rocatinlimab (AMG 451) / Kyowa Kirin, Amgen - LARVOL DELTA

A Study With Self-administered Rocatinlimab in Adolescent and Adult Participants With Moderate-to-severe Atopic Dermatitis (clinicaltrials.gov) - P3 | N=151 | Completed | Sponsor: Amgen | Active, not recruiting ➔ Completed

Trial completion • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

Model-Informed Development of STAR-0310: Supporting Every-3-Month and Every-6-Month Dosing in Atopic Dermatitis (AAD 2026) - P1 | "A mechanistic model linking OX40 inhibition to Eczema Area and Severity Index (EASI) response was developed using data from telazorlimab and rocatinlimab, a structurally unrelated anti-OX40 antibody. Quantitative pharmacology modeling, supported by Phase 1a clinical data, positions STAR-0310 as a differentiated OX40 antagonist. Extended intervals, combined with high potency, and reduced ADCC, may reduce treatment burden and improve adherence, thus expanding therapeutic options in AD."

Atopic Dermatitis • Dermatitis • Dermatology • Immunology

Preclinical and first-in-human clinical evaluation of STAR-0310: A Differentiated OX40 Antagonist (AAD 2026) - P1 | "Results STAR-0310 demonstrated strong binding to human OX40 with robust inhibition of Th1, Th2, and Th17/22 cytokines, and 46-fold less Treg depletion than an in-house rocatinlimab analogue, consistent with its low-ADCC profile. Conclusion STAR-0310 combines high potency, reduced ADCC, extended half-life, and has potential for up to every six months administration. Interim clinical data align with preclinical results, and provide early proof of concept for STAR-0310 as a differentiated OX40 antagonist with potential to expand therapeutic options for moderate-to-severe AD and other immunologic diseases."

First-in-human • IO biomarker • P1 data • Preclinical • Atopic Dermatitis • Dermatitis • Immunology • Inflammation • IL2 • IL4 • TNFSF4

Dupilumab Outperforms Approved and Investigational Biologic Monotherapies in Moderate-to-Severe Atopic Dermatitis (AAD 2026) - " Seventeen RCTs (n=5508) compared dupilumab, tralokinumab, lebrikizumab, rocatinlimab, amlitelimab and rezpegaldesleukin with placebo at week 16 (rocatinlimab 300mg, 24 weeks). Dupilumab 300mg was the most effective biologic for moderate-to-severe AD, achieving both the strongest relative efficacy and the highest SUCRA ranking. Lebrikizumab emerged as a close second, particularly for itch improvement."

Atopic Dermatitis • Dermatitis • Dermatology • Immunology

The OX40/OX40L Axis Promotes Th2 Activity and Impairs Regulatory T Cell Function in Atopic Dermatitis. (PubMed, Allergy) - "AD patients exhibit significant upregulation of OX40 expression in effector and regulatory CD4+ T cells. Both subsets interact with OX40L-expressing cells in the skin, leading to the promotion of skin inflammation by downregulation of function and anti-inflammatory capacity of Tregs."

IO biomarker • Journal • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Inflammation • CD4 • IL10 • TNFRSF4 • TNFSF4

Rocatinlimab Does Not Impact Vaccination-Induced Immune Responses in Adults With Moderate-to-Severe Atopic Dermatitis: Results From the Phase 3 ROCKET-VOYAGER Trial (AAAAI 2026) - P3 | "Conclusions ROCA did not impact IgG responses to tetanus and meningococcal vaccination and no new safety signals were observed. Alongside ROCKET-HORIZON, IGNITE and SHUTTLE, VOYAGER supports ROCA use in patients with moderate-to-severe AD."

Clinical • Late-breaking abstract • P3 data • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Infectious Disease • Meningococcal Infections • Tetanus

Kyowa Kirin Announces Discontinuation of Rocatinlimab Clinical Trials (The Manila Times) - "This decision was informed by a recent planned safety update from the global rocatinlimab clinical program. Based on this update, Kyowa Kirin and Amgen have concluded that the potential risks may outweigh the benefits for the studied patient populations. This determination reflects the totality of emerging safety information, including previously reported safety risks...The most recent safety review conducted over the last several weeks identified emerging concerns of malignancies with possible viral or immune-related links....Both companies are currently notifying clinical trial investigators and regulatory authorities. After trial participants complete required safety follow-up visits, all studies will be formally terminated."

Trial termination • Asthma • Atopic Dermatitis • Immunology • Prurigo Nodularis

Kyowa Kirin to Regain Control of Rocatinlimab Development and Commercialization Program, Demonstrating Strong Commitment to Address High Unmet Medical Need in Atopic Dermatitis (The Manila Times) - "Regulatory submission is planned in the first half of 2026...Previously announced topline results from the primary analysis of the long-term safety extension study ROCKET-ASCEND demonstrated the potential for long-term therapeutic effect and extended dosing...Results from this trial will be presented at an upcoming medical conference....The company plans to file for regulatory approval in the U.S. first, followed by Japan, before expanding to other markets across the world as appropriate."

