Jennifer Soung, MD

OX40 for Atopic Dermatitis: A Target at a Crossroads

 is a heterogeneous inflammatory skin disease driven by immune dysregulation across multiple T cell axes — Th2, Th17, Th22, and others — making it notoriously difficult to treat consistently across patient populations. Current approved biologics and small molecules largely intervene downstream, targeting individual cytokines or intracellular signaling cascades. Effective as these agents are, disease recurrence upon treatment discontinuation remains a significant limitation for many patients.

The OX40 pathway represented a potential workaround. By intervening upstream — at the interface between antigen-presenting cells and T cells — OX40-targeted therapies theoretically offered not just symptom control but the prospect of durable remission, including suppression of effector memory T cells long thought responsible for disease persistence after treatment withdrawal. Two agents advanced into late-phase development targeting this pathway: rocatinlimab, an anti-OX40 receptor monoclonal antibody developed by Kyowa Kirin with Amgen, and amlitelimab, an anti-OX40 ligand monoclonal antibody developed by Sanofi.

Rocatinlimab demonstrated clinically meaningful efficacy in the pivotal ROCKET-IGNITE and ROCKET-HORIZON Phase 3 trials, results of which were published in 

 in November 2025.¹ IGNITE enrolled 769 adults with moderate-to-severe atopic dermatitis, including patients previously treated with a biologic or systemic JAK inhibitor. At week 24, EASI-75 was achieved by 42% of patients receiving the 300 mg dose and 36% receiving 150 mg, compared with 13% on placebo (

 < .001 for both). vIGA-AD 0/1 was achieved by 24% and 19% of the respective dose groups versus 9% on placebo (

 = .002, respectively). In the HORIZON monotherapy trial, 33% of patients on rocatinlimab 300 mg achieved EASI-75 versus 14% on placebo (difference 19.1%; 95% CI, 12.4–25.2), with vIGA-AD 0/1 reached by 19% versus 7%.¹ 

However, rocatinlimab was associated with adverse events including pyrexia, chills, and aphthous ulcers, and its efficacy was not demonstrated to be superior to dupilumab in head-to-head data. In March 2026, Kyowa Kirin and Amgen announced the discontinuation of all rocatinlimab clinical trials following a planned safety review that identified 1 newly confirmed and 1 suspected case of Kaposi sarcoma across the global program, in addition to a previously confirmed case — findings the companies concluded suggested a potential mechanistic link to OX40 pathway modulation.²

The key mechanistic distinction separating rocatinlimab from amlitelimab is not simply target specificity but the downstream consequence of that distinction. Rocatinlimab binds the OX40 receptor on activated T cells and, critically, depletes those cells via antibody-dependent cellular cytotoxicity. Amlitelimab targets the OX40 ligand on dendritic cells and is explicitly non-depleting, blocking signaling through steric hindrance rather than cellular elimination. Sanofi has continued to advance its program despite disclosing 1 case of Kaposi's sarcoma in the ATLANTIS long-term safety study — occurring in a patient with known risk factors — and presented 3-trial Phase 3 data from COAST 1, COAST 2, and SHORE as late-breaking research at the 

2026 American Academy of Dermatology Annual Meeting

Across all 3 trials, amlitelimab was evaluated at dosing intervals of every 4 weeks (Q4W) and every 12 weeks (Q12W). In COAST 1 (n = 601), vIGA-AD 0/1 was achieved by 21.1% of patients in the Q4W arm and 22.5% in the Q12W arm, versus 9.2% on placebo (

 ≤ .01 for both). EASI-75 rates were 35.9% (Q4W) and 39.1% (Q12W) versus 19.1% on placebo (

 < .001 for both). In COAST 2, vIGA-AD 0/1 rates were 25.3% and 25.7% for Q4W and Q12W, respectively, compared with 14.8% on placebo (

 ≤ .025 for both); EASI-75 and peak pruritus numerical rating scale response reached nominal significance, though the more stringent vIGA-AD 0/1 with barely perceptible erythema endpoint did not. The combination therapy SHORE trial produced the highest response rates across the program, with vIGA-AD 0/1 achieved by 28.7% (Q4W) and 32.3% (Q12W) versus 16.8% on placebo, and EASI-75 rates approaching 47–48% in treated arms versus 32.3% for placebo.⁵ A key feature across all 3 datasets was progressive efficacy with no evidence of plateau at week 24, suggesting continued improvement beyond the primary endpoint window. In the ATLANTIS long-term safety analysis, vIGA-AD 0/1 rates increased from 35.4% at week 24 to 50.3% at week 52, with EASI-75 rising from 62.9% to 76.5% over the same period.³ COAST 2 did not meet its European co-primary estimand endpoints, a distinction with potential regulatory implications outside the United States.

Whether amlitelimab's mechanistic and safety profile is sufficiently differentiated from rocatinlimab's to overcome the shadow cast by the class-level Kaposi's sarcoma signal is an active point of debate among clinicians. 

 spoke with 3 leading dermatologists to explore both sides of this question, what the Phase 3 data show, and what comes next for OX40 targeting in atopic dermatitis.

