Nektar Therapeutics (NKTR) Study result summary

Study Overview and Objectives

• Phase 2b Resolve AD/REZOLVE-AD evaluated rezpegaldesleukin in moderate-to-severe atopic dermatitis, focusing on induction and maintenance dosing regimens, including monthly (Q4W) and quarterly (Q12W) schedules.

• Over 1,000 patients were treated, with 393 enrolled in the REZOLVE-AD study and 381 patient-years of exposure.

• Patients achieving at least EASI-50 after induction were re-randomized to Q4W or Q12W dosing for a blinded maintenance phase.

• Key endpoints included EASI-75, EASI-90, vIGA/vIGA-AD 0/1, Itch NRS, and EASI-100 at week 52.

• Eligibility required EASI ≥16, BSA ≥10%, and vIGA-AD ≥3 at screening and randomization.

Efficacy Results and Response Durability

• Both Q4W and Q12W regimens sustained high response rates at week 52: EASI-75 (71–92%), EASI-90 (57–81%), vIGA-AD 0/1 (59–86%), and Itch NRS (56–85%).

• Up to a 5-fold increase in EASI-100 (complete clearance) was observed, with Q4W increasing from 4% to 22% and Q12W from 9% to 18%.

• New and deepening responses were seen: up to 62% new EASI-75 responders in some arms, and 41–51% (Q4W) and 39–40% (Q12W) of non-responders at maintenance baseline became responders by week 52.

• Efficacy was consistent across moderate and severe subgroups and in patients with comorbid asthma.

• Rezpegaldesleukin compared favorably to dupilumab and amlitelimab, with higher or comparable maintenance of response and lower rates of worsening itch and vIGA.

Safety and Tolerability

• Rezpegaldesleukin was well-tolerated with a favorable safety profile and no new safety concerns over 52 weeks.

• Discontinuation due to adverse events was low (3.5%); most common adverse events were mild-to-moderate injection site reactions, decreasing with longer dosing intervals.

• No increased risk of infection, conjunctivitis, oral herpes, oral ulcers, cardiovascular events, or malignancy compared to placebo.

• Discontinuation due to injection site reactions was rare (0.7%).