rocatinlimab (KHK4083) / Kyowa Kirin, Amgen - LARVOL DELTA

Kyowa Kirin Announces Abstract Presentation at the European Academy of Dermatology and Venereology (EADV) Congress (PRNewswire) - "Kyowa Kirin Co., Ltd...today announced that results of the Phase 3 ROCKET IGNITE trial of rocatinlimab, an investigational therapy targeting the OX40 receptor (OX40R) in patients with moderate-to-severe atopic dermatitis (AD), will be presented at the European Academy of Dermatology and Venereology (EADV) 2025 Annual Meeting to be held in Paris, France from September 17-20, 2025."

P3 data • Atopic Dermatitis

Continuous-Time Markov Population PK/PD Modeling of Longitudinal EASI Categorical Score in Atopic Dermatitis Treated With Rocatinlimab, an Anti-OX40 Monoclonal Antibody. (PubMed, CPT Pharmacometrics Syst Pharmacol) - P1, P2 | "The PPK-PD model adequately described the time course and drug-related change in EASI score and was used to simulate various dosage regimens to predict the time course of EASI response. The identified parameters and drug-exposure relationship were considered to potentially support dose revisions and optimization for phase 3 trials in patients with moderate-to-severe AD that are utilizing a subcutaneous regimen with dosing every 4 weeks."

Journal • PK/PD data • 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=2200 | Recruiting | Sponsor: Amgen | Trial primary completion date: Jun 2025 ➔ May 2027

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

Rocatinlimab: “EASI-75 and vIGA-AD 0/1 Responses at Week 24”; Atopic dermatitis (Kyowa Hakko Kirin Pharma) - Kyowa Kirin rocatinlimab Update: “Depth of skin response for patients treated with rocatinlimab vs PBO continued to increase through Week 24”

P3 data • Atopic Dermatitis • Immunology

Rocatinlimab Significantly Improves Clinical Signs and Symptoms of Moderate-to-Severe Atopic Dermatitis by Specifically Reducing OX40R+ T-Cell Population Without Signs of Immunosuppression (EAACI 2025) - P3 | "Conclusion ROCA significantly improved clinical signs and symptoms of msAD (primary and AO analyses), reducing OX40R+ T cells while maintaining the overall T-cell population with no meaningful impact on infections. These data indicate clinical efficacy without signs of immunosuppression and support ROCA as a novel monotherapy option."

Clinical • IO biomarker • Late-breaking abstract • Atopic Dermatitis • Dermatitis • Immunology

A Study to Evaluate Bioavailability of Rocatinlimab Autoinjector and Vial in Healthy Participants (clinicaltrials.gov) - P1 | N=231 | Completed | Sponsor: Amgen | Active, not recruiting ➔ Completed

Trial completion • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

A novel anti-OX40 human monoclonal antibody that blocks OX40/OX40L signaling and depletes OX40+ T cells. (PubMed, Mar Life Sci Technol) - "Interestingly, we also found that the most potent anti-OX40 antibody drug in the clinical stage, KHK4083, binds to different OX40 amino-acid residues, including Asp74, Lys82, Asp117, Ser118, Tyr119, and Lys120. This divergence suggests that the novel monoclonal antibody JY007 holds promise as a potential therapeutic option for patients with atopic dermatitis and may find broad applications in the treatment of autoimmune diseases. The online version contains supplementary material available at 10.1007/s42995-025-00284-y."

IO biomarker • Journal • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Oncology • Napsin A • TNFSF4

Biologics targeting OX40 and OX40L for treatment of atopic dermatitis have distinct inhibitory binding mechanisms (SID 2025) - "Our results provide initial prediction and analysis of the epitopes of OX40 and OX40L targeted biologics emerging for AD treatment. Rocatinlimab and amlitelimab appear to directly inhibit OX40-OX40L interactions via steric occlusion, with amlitelimab also possibly inhibiting OX40L trimer formation, whereas telazorlimab more specifically disrupts a critical intermolecular interaction."

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

Skin transcriptome modulation in Japanese patients with atopic dermatitis treated with rocatinlimab, an anti-OX40 receptor antibody (SID 2025) - P2 | "Pronounced gene signatures modulated vs BL were related to Th1, Th2, Th17, and Th22 cells, and markers of tissue resident memory T cells and epidermal barrier function (Wk 52, all p<0.05). Rocatinlimab induced durable efficacy with acceptable safety and meaningful biomarker responses, demonstrating potential T-cell rebalancing in Japanese patients with msAD."

Clinical • IO biomarker • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Pruritus

Emerging Therapies in the Treatment of Prurigo Nodularis: Biological Therapy and Systematic Review of Literature. (PubMed, Dermatol Ther (Heidelb)) - "Targeted therapies are revolutionizing PN treatment. Integrating clinical efficacy, immunologic endotyping, and real-world data will be pivotal to optimizing therapeutic strategies, enhancing outcomes, and personalizing care in prurigo nodularis."

