Q4W. The REZOLVE-AD trial was initiated in October 2023 and enrolled patients across approximately 110 sites globally. Enrollment included 68% of patients treated in Europe, 16% in the United States, 11% in Canada, and 5% in Australia. Key eligibility criteria included a minimum EASI score of 16.0, Body Surface Area (BSA) involvement of at least 10%, and a vIGA-AD score of at least 3 at screening and randomization. Rezpegaldesleukin is being developed as a self-administered injection for a number of autoimmune and inflammatory diseases. It is wholly-owned by Nektar Therapeutics.
