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Introduction <p>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.</p> Methods <p>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&#xa0;mg/kg) or placebo by subcutaneous injection for 12&#xa0;weeks. The primary endpoint was the proportion of participants achieving ≥ 75% improvement in EASI score (EASI-75) from baseline at week&#xa0;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&#xa0;12. Safety, immunogenicity, and pharmacodynamics were assessed through week&#xa0;36.</p> Results <p>Fifty-one participants were randomized (JNJ-67484703: <i>n</i> = 34; placebo: <i>n</i> = 17). At week&#xa0;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] −&#xa0;4.8, 31.2]; <i>P</i> = 0.4590). Percentage improvement in EASI score was numerically greater with JNJ-67484703 versus placebo (−&#xa0;41.0% vs −&#xa0;20.8%; LSM difference −&#xa0;20.1%, 90% CI −&#xa0;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<sup>high</sup> CD4<sup>+</sup> T cells than PD-1<sup>low</sup> CD4<sup>+</sup> T cells at week&#xa0;12 (85.6% vs 47.7%).</p> Conclusion <p>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.</p> Trial Registration <p>EudraCT 2022-001528-14.</p>

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Efficacy and Safety of the PD-1 Agonist JNJ-67484703 in Participants with Atopic Dermatitis: Phase 2a, Randomized, Double-Blind, Placebo-Controlled Trial Results

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  • 出版模式：

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  • 发表日期：

    2026年4月20日

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  • Michael Cecchini,
  • Bartlomiej Kwiek,
  • Fang Liu-Walsh,
  • Michael Scully,
  • Jessica Harakal,
  • Erika H. Noss,
  • Ashley Orillion,
  • He Li,
  • Bin Gao,
  • Ilia Tikhonov

摘要

Introduction

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.

Methods

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.

Results

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-1high CD4+ T cells than PD-1low CD4+ T cells at week 12 (85.6% vs 47.7%).

Conclusion

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.

Trial Registration

EudraCT 2022-001528-14.