IO biomarker • Journal • Review • Dermatology • Eosinophilia • Immunology • Inflammation • Prurigo Nodularis • Pruritus • CD123 • IL13 • IL31RA • IL4

OX40/OX40L as a Therapeutic Target in Atopic Dermatitis: A Scoping Review. (PubMed, Biologics) - "Moreover, early basic and clinical research has shown encouraging results regarding the efficacy and safety of therapies targeting the OX40-OX40L axis in moderate-to-severe AD. Therefore, herein we aim to summarize the current evidence regarding the efficacy and safety of inhibiting the OX40/OX40L signaling axis in patients with moderate-to-severe AD."

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

Safety and Efficacy of Anti-OX40 Therapies in Atopic Dermatitis: A Systematic Review and Meta-Analysis. (PubMed, Dermatitis) - "We aimed to systematically evaluate the efficacy and safety of anti-OX40 therapies (amlitelimab, rocatinlimab, and telazorlimab) in moderate-to-severe AD. In conclusion, anti-OX40 therapies demonstrate clinically meaningful efficacy and an acceptable safety profile for moderate-to-severe AD, offering a potential alternative for patients with inadequate responses to current treatments. Further research is warranted to confirm these results and to refine optimal dosing strategies."

Clinical • Journal • Retrospective data • Review • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Inflammation

Investigating Efficacy of Atopic Dermatitis Systemic Therapeutics After Discontinuation Part I: Biologics. (PubMed, J Clin Aesthet Dermatol) - "Five clinical trial programs met our inclusion criteria, each investigating a different biologic: dupilumab, tralokinumab, lebrikizumab, amlitelimab, and rocatinlimab. The variability in eligibility criteria, treatment durations, and withdrawal periods across trials presents a major challenge in assessing biologics for AD, complicating the comparison of their sustained responses in the absence of head-to-head studies. This heterogeneity, combined with factors such as disease duration and prior use of systemic medications before trial enrollment, hampers the identification of key pathways in AD pathogenesis and impedes efforts to better understand and characterize the disease."

Journal • Review • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

AMGEN AND KYOWA KIRIN PROVIDE TOP-LINE RESULTS FROM ROCATINLIMAB PHASE 3 IGNITE STUDY IN ADULTS WITH MODERATE TO SEVERE ATOPIC DERMATITIS (PRNewswire) - P3 | 769 | ROCKET-IGNITE (NCT05398445) | Sponsor: Amgen | "The IGNITE study, which evaluated two dose strengths of rocatinlimab, met its co-primary endpoints and all key secondary endpoints, achieving statistical significance for both rocatinlimab dose strengths versus placebo...At week 24, 42.3% of patients in the higher dose group achieved ≥75% reduction from baseline in Eczema Area and Severity Index score (EASI-75), a 29.5% difference vs. placebo (p < 0.001). In the lower dose group, 36.3% of patients achieved EASI-75, a 23.4% difference vs. placebo (p < 0.001). In the higher dose group, 23.6% of patients achieved a validated Investigator's Global Assessment for Atopic Dermatitis (vIGA-AD™) score of 0 (clear) or 1 (almost clear) with a ≥2-point reduction from baseline (vIGA-AD 0/1) at week 24, representing a 14.9% difference vs. placebo (p < 0.001). In the lower dose group, 19.1% of patients achieved this endpoint, a 10.3% difference vs. placebo (p = 0.002)."

P3 data: top line • Atopic Dermatitis

The ROCKET program is also informed by the results of the SHUTTLE…studies. (PRNewswire) - P3 | N=746 | ROCKET-SHUTTLE (NCT05724199) | Sponsor: Amgen | "The SHUTTLE study...met its co-primary endpoints and all key secondary endpoints, achieving statistical significance for both rocatinlimab dose strengths plus TCS/TCI versus placebo plus TCS/TCI at week 24. For EASI-75, 52.3% of patients in SHUTTLE's higher dose group achieved the endpoint, a 28.7% difference vs. placebo (p < 0.001), while 54.1% of patients in the lower dose group achieved the endpoint, a 30.4% difference vs. placebo (p<0.001). For vIGA-AD 0/1, 26.1% of SHUTTLE patients in the higher dose group achieved the endpoint, a 13.8% difference vs. placebo (p<0.001). In the lower dose group, 25.8% of patients achieved the endpoint, a 13.5% difference vs. placebo (p<0.001). For rIGA 0/1, 23.3% of SHUTTLE patients in the higher dose group achieved the endpoint, an 11.5% difference vs. placebo (p<0.001). In the lower dose group, 22.7% of patients achieved the endpoint, a 10.9% difference vs. placebo (p = 0.002)."

