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

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

Generation of novel human anti-OX-40 mAbs endowed with different biological properties as tools for cancer therapy. (PubMed, Front Immunol) - "Moreover, epitope binning analyses show that they recognize distinct epitopes not overlapping with that of the clinically validated Rocatinlimab, thus they could become potential new therapeutic tools...We show here for the first time that NK cells express higher levels of a medium glycosylated OX-40 form than T cells, which is preferentially recognized by the novel mAbs but not by OX-40L, which instead binds to a highly glycosylated OX-40 variant absent on non-immune cells. Thus, glycosylation pattern could affect the recognition and biological effects of OX-40 binders and should be considered for the design of novel drugs."

IO biomarker • Journal • Oncology • TNFSF4

Rocatinlimab improved atopic dermatitis unresponsive to topical corticosteroids alone (Healio) - "Results showed both rocatinlimab arms achieved the coprimary endpoints of EASI 75 (52.3% of the 300 mg group and 54.1% of the 150 mg group vs. 23.5% of the placebo group; P < .001) and validated IGA-AD 0 or 1 (26.1% of the 300 mg group and 25.8% of the 150 mg group vs. 12.2% of the placebo group; P < .001) by week 24."

P3 data • Atopic Dermatitis

Outcomes Following Discontinuation of Systemic Immunomodulatory Therapies in Adults with Atopic Dermatitis: A Systematic Review (EADV 2025) - "Six studies examined biologic agents (amlitelimab, dupilumab (2 studies), tralokinumab, rezpegaldesleukin, rocatinlimab) and three evaluated JAK inhibitors (baricitinib, abrocitinib, upadacitinib). Emerging evidence suggests that sustaining disease control following discontinuation of systemic immunomodulatory therapy is possible in some adults with AD. Differences in outcomes between therapies may reflect variations in drug mechanisms or study design. To confidently identify individuals who may benefit from treatment discontinuation, further studies are required with harmonised outcomes (e.g."

Clinical • Immunomodulating • Review • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Infectious Disease

Outcomes Following Discontinuation of Systemic Immunomodulatory Therapies in Adults with Atopic Dermatitis: A Systematic Review (EADV 2025) - "Six studies examined biologic agents (amlitelimab, dupilumab (2 studies), tralokinumab, rezpegaldesleukin, rocatinlimab) and three evaluated JAK inhibitors (baricitinib, abrocitinib, upadacitinib). Emerging evidence suggests that sustaining disease control following discontinuation of systemic immunomodulatory therapy is possible in some adults with AD. Differences in outcomes between therapies may reflect variations in drug mechanisms or study design. To confidently identify individuals who may benefit from treatment discontinuation, further studies are required with harmonised outcomes (e.g."

Clinical • Immunomodulating • Review • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Infectious Disease

Online Education Significantly Improved Dermatologists' Knowledge Of The Mode Of Action And Key Clinical Data On Emerging Therapies For Atopic Dermatitis That Target The OX40-OX40 Ligand Pathway. (EADV 2025) - "Dermatologists significantly improved their knowledge of survival of pathogenic T cells as a key consequence of OX40-OX40L interaction in the pathogenesis of AD (17% pre- vs 43% post-activity; P <.001), the mode of action of amlitelimab and rocatinlimab (21% pre- vs 55% post-activity; P <.001) and clinical data for these novel therapies (54% pre- vs 74% post-activity; P <.001). This online activity significantly improved dermatologists' understanding of the role of the OX40-OX40L pathway in the pathogenesis of AD and of emerging biologic therapies targeting this pathway. Although there was significant knowledge improvement for all questions, the post test scores of 43% to 74% indicate that dermatologists would benefit from additional education to embed their knowledge of emerging biologic therapies targeting this pathway in AD."

Clinical data • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • TNFSF4

Efficacy and Safety of OX40-Receptor Targeting With Rocatinlimab in Moderate-to-Severe Atopic Dermatitis: Results From the Phase 3 ROCKET-Ignite Trial (EADV 2025) - P3 | "ROCKET-Ignite met its co-primary endpoints in a diverse treatment-experienced AD patient population. ROCA significantly improved AD clinical signs and symptoms with even greater efficacy observed in the All Data analyses regardless of RT and no indication of efficacy plateau at Wk 24 and was generally well tolerated. Along with the previously reported ROCKET-Horizon study, data from ROCKET-Ignite confirm the efficacy of ROCA monotherapy in adults with AD."

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

Rocatinlimab With Concomitant Topical Therapy Significantly Improved Clinical Signs and Symptoms of Atopic Dermatitis in Adults: Results From the Phase 3 ROCKET-SHUTTLE Trial (EADV 2025) - P3 | "ROCA combination therapy was well tolerated, and TEAEs were consistent with adult monotherapy studies. With the ROCKET-HORIZON and IGNITE monotherapy studies, ROCKET-SHUTTLE supports the efficacy and safety of ROCA administered with TCS/TCI."

Clinical • Late-breaking abstract • P3 data • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Infectious Disease • Pruritus