Phase 2a Trial Of JNJ-67484703 In Atopic Dermatitis

Key Takeaways

• Week 12 EASI-75 was higher with JNJ-67484703 than placebo, but the between-group difference was not statistically significant.
• EASI improvement, EASI-50, and SCORAD also moved in a numerically favorable direction with JNJ-67484703.
• Adverse-event rates were similar between groups, two anti-drug antibody cases had no pharmacokinetic effect, and depletion of PD-1–expressing T cells was reported.

In a phase 2a trial of JNJ-67484703 in atopic dermatitis, week 12 EASI-75 reached 25.0% with JNJ-67484703 in adults with moderate-to-severe atopic dermatitis. Investigators conducted a randomized, double-blind, placebo-controlled study of this PD-1–agonizing/depleting humanized IgG1 antibody in adults with active disease. Efficacy outcomes numerically favored active treatment, but the between-group difference for the primary endpoint did not reach statistical significance versus placebo.

Eligible participants were adults with moderate-to-severe atopic dermatitis, an EASI score of at least 16, and inadequate response to standard treatments. Participants were randomized 2:1, with 34 assigned to JNJ-67484703 and 17 to placebo. Treatment consisted of 3 mg/kg by subcutaneous injection for 12 weeks, and EASI-75 at week 12 was the primary endpoint. Safety, immunogenicity, and pharmacodynamics were also assessed through week 36. These design details frame the week 12 efficacy results and the follow-up safety and pharmacodynamic findings.

At week 12, EASI-75 was 25.0% with JNJ-67484703 and 11.8% with placebo, with a least-squares mean difference of 13.2%, a 90% CI of −4.8 to 31.2, and P=0.4590. Percentage change in EASI was −41.0% with JNJ-67484703 and −20.8% with placebo, with a least-squares mean difference of −20.1% and a 90% CI of −41.5 to 1.3. EASI-50 and SCORAD also numerically improved with JNJ-67484703. Across these efficacy measures, outcomes numerically favored JNJ-67484703, but statistical separation from placebo was not established in the reported results.

Adverse events occurred in 88.2% of participants receiving JNJ-67484703 and 82.4% receiving placebo. Two participants developed antibodies against JNJ-67484703, and these cases were not associated with a pharmacokinetic effect. Investigators also reported rapid, sustained, and reversible depletion of PD-1–expressing T cells, with a greater median reduction at week 12 in PD-1high CD4+ T cells than PD-1low CD4+ T cells, at 85.6% versus 47.7%. The authors characterized JNJ-67484703 as well tolerated but not statistically superior to placebo in this trial.