Interim Analysis Leads to Early Termination of DUPLEX-AD Study

Atopic dermatitis (AD) remains a heterogeneous, chronic inflammatory skin disease with a substantial burden in patients with moderate to severe disease. Despite the availability of targeted biologics and small molecules, a proportion of patients experience inadequate disease control, loss of response, or intolerance, underscoring the continued need for new therapeutic options.¹ Against this backdrop, the phase 2b DUPLEX-AD study evaluated the efficacy and safety of JNJ-95475939 (JNJ-5939), an investigational subcutaneously administered agent, in adults with moderate to severe AD.²

DUPLEX-AD (NCT06881251) was a multicenter, randomized, double-blind, placebo- and active-controlled, parallel-group, dose-ranging study. Participants were randomized to 1 of 5 arms: an active comparator arm receiving dupilumab, 3 experimental arms receiving different dose regimens of JNJ-95475939, and a placebo arm that crossed over to JNJ-95475939 after week 10. Triple masking was employed, including participants, investigators, and care providers.³

The primary endpoint was the proportion of participants achieving EASI-75 at week 12. Secondary endpoints included higher thresholds of skin clearance (EASI-90 and EASI-100), validated Investigator Global Assessment for AD (vIGA-AD) responses, percent change from baseline in EASI score, and multiple patient-reported outcomes assessing pruritus, skin pain, and sleep disturbance. Efficacy was assessed at multiple time points through week 24 to evaluate both early response and durability. Safety outcomes included treatment-emergent adverse events and serious adverse events.

A planned interim analysis determined that the study met pre-specified criteria for early termination. According to Johnson & Johnson, JNJ-95475939 did not achieve the level of efficacy required to justify further development in AD. While detailed efficacy data have not been publicly disclosed, the decision suggests that improvements in key endpoints such as EASI-75 at week 12 did not sufficiently differentiate the investigational agent from placebo or compare favorably with the active control.

From a safety perspective, JNJ-95475939 was reported to be generally well tolerated. No new safety signals emerged during the interim review, and adverse event monitoring did not identify safety concerns that contributed to the study’s discontinuation. This distinction is clinically relevant, as the decision to halt development was driven by efficacy considerations rather than tolerability or risk profile.

The inclusion of dupilumab as an active comparator is notable, as it reflects current expectations in AD drug development. With established biologics demonstrating robust EASI and vIGA responses, investigational agents are increasingly evaluated against a higher efficacy benchmark. The DUPLEX-AD results highlight the challenge of demonstrating incremental or competitive benefit in an increasingly crowded treatment landscape, particularly in biologic-naïve and biologic-experienced patient populations.

Although JNJ-95475939 will not advance further in AD based on these findings, the trial contributes useful information for clinicians and researchers. The comprehensive assessment of clinician-reported and patient-reported outcomes aligns with evolving standards in AD trials, where symptom burden, sleep impact, and quality-of-life measures are increasingly emphasized alongside skin clearance.

Johnson & Johnson has reiterated its continued commitment to AD research and development, citing an ongoing pipeline of clinical and preclinical programs targeting the disease. From a clinical standpoint, the early termination of DUPLEX-AD underscores the importance of rigorous interim analyses and predefined criteria in guiding development decisions.

References

1. Bai R, Zheng Y, Dai X. Atopic dermatitis: diagnosis, molecular pathogenesis, and therapeutics. Mol Biomed. 2025;6(1):71. Published 2025 Oct 6. doi:10.1186/s43556-025-00313-3
2. Johnson & Johnson statement on the phase 2b DUPLEX-AD study. New release. Johnson & Johnson. Published December 26, 2025. Accessed January 7, 2026. https://www.jnj.com/media-center/press-releases/johnson-johnson-statement-on-the-phase-2b-duplex-ad-study
3. A study of JNJ-95475939 in the treatment of participants with moderate to severe atopic dermatitis (AD) (DUPLEX-AD). ClinicalTrials.gov. Updated October 10, 2025. Accessed January 7, 2027. https://clinicaltrials.gov/study/NCT06881251#study-overview