vixarelimab (RG6536) / Kiniksa, Roche - LARVOL DELTA

Discovery of Divergent Oncostatin M Receptor-driven Pathways Across Fibrotic and Inflammatory Conditions (ATS 2025) - "Lung damage and fibrosis are reduced in Osm-/- mice as well as WT mice treated with OSM blocking mAbs in the bleomycin model of lung injury, inflammation and fibrosis. Vixarelimab, an anti-human OSMR antagonist, is currently being tested in the clinic for SSc-ILD, IPF and UC. Acknowledgements: The authors would like to acknowledge the Mark S. Wilson lab for their contributions to this research."

Late-breaking abstract • Fibrosis • Gastroenterology • Gastrointestinal Disorder • Idiopathic Pulmonary Fibrosis • Inflammation • Inflammatory Bowel Disease • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases • Scleroderma • Systemic Sclerosis • IL6 • OSMR

Baseline Characteristics of Idiopathic Pulmonary Fibrosis and Systemic-sclerosis-associated Interstitial Lung Disease Patients Enrolled in the Moonscape Study of Vixarelimab (ATS 2025) - P2 | "RESULTS As of 13-Sep-2024, 149 and 22 patients were randomized into Cohort 1 (IPF) and Cohort 2 (SSc-ILD), respectively, of which 44.3% were on antifibrotics (Cohort 1) and 27.3% were on nintedanib or tocilizumab (Cohort 2) at baseline. CONCLUSIONS Moonscape will provide evidence for the efficacy and safety of vixarelimab in patients with IPF and SSc-ILD. Interim patient baseline data indicates enrollment of patients with clinical and demographic characteristics that are reflective of IPF and SSc-ILD real-world populations."

Clinical • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Inflammation • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases • Scleroderma • Systemic Sclerosis • OSMR

New and Emerging Biologics and Jak Inhibitors for the Treatment of Prurigo Nodularis: A Narrative Review. (PubMed, Medicina (Kaunas)) - "Among new treatment options, dupilumab, an IL-4 receptor antagonist, and nemolizumab, an IL-31 receptor inhibitor, demonstrated significant efficacy in reducing pruritus and lesion severity in PN patients. Other promising monoclonal antibodies include vixarelimab (OSMRβ inhibitor) and barzolvolimab (KIT inhibitor). Small molecules such as JAK inhibitors (upadacitinib, povorcitinib) also show potential by modulating inflammatory pathways...Emerging biologics and small molecules represent a transformative approach for PN management, offering targeted therapies that address underlying immunological and neurological mechanisms. Ongoing research and long-term studies are crucial to optimizing treatment strategies and improving patient outcomes."

Journal • Review • Dermatology • Immunology • Prurigo Nodularis • Pruritus • IL4

A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Vixarelimab in Participants With Moderate to Severe Ulcerative Colitis (UC) (clinicaltrials.gov) - P2 | N=79 | Active, not recruiting | Sponsor: Genentech, Inc. | N=210 ➔ 79

Enrollment change • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Vixarelimab: NME submissions in US for IPF and systemic sclerosis associated interstitial lung disease in 2028 and beyond (Roche) - Q1 2025 Results: Regulatory submissions in EU for IPF and systemic sclerosis associated interstitial lung disease in 2028 and beyond

EMA filing • FDA filing • Idiopathic Pulmonary Fibrosis • Scleroderma

A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Vixarelimab in Participants With Moderate to Severe Ulcerative Colitis (UC) (clinicaltrials.gov) - P2 | N=210 | Active, not recruiting | Sponsor: Genentech, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

A Study to Evaluate the Activity, and Safety of Vixarelimab in Participants With Moderate to Severe Active Ulcerative Colitis (clinicaltrials.gov) - P1/2 | N=24 | Recruiting | Sponsor: Genentech, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Vixarelimab in Participants With Moderate to Severe Ulcerative Colitis (UC) (clinicaltrials.gov) - P2 | N=210 | Recruiting | Sponsor: Genentech, Inc. | Trial completion date: Feb 2027 ➔ Feb 2028 | Trial primary completion date: May 2026 ➔ Sep 2026

Trial completion date • Trial primary completion date • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

EVALUATING THE PHARMACODYNAMIC (PD) EFFECTS OF VIXARELIMAB IN PATIENTS WITH ULCERATIVE COLITIS (UC): DESIGN AND RATIONALE FOR A PHASE 1C STUDY (DDW 2025) - No abstract available

Clinical • PK/PD data • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Design and rationale for the phase 1c study evaluating the pharmacodynamic (PD) effects of vixarelimab in patients with Ulcerative Colitis (UC) (ECCO-IBD 2025) - P2 | "These data provide evidence that changes in inflammatory fibroblasts may be identifiable earlier than the typical week 12 evaluation in IBD induction trials providing rationale for the early time points chosen for the present study. Conclusion Integrating OSMRβ occupancy assay and snRNA-seq informs on assessment of inflammatory fibroblasts in patients with UC, enabling mechanistic insights for first-in-class therapeutic targeting of the inflammatory fibroblast-myeloid cell axis by vixarelimab in UC."

