P183 APG777, a novel, half-life-extended anti-interleukin-13 antibody, demonstrates safety and efficacy in moderate-to-severe atopic dermatitis: 16-week results from the phase II APEX study

Abstract

APG777 is a first-in-class, half-life-extended, monoclonal antibody that blocks interleukin-13-mediated signalling. APG777 is being evaluated in moderate-to-severe AD with the goal of reducing injection burden. Primary efficacy and safety results are reported from the first 16 weeks of part A of the phase II APEX study (NCT06395948). APEX is a two-part, multicentre, randomized, placebo-controlled phase II trial. Part A consists of screening, 16-week induction and 36-week maintenance periods. Biologic-naive participants with moderate-to-severe AD were randomized 2 : 1 to APG777 or matched placebo. The primary endpoint was percentage change from baseline in Eczema Area and Severity Index (EASI) at week 16. Secondary endpoints included EASI 75 (≥ 75% improvement from baseline), EASI 90, Validated Investigator Global Assessment scale for Atopic Dermatitis (vIGA-AD) score of 0 or 1, and change in Individualized Numeric Rating Scale (I-NRS). Post hoc analyses were carried out to assess the relationship between APG777 exposure and efficacy. Treatment with APG777 resulted in a significant 71.0% reduction in EASI from baseline to Week 16 (vs. 33.8% placebo; P < 0.001). APG777 was well tolerated during the 16-week induction period, with greater reductions from baseline in EASI over placebo as early as week 2. Significantly greater percentages of participants in the APG777 group achieved EASI 75, EASI 90 and vIGA-AD 0/1 responses at week 16 compared with placebo, and significant improvement in I-NRS was observed as early as day 3. In post hoc analysis, higher exposures to APG777 led to greater reductions in EASI and higher EASI 75 responses. The most common adverse events (occurring in ≥ 5% of participants treated with APG777) included noninfective conjunctivitis and upper-respiratory-tract infection, occurring in 15% and 9% of participants in the APG777 group vs. 2% and 12% of participants in the placebo group, respectively. Most cases of noninfective conjunctivitis were mild or moderate and transient, and resolved by week 16. Treatment with APG777 led to significant improvement in the signs and symptoms of AD and was well tolerated. The primary results of this phase II trial support further evaluation of dosing every 12 weeks or every 24 weeks.