 — Co-Chief Medical Officer and Director of Clinical Research, Frontier Dermatology

— Professor and Chief of Dermatology, University of California, Los Angeles

 — Director of Clinical Research, Southern California Dermatology and faculty at Harbor-UCLA Medical Center

Armstrong’s disclosures include AbbVie, Almirall, Arcutis, ASLAN, Beiersdorf, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, Dermira, EPI, Incyte, Janssen, LEO Pharma, Eli Lilly, Nimbus, Novartis, Ortho Dermatologics, Parexel, Pfizer, Regeneron, Sanofi, Sun, and UCB. Soung’s disclosures include AbbVie, Amgen, Arcutis, Aslan, Bristol Myers Squibb, Coval Biopharma, Dermavant, Eli Lilly, Johnson & Johnson, KoBio Labs, National Psoriasis Foundation, Novartis, Ortho Dermatologic, Oruka, Pfizer, Regeneron/Sanofi, and UCB. Song’s disclosures include AbbVie, Alphyn Biologics, Amgen, Apogee, Arcutis, Bristol Myers Squibb, Boehringer Ingelheim, Dermavant, DermBiont, Galderma, Incyte, Janssen, LEO Pharma, MoonLake, Novartis, Ortho, Pfizer, Regeneron, Sanofi, Sun Pharmaceutical Industries, Timber Pharmaceuticals, and UCB.

Guttman-Yassky E, et al. Efficacy and safety of rocatinlimab for the treatment of moderate-to-severe atopic dermatitis in ROCKET-IGNITE and ROCKET-HORIZON: two global, double-blind, placebo-controlled, randomised phase 3 clinical trials. 

 2025;406(10510):1424-1442. doi:10.1016/S0140-6736(25)01865-3

Kyowa Kirin Co., Ltd. Kyowa Kirin announces discontinuation of rocatinlimab clinical trials. GlobeNewswire. Published March 3, 2026. 

https://www.globenewswire.com/news-release/2026/03/03/3248303/0/en/Kyowa-Kirin-Announces-Discontinuation-of-Rocatinlimab-Clinical-Trials.html

Sanofi. Sanofi's amlitelimab met all primary and key secondary endpoints in the COAST 1 phase 3 study in adults and adolescents with atopic dermatitis. Press release. Published September 4, 2025. 

https://www.sanofi.com/en/media-room/press-releases/2025/2025-09-04-05-00-00-3144170

Sanofi. Sanofi's amlitelimab confirms its potential in atopic dermatitis. Press release. Published January 23, 2026. 

https://www.sanofi.com/en/media-room/press-releases/2026/2026-01-23-06-00-00-3224400

Sanofi. AAD: new results from Sanofi's amlitelimab phase 3 studies in atopic dermatitis presented in late-breaking research session. Press release. Published March 28, 2026. 

https://www.sanofi.com/en/media-room/press-releases/2026/2026-03-28-15-00-00-3264184

Videos

ICONIC-LEAD: 1 Year Icotrokinra Data Confirm Durable Psoriasis Clearance, PRO Improvements in Adults, Adolescents, With Jennifer Soung, MD

One-year data from the phase 3 ICONIC-LEAD trial confirm that icotrokinra (ICOTYDE) delivers durable skin clearance and meaningful patient-reported improvements across adults and adolescents with moderate-to-severe plaque psoriasis with no new safety signals through week 52.

Icotrokinra is the first and only targeted oral peptide blocking the IL-23 receptor after being approved by the United States Food and Drug Administration (FDA) on March 18, 2026 for moderate-to-severe plaque PsO in adults and adolescents 12 and older.

To discuss the findings presented at the 

2026 American Academy of Dermatology (AAD) Annual Meeting

 held in Denver, Colorado, from March 27-31, 

 spoke with Jennifer Soung, MD, Founder and Director of Clinical Research at Southern California Dermatology in Santa Ana, California, and ICONIC-LEAD investigator. ICONIC-LEAD enrolled 684 patients ≥12 years (adults, n = 618; adolescents, n = 66) with moderate-to-severe plaque PsO (BSA ≥10%, PASI ≥12, IGA ≥3). In the adult randomized-withdrawal analysis, of 341 week-24 responders re-randomized 1:1 to continue icotrokinra or withdraw to placebo, continuous icotrokinra produced superior maintenance of PASI 75 (89% vs. 30%; 

 <.001) at week 52, with median time to loss of response not reached in those continuing therapy versus 16.9 and 10.1 weeks for PASI 75 and PASI 90, respectively, among those re-randomized to placebo.

