D3.164 - Early and Sustained Effect of Zumilokibart (APG777) in Atopic Dermatitis and Asthma: 16-Week Results from the Phase 2 APEX Study in Moderate-to-Severe AD and a Phase 1b Study in Mild-to-Moderate Asthma

IL-13 drives type 2 inflammation in both atopic dermatitis (AD) and asthma. Asthma commonly occurs in those with AD, yet limited therapies address both diseases. Zumilokibart (APG777) is a novel, half-life-extended anti-IL-13 antibody designed to achieve early and sustained therapeutic drug levels that support extended dosing intervals. Here, 16-week data from separate clinical trials in AD and asthma highlighting zumilokibart’s speed and durability of effect are presented.

In the phase 2 APEX Part A study (NCT06395948), adults (N=123) with moderate-to-severe AD were randomized 2:1 to zumilokibart (720mg: Day 1, Week 2; 360mg: Weeks 4, 12) or placebo. AD signs and symptoms were assessed using the Eczema Area and Severity Index (EASI) and Itch-Numeric Rating Scale (I-NRS). In an ongoing phase 1b asthma study (NCT06920901), 19 adults with mild-to-moderate asthma and baseline fractional exhaled nitric oxide (FeNO) ≥25 ppb were randomized 3:1 to receive a single dose of 720mg zumilokibart or placebo. Changes from baseline in FeNO were assessed. Safety and tolerability were evaluated in both studies. 

In APEX Part A, zumilokibart led to significant improvement in signs of AD by Week 2 [-35.4% change from baseline (CFBL) in EASI vs. -20.8% placebo; p=0.01]. At Week 16, 66.9% of zumilokibart-treated patients achieved EASI-75 compared to 24.6% of placebo-treated patients (p<0.001). Itch relief was obtained by 48 hours (-18.1% CFBL in I-NRS vs. -4.2% placebo; p<0.01). Progressive improvement in itch continued through Week 16 (-50.7% vs. -23.2%; p=0.001). Zumilokibart was well-tolerated; AEs in ≥5% zumilokibart-treated participants in APEX Part A included noninfective conjunctivitis and upper respiratory tract infection. In the phase 1b asthma study, a single dose of zumilokibart led to rapid suppression of FeNO, with maximal mean (±SE) change of -60.2% (±4.3) from baseline (vs. -10.2% (±8.7) with placebo) observed at Week 2 after dosing. Mean FeNO reductions >40 ppb from baseline were maintained at all timepoints from Week 2 through Week 16. Adverse events (AEs) were generally mild, and no grade 3 or serious AEs were observed.

Zumilokibart led to early and sustained improvements in markers of disease activity in separate studies in patients with AD and asthma. These results support continued investigation of zumilokibart as a novel therapy for AD and asthma with the potential to reduce injection burden for patients.