Commercial • FDA filing • Japan filing • P3 data • Atopic Dermatitis

Molecular differentiation of OX40 and OX40L targeted biologics using AlphaFold3 and molecular dynamics simulations. (PubMed, J Invest Dermatol) - "Our analysis suggests rocatinlimab and amlitelimab directly inhibit OX40-OX40L interactions by physically blocking the cognate OX40-OX40L interface via steric occlusion, whereas telazorlimab disrupts a critical OX40-OX40L bond. Together, this work provides molecular characterization of the epitopes of OX40 and OX40L targeted biologics emerging in dermatology."

Journal • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Inflammation • TNFSF4

Psychometric Evaluation of Worst Pruritus Numeric Rating Scale in Adults With Moderate-to-Severe Atopic Dermatitis. (PubMed, Dermatol Ther (Heidelb)) - P2 | "Worst Pruritus NRS is a reliable and valid patient-reported outcome measure to assess itch severity in clinical trial settings among adults with moderate-to-severe AD."

Journal • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Inflammation • Pruritus

The Role of OX40 Pathway Inhibition as a New Therapeutic Strategy for Atopic Dermatitis. (PubMed, BioDrugs) - "Amlitelimab, an anti-OX40L monoclonal antibody, has demonstrated sustained efficacy and a favorable safety profile in phase IIa and IIb trials. Rocatinlimab, targeting OX40, has also shown promising results in a phase IIb study and has progressed into multiple phase III trials, with supportive top-line data. In contrast, telazorlimab has shown more modest efficacy and has not advanced to later-stage development. Next-generation agents, including IMG-007, STAR-0310, APG990, and APG279, have been engineered with extended half-lives and attenuated antibody-dependent cellular cytotoxicity to support longer dosing intervals and improve tolerability. While these findings are encouraging, direct comparative studies among agents and versus established therapies are lacking, and long-term efficacy and safety data are still needed. This narrative review explores the role of the OX40/OX40L axis in atopic dermatitis pathogenesis and critically evaluates emerging therapies targeting..."

Journal • Review • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Inflammation • TNFSF4

Psychometric Evaluation of Skin Pain and Sleep Disturbance Numeric Rating Scales in Moderate-to-Severe Atopic Dermatitis. (PubMed, Dermatol Ther (Heidelb)) - "The AD SP-NRS and SD-NRS are reliable, valid, and responsive measures for assessing moderate-to-severe AD in adults and adolescents in clinical trials. The meaningful change thresholds identified in this study can be used in future clinical trials to interpret treatment effects."

Clinical • Journal • Atopic Dermatitis • CNS Disorders • Dermatitis • Dermatology • Immunology • Pain • Pruritus • Sleep Disorder

ROCKET-ASTRO: A Study to Evaluate Rocatinlimab (AMG 451) in Adolescent Participants With Moderate-to-severe Atopic Dermatitis (AD) (clinicaltrials.gov) - P3 | N=532 | Completed | Sponsor: Amgen | Active, not recruiting ➔ Completed

Trial completion • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

OX40 Ligand Inhibitors for Moderate-to-Severe Atopic Dermatitis: A Review of Phase II Clinical Trial Data. (PubMed, Skin Therapy Lett) - "On this basis, three phase II clinical trials have been conducted to evaluate the efficacy and safety of three different OX40-OX40L inhibitors (amlitelimab, rocatinlimab, and telazorlimab) in moderate-to-severe AD. Herein, we review the published data from these studies."

Journal • P2 data • Review • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Inflammation • TNFSF4

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. (PubMed, Lancet) - P3 | "Rocatinlimab treatment resulted in statistically significant and clinically meaningful improvements across clinical endpoints, including the coprimary endpoints of EASI-75 response and vIGA-AD score of 0 or 1, in comparison with placebo and had a clinically acceptable safety profile in adult patients with moderate-to-severe atopic dermatitis."

Journal • P3 data • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

Targeting OX40: rocatinlimab-a novel therapy for atopic dermatitis. (PubMed, Lancet) - No abstract available

Journal • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

Rocatinlimab With Concomitant Topical Therapy Significantly Improved Clinical Signs and Symptoms of Atopic Dermatitis in Adults: Results From the Phase 3 ROCKET-SHUTTLE Trial (ISDS 2025) - P3 | "ROCA combination therapy in a treatment-experienced patient population demonstrated statistically significant and clinically meaningful improvements vs PBO in AD clinical signs and symptoms and was generally well tolerated."