Clinical • PK/PD data • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis • OSMR

Vixarelimab: Regulatory submissions in US/EU for IPF in 2027 and beyond (Roche) - FY2024 Results

EMA filing • FDA filing • Idiopathic Pulmonary Fibrosis

A Study to Evaluate the Activity, and Safety of Vixarelimab in Participants With Moderate to Severe Active Ulcerative Colitis (clinicaltrials.gov) - P1/2 | N=24 | Not yet recruiting | Sponsor: Genentech, Inc. | Phase classification: P1 ➔ P1/2

Phase classification • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Vixarelimab in Participants With Moderate to Severe Ulcerative Colitis (UC) (clinicaltrials.gov) - P2 | N=210 | Recruiting | Sponsor: Genentech, Inc. | Trial primary completion date: Sep 2026 ➔ May 2026

Trial primary completion date • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

A Study to Evaluate the Activity, and Safety of Vixarelimab in Participants With Moderate to Severe Active Ulcerative Colitis (clinicaltrials.gov) - P1 | N=24 | Not yet recruiting | Sponsor: Genentech, Inc.

New P1 trial • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Therapies for Chronic Spontaneous Urticaria: Present and Future Developments. (PubMed, Pharmaceuticals (Basel)) - "If symptoms persist despite this adjustment, the next step involves the use of omalizumab, a monoclonal anti-IgE antibody, which has shown efficacy in the majority of cases. However, a subset of patients remains refractory, necessitating alternative treatments such as immunosuppressive agents like cyclosporine or azathioprine...Among them, significant attention is being given to drugs that block Bruton's tyrosine kinase (BTK), such as remibrutinib, which reduces mast cell activation. Therapies like dupilumab, which target the interleukin-4 (IL-4) and IL-13 pathways, are also under investigation. Additionally, molecules targeting the Mas-related G protein-coupled receptor X2 (MRGPRX2), and those inhibiting the tyrosine kinase receptor Kit, such as barzolvolimab, show promise in clinical studies...Further research is essential to better elucidate the pathophysiology of CSU and optimize treatment protocols to achieve long-term benefits in managing this condition...."

Journal • Review • Cardiovascular • Chronic Spontaneous Urticaria • Dermatology • Immunology • Urticaria • BTK • IL13 • IL4

The role of IL-31 and its inhibitors in treating pruritus (EADV 2024) - "Anti-IL-31 antibody, nemolizumab, in four clinical trials with a total of 684 participants, showed significant improvement in pruritus, illustrated by the pruritus visual analogue scale (VAS) demonstrating downward trend, and changes in EASI score for AD patients and PP-NRS for PN patients...Moreover, in a different study involving 49 patients with prurigo nodularis (PN) , vixarelimab was administered... Interleukin-31 appears to play a significant role in pruritis induction, and cell-type-specific contributions of IL-31R to itch, its expression mechanism and the downstream signaling pathway to induce itch should be further investigated. As of now inhibition of IL-31 by targeting the IL-31/IL31RA/OSMR β axis suggests the improvement in pruritus, sleep quality, and overall, quality of life of patients suffering from pruritic disorders and appears to be a promising treatment option for such illnesses."

Allergic Rhinitis • Dermatology • Immunology • Inflammation • Prurigo Nodularis • Pruritus • Psoriasis • CD123 • IL1R1 • IL31RA • OSMR

Vixarelimab: Regulatory submissions in US/EU for IPF in 2027 and beyond (Roche) - Q2 2024 Results

EMA filing • FDA filing • Idiopathic Pulmonary Fibrosis

Targeted Biologic Therapies in Chronic Prurigo: The Evolving Landscape of Chronic Prurigo Treatment. (PubMed, Curr Pharm Des) - No abstract available

Journal • Immunology • Prurigo Nodularis

ELEVATED OSM/OSMR EXPRESSION IN INFLAMED MUCOSAL TISSUE REFLECTS AN INFLAMMATORY CASCADE MEDIATED BY NEUTROPHIL:STROMAL INTERACTIONS ASSOCIATED WITH RESIDUAL DISEASE IN TREATMENT-REFRACTORY UC PATIENTS (DDW 2024) - P2 | "Additionally, we evaluated OSM/OSMR expression changes following treatment with etrolizumab and adalimumab to understand the specificity of these changes and their relationship to treatment response. Blockade of OSMR to decrease pro-inflammatory mediators of inflammatory fibroblasts and dampen the inflammatory cycle in UC is a viable strategy for achieving benefits in clinical disease. Vixarelimab, an OSMR-targeted monoclonal antibody that blocks OSM/OSMR signaling, is currently in Ph2 clinical development for UC (NCT06137183)."

Clinical • Residual disease • Stroma • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • CHI3L1 • CXCL5 • CXCL6 • CXCL8 • OSMR • PDGFRA • THY1

Chronic Prurigo. (PubMed, J Dtsch Dermatol Ges) - "Dupilumab is the first approved therapy for moderate and severe CNPG to date from the European Medicines Agency (EMA) and the US Food & Drug Administration (FDA). It also highlights other agents currently being studied in Phase II and Phase III clinical, randomized, placebo-controlled trials. These include biologics such as nemolizumab (anti-IL-31-RA-mAb), vixarelimab/KPL-716 (anti-Oncostatin-M receptor β-mAb), and barzolvolimab/CDX-0159 (anti-KIT-mAb), as well as Janus kinase inhibitors such as povorcitinib/INCB054707 and abrocitinib, and opioid modulators such as nalbuphine."

Journal • CNS Disorders • Dermatology • Immunology • Prurigo Nodularis • Pruritus • Rheumatoid Arthritis • OSMR

Biologic and Oral Small Molecule Treatment for Prurigo Nodularis: An Evidence-Based Review (AAD 2024) - "The most common biologic or small molecules utilized were: dupilumab (80.8%, 374/463), nemolizumab (7.3%, 34/463), vixarelimab (5%, 23/463), tofacitinib (2.6%, 12/463), and apremilast (2.4%, 11/463). These results indicate dupilumab and tofacitinib may be efficacious and safe agents for clearance of PN with nemolizumab and