The adolescent data, presented across 2 companion posters at AAD, were particularly notable given the absence of approved advanced oral options for this population. Among adolescents randomized to icotrokinra (n = 44; mean age 15.0 years, mean PASI 19.8, 70% moderate/30% severe), 91% achieved IGA 0/1 and 86% achieved PASI 90 by week 52, with 89% of week-24 IGA 0/1 responders and 92% of week-24 PASI 90 responders maintaining those responses at week 52. Complete skin clearance rates were also substantial, with 64% achieving IGA 0 and 57% achieving PASI 100 during weeks 24–52. On patient-reported outcomes, more than 80% of icotrokinra-randomized adolescents reported clinically meaningful itch improvement (≥4-point PSSD improvement) through weeks 24–52, more than 50% reported complete symptom resolution (PSSD symptom score 0), approximately 40% reported complete sign resolution (PSSD sign score 0), and more than 80% reported psoriasis no longer impacted their health-related quality of life (CDLQI 0/1) — with improvements observed as early as week 2. Through week 52, no adolescent discontinued due to an adverse event, no serious infections occurred, and no malignancies were reported, with the overall safety profile consistent with the placebo-controlled period.

“This is the first time an advanced systemic has concurrently received approval for adults and adolescents at the same time, and that's a game changer, because our adolescent patients don’t really want an injection,” Soung said. “We also saw such amazing skin clearance rates in our adolescent patients. So I think that, again, making PsO treatment more accessible and easier for our patients means more of our patients will benefit from these treatments.”

Soung’s reported disclosures include AbbVie, Amgen, Arcutis, Aslan, Bristol Myers Squibb, Coval Biopharma, Dermavant, Eli Lilly, Johnson & Johnson, KoBio Labs, National Psoriasis Foundation, Novartis, Ortho Dermatologic, Oruka, Pfizer, Regeneron/Sanofi, and UCB.

Soung J, Lebwohl MG, Hebert A, et al. Durability of icotrokinra (targeted oral peptide) effects in adolescents with moderate-to-severe plaque psoriasis: one-year results from the ICONIC-LEAD study. Poster presented at: American Academy of Dermatology Annual Meeting; March 27–31, 2026; Denver, CO. Poster P73600.

Soung J, Lebwohl MG, Hebert A, et al. Early and durable improvements in patient-reported outcomes with the targeted oral peptide icotrokinra in adolescents with moderate-to-severe plaque psoriasis: one-year results from the ICONIC-LEAD study. Poster presented at: American Academy of Dermatology Annual Meeting; March 27–31, 2026; Denver, CO. Poster P73603.

Johnson & Johnson. FDA approval of ICOTYDE™ (icotrokinra) ushers in new era for first-line systemic treatment of plaque psoriasis with a targeted oral peptide. Press release. March 18, 2026. 

https://www.jnj.com/media-center/press-releases/fda-approval-of-icotyde-icotrokinra-ushers-in-new-era-for-first-line-systemic-treatment-of-plaque-psoriasis-with-a-targeted-oral-peptide

Soung discussed how new 52-week data support icotrokinra's recent FDA approval, marketed as Icotyde.

Final reflections from physicians Stein Gold, Soung, and Cotter, emphasizing multidisciplinary, patient-focused advances in psoriasis and PsA care.

Closing Thoughts on the Impact of IL-23s in Psoriasis and Psoriatic Arthritis

, despite the expanding therapeutic landscape. Linda Stein Gold, MD, and her colleagues analyze patient- and provider-reported data from the 

 surveys, revealing that many patients remain dissatisfied with current therapies and that oral agents are overwhelmingly preferred over injectables. The experts discuss how patient lifestyle, comorbidities, and psychosocial burden influence shared decision-making and treatment adherence. They also interpret the 

International Psoriasis Council’s (IPC)

 and explore its implications for reducing “topical churn” and advancing systemic therapy earlier in the disease course.

 and its potential to close current gaps in care. The panel provides an in-depth review of the 

 clinical development program, summarizing the 

 trials, which demonstrated superior efficacy versus deucravacitinib at both 16 and 24 weeks, with favorable safety and tolerability. They also discuss new 

 showing sustained clearance and no new safety signals in adults and adolescents. The faculty reflect on ICO’s implications for adolescent psoriasis and how early, aggressive oral intervention may help prevent progression to psoriatic arthritis, marking a significant milestone in the evolution of oral IL-23–targeted therapy.

The final portion of the series shifts focus to 

managing active psoriatic arthritis (PsA)

. The experts discuss new findings from the 

 demonstrated the first clear evidence of IL-23–mediated inhibition of structural joint damage, reinforcing the rationale for early biologic use in high-risk patients. They compare APEX to prior IL-23 studies, discuss implications for therapy sequencing, and highlight other emerging data from 

 studies. In closing, Stein Gold and colleagues emphasize a forward-looking approach that integrates personalized therapy selection, early detection of PsA, and cross-specialty collaboration to elevate standards of psoriasis care

Highlights from Fall Clinical 2025, including emerging IL-23 and real-world data shaping the next phase of psoriasis research.

Jennifer Soung, MD

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