Clinical • P3 data • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Infectious Disease

Mount Sinai Dermatologist Reports Phase 3 Success for Rocatinlimab in Moderate-to-Severe Eczema (Mount Sinai Cancer) - "The landmark findings from the ROCKET-IGNITE and ROCKET-HORIZON studies were published today in The Lancet....Across the two global, double-blind, placebo-controlled randomized phase 3 clinical trials, nearly 1,500 patients were followed for 24 weeks, and rocatinlimab showed robust and lasting benefits. Patients receiving the treatment were three times more likely to achieve significant improvement in eczema severity, as measured by EASI and vIGA-AD scores, compared to those on placebo. Improvements continued beyond week 24, suggesting that the benefits strengthen over time."

P3 data • Atopic Dermatitis

A Phase 2, Dose Ranging Study Assessing Rocatinlimab in Moderate-to-severe Asthma (clinicaltrials.gov) - P2 | N=312 | Active, not recruiting | Sponsor: Amgen | Recruiting ➔ Active, not recruiting

Enrollment closed • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases

The OX40-OX40L Co-stimulatory pathway in dermatology: emerging frontiers for therapeutic approaches. (PubMed, Inflamm Res) - "The complex interplay between mast cells expressing OX40L and T cells expressing OX40, which in some contexts can inhibit regulatory T cell (Treg) function and promote Th17 differentiation, underscores the therapeutic potential of either antagonizing or agonizing this co-stimulatory pathway. In this review, we discuss selected dermatological diseases in which the OX40/OX40L axis appears relevant to their immunopathogenesis and may serve as a potential therapeutic target."

Journal • Review • Atopic Dermatitis • Dermatitis • Dermatology • Hidradenitis Suppurativa • Immunology • Oncology • Psoriasis • Urticaria • Vitiligo • CD8 • TNFSF4

Rocatinlimab Improves Patient-Reported Outcomes in Adults with Moderate-to-Severe Atopic Dermatitis: Results from a Double-Blind Placebo-Controlled Phase 2b Study. (PubMed, Dermatol Ther (Heidelb)) - P2 | "This analysis demonstrates the importance of characterizing the burden of moderate-to-severe AD from the patient's perspective, alongside clinical disease measures, to develop a fuller picture of treatment benefit."

Clinical • Journal • P2b data • Patient reported outcomes • Atopic Dermatitis • CNS Disorders • Dermatitis • Dermatology • Immunology • Pruritus • Pulmonary Disease • Respiratory Diseases • Sleep Disorder

A Phase 3, Placebo-controlled, Double-blind Study Assessing Rocatinlimab in Prurigo Nodularis (clinicaltrials.gov) - P3 | N=469 | Active, not recruiting | Sponsor: Amgen | Trial completion date: May 2027 ➔ Jan 2027 | Trial primary completion date: Feb 2027 ➔ Oct 2026 | Recruiting ➔ Active, not recruiting

Enrollment closed • Trial completion date • Trial primary completion date • Immunology • Prurigo Nodularis

ROCKET-ASTRO: A Study to Evaluate Rocatinlimab (AMG 451) in Adolescent Participants With Moderate-to-severe Atopic Dermatitis (AD) (clinicaltrials.gov) - P3 | N=532 | Active, not recruiting | Sponsor: Amgen | Trial primary completion date: Sep 2025 ➔ Feb 2025

Trial primary completion date • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

ROCKET-ASCEND: A Study to Assess Long-term Safety, Tolerability, and Efficacy of Rocatinlimab in Adult and Adolescent Participants With Moderate-to-severe Atopic Dermatitis (AD) (clinicaltrials.gov) - P3 | N=2621 | Active, not recruiting | Sponsor: Amgen | Recruiting ➔ Active, not recruiting

Enrollment closed • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

INHIBITION OF OX40 IN CD4+ T CELLS ATTENUATES HEPATIC INFLAMMATION IN A HUMAN EX VIVO MODEL OF METABOLIC DYSFUNCTION-ASSOCIATED STEATOHEPATITIS (AASLD 2025) - "Human precision-cut liver slices (PCLS) were incubated in a MASH-inducing media (GFIPO: glucose, fructose, insulin, oleate, palmitate ± TNFα) and treated with Rocatinlimab, an antagonistic anti-OX40 monoclonal antibody... In murine MASH, OX40 and OX40L were upregulated specifically in hepatic CD4+ T cells and monocyte-derived macrophages, respectively. Blocking OX40 in the human ex vivo MASH model reduced markers of inflammation, highlighting OX40 as a promising immunotherapeutic target to alleviate MASH."

IO biomarker • Preclinical • Fibrosis • Hepatology • Immunology • Inflammation • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • CCL2 • CD4 • CD8 • CXCL10 • FASN • IFNG • PTPRC • TNFSF4