P3 data • Atopic Dermatitis

Rocatinlimab Significantly Improved Clinical Signs and Symptoms by Targeting OX40R+ T cells in Patients with Moderate-to-Severe Atopic Dermatitis: Results from the Phase 3 ROCKET HORIZON Trial (AAD 2025) - No abstract available

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

ROCKET: a phase 3 program evaluating the efficacy and safety of rocatinlimab in moderate-to-severe atopic dermatitis. (PubMed, Immunotherapy) - P3 | "Rocatinlimab is a T-cell rebalancing therapy that inhibits and reduces pathogenic T cells by targeting the OX40 receptor. ROCKET, a large, global phase 3 program of eight clinical trials (NCT05398445; NCT05651711; NCT05724199; NCT05899816; NCT05704738; NCT05633355; NCT05882877; NCT06224192), will evaluate the efficacy, durability of response, and long-term safety of rocatinlimab as monotherapy and combination therapy in adult and adolescent patients with moderate-to-severe AD with or without prior exposure to biologics or systemic JAK inhibitors."

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

Kyowa Kirin Announces Late-Breaking Abstract Presentation at the American Academy of Dermatology Annual Meeting 2025 (PRNewswire) - "Kyowa Kirin...announced that results of the Phase 3 ROCKET HORIZON trial of rocatinlimab, an investigational therapy targeting the OX40 receptor (OX40R) in patients with moderate-to-severe atopic dermatitis (AD), will be presented at the American Academy of Dermatology (AAD) 2025 Annual Meeting to be held in Orlando, Florida from March 7-11, 2025."

Late-breaking abstract • P3 data • Atopic Dermatitis

Preclinical data supporting the differentiated profile of STAR-0310, a novel OX40 antagonistic monoclonal antibody (AAAAI-WAO 2025) - "Results STAR-0310 demonstrated an approximately 8-fold increase in binding affinity to human OX40 compared to telazorlimab...STAR-0310 induced significantly lower ADCC on activated T-cells and regulatory T-cells, compared to an in-house analogue of rocatinlimab (AMG451)...Conclusions These preclinical data support further development of STAR-0310 for the treatment of moderate-to-severe atopic dermatitis and other immunologic diseases. The extended half-life suggests potential for sustainable efficacy and prolonged suppression of disease symptoms."

Preclinical • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

Kyowa Kirin to Invest More Than 100 Billion Yen in Research and Development This Year [Google translation] (Chosun Biz) - "Japan's Kyowa Kirin announced that it plans to invest more than 100 billion yen in research and development this year....Kyowa Kirin announced that it invested 103.5 billion yen last year, a 44% increase from the previous year, and that it plans to make large-scale investments for the second consecutive year. The company explained, 'We plan to further advance the development pipeline that we are currently focusing on, centered around the human anti-OX40 antibody 'KHK4083' (rocatinlimab) targeting atopic dermatitis.'"

Financing • Atopic Dermatitis

Rocatinlimab: Data readout from P3 ROCKET-IGNITE trial (NCT05398445) for moderate-to-severe atopic dermatitis in Q2 2025 (Kyowa Hakko Kirin Pharma) - Q4 2024 Results: Data readout from P3 ROCKET-SHUTTLE trial (NCT05724199) for moderate-to-severe atopic dermatitis in Q2 2025

P3 data • Atopic Dermatitis • Immunology

Rocatinlimab: Data readout from P3 ROCKET-HORIZON trial (NCT05651711) for moderate-to-severe atopic dermatitis in H1 2025 (Kyowa Hakko Kirin Pharma) - Q4 2024 Results

P3 data • Atopic Dermatitis • Immunology

A Study to Evaluate Bioavailability of Rocatinlimab Autoinjector and Vial in Healthy Participants (clinicaltrials.gov) - P1 | N=231 | Active, not recruiting | Sponsor: Amgen | Recruiting ➔ Active, not recruiting

Enrollment closed • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

A Study Evaluating Rocatinlimab in Moderate-to-severe Atopic Dermatitis (ROCKET-IGNITE) (clinicaltrials.gov) - P3 | N=769 | Completed | Sponsor: Amgen | Active, not recruiting ➔ Completed

Monotherapy • Trial completion • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

Study to Investigate the Effect of Rocatinlimab (AMG 451) on the Pharmacokinetics of Multiple Cytochrome P450 (CYP450) Substrates in Participants With Moderate to Severe Atopic Dermatitis (clinicaltrials.gov) - P1 | N=21 | Completed | Sponsor: Amgen | Active, not recruiting ➔ Completed

Trial completion • Atopic Dermatitis • Dermatitis • Dermatology • Immunology