APG777 Trial Demonstrates Efficacy, Safety in AD

Current treatments for atopic dermatitis (AD) often require frequent injections, placing a considerable burden on individuals managing this chronic condition.¹ APG777 is a first-in-class, humanized monoclonal IgG1 antibody specifically designed to overcome this limitation. By binding to and neutralizing IL-13, a key cytokine in the inflammatory cascade of AD, APG777 directly targets the underlying disease mechanism. Importantly, the antibody was engineered with an extended half-life to optimize pharmacokinetics and reduce dosing frequency, with the goal of meaningfully lowering treatment burden.

The primary efficacy and safety results from the 16-week induction phase (Part A) of the phase 2 APEX trial (NCT06395948) were recently reported at EADV 2025, evaluating APG777 in patients with moderate to severe AD.²

Materials and Methods

The APEX trial is a 2-part, multicenter, randomized, placebo-controlled phase 2 study. Part A includes a 16-week induction period followed by a 36-week maintenance phase. Eligible patients were biologic-naïve adults with moderate to severe AD, defined by an Eczema Area and Severity Index (EASI) ≥16, a validated Investigator’s Global Assessment for AD (vIGA-AD) score ≥3, and ≥10% body surface area (BSA) involvement.

Participants were randomized 2:1 to receive APG777 or placebo. The APG777 regimen consisted of a 720 mg loading dose at day 1 and week 2, followed by 360 mg doses at weeks 4 and 12.

The primary endpoint was mean percent change from baseline in EASI at week 16. Secondary endpoints included achievement of EASI-75, EASI-90, and vIGA-AD 0/1. Change from baseline in weekly mean Itch Numerical Rating Scale (I-NRS) was also assessed. Post-hoc exposure–response analyses were performed.

Results

Treatment with APG777 resulted in robust and statistically significant efficacy across endpoints:

• Skin clearance: At week 16, APG777 achieved a 71.0% mean reduction in EASI versus 33.8% with placebo (P<0.001). Improvements were evident as early as week 2 (-35.4% vs. -20.8%, P=0.01) and sustained through week 16.
• Response rates: Significantly more patients on APG777 achieved EASI-75 at week 16 compared with placebo (66.9% vs. 24.6%, P<0.001). Similar improvements were seen for EASI-90 and vIGA-AD 0/1.
• Itch relief: Rapid improvement in pruritus was observed as early as day 3, with sustained benefit through week 16.
• Exposure–response: Higher APG777 exposure correlated with greater reductions in EASI and higher EASI-75 response rates.

Safety: APG777 was generally well-tolerated. The most common treatment-emergent adverse events were noninfective conjunctivitis (14.6% vs. 2.4% with placebo) and upper respiratory tract infection (8.5% vs. 12.2%). Most cases of conjunctivitis were mild/moderate, transient, and resolved during induction.

Conclusion

The 16-week induction results from the APEX study demonstrate that APG777, a novel half-life–extended anti–IL-13 antibody, delivers significant improvements in both skin symptoms and itch in patients with moderate to severe AD. Its rapid onset of action, favorable safety profile, and reduced dosing frequency suggest meaningful advantages over current therapies.

These findings support continued development of APG777, including evaluation of extended dosing intervals (every 12 or 24 weeks) in the ongoing maintenance phase and exploration of higher dose levels in part B of the trial. The clear exposure–response relationship highlights the potential to further optimize dosing strategies and maximize patient benefit.

References

1. Gallagher K, Halperin-Goldstein S, Paller AS. New treatments in atopic dermatitis update. Ann Allergy Asthma Immunol. Published online June 23, 2025. doi:10.1016/j.anai.2025.06.020
2. Guttman-Yassky E. APG777, a novel, half-life extended anti-IL-13 antibody, demonstrates safety and efficacy in moderate-to-severe atopic dermatitis: 16-week results from the phase 2 APEX study. Presented at: European Academy of Dermatology and Venereology Congress 2025; September 17-20, 2025; Paris, France.