Efficacy and Safety of the PD-1 Agonist JNJ-67484703 in Participants with Atopic Dermatitis: Phase 2a, Randomized,...

Atopic dermatitis (AD) is a chronic, inflammatory skin disease with a high burden and unmet needs. Herein, we have assessed the efficacy and safety of JNJ-67484703, a programmed cell death protein 1 (PD-1)-agonizing/depleting humanized immunoglobulin G1 antibody, as a novel therapeutic approach in patients with AD.

In this phase 2a, double-blind, placebo-controlled study, adults with moderate-to-severe AD (Eczema Area and Severity Index [EASI] score ≥ 16) and an inadequate response to standard treatments were randomized (2:1) to receive JNJ-67484703 (3 mg/kg) or placebo by subcutaneous injection for 12 weeks. The primary endpoint was the proportion of participants achieving ≥ 75% improvement in EASI score (EASI-75) from baseline at week 12. Key secondary and exploratory endpoints included percentage change from baseline in EASI score, ≥ 50% improvement in EASI score (EASI-50), and change in SCORing Atopic Dermatitis (SCORAD) score at week 12. Safety, immunogenicity, and pharmacodynamics were assessed through week 36.

Fifty-one participants were randomized (JNJ-67484703: n = 34; placebo: n = 17). At week 12, a numerically higher proportion of participants in the JNJ-67484703 group achieved EASI-75 response versus placebo (25.0% vs 11.8%; least-squares mean [LSM] difference 13.2% 90% confidence interval [CI] - 4.8, 31.2]; P = 0.4590). Percentage improvement in EASI score was numerically greater with JNJ-67484703 versus placebo (- 41.0% vs - 20.8%; LSM difference - 20.1%, 90% CI - 41.5, 1.3). Similar numerically greater improvements with JNJ-67484703 were observed for EASI-50 and SCORAD scores. Adverse event rates were comparable between the JNJ-67484703 (88.2%) and placebo (82.4%) groups. Two participants developed antibodies against JNJ-67484703 without pharmacokinetic impact. JNJ-67484703 induced rapid, sustained, reversible depletion of PD-1-expressing T cells, with greater median percentage reduction of PD-1^high CD4⁺ T cells than PD-1^low CD4⁺ T cells at week 12 (85.6% vs 47.7%).

In this phase 2a trial in adults with moderate-to-severe AD, JNJ-67484703 was well-tolerated but did not demonstrate statistically significant benefit versus placebo.

EudraCT 2022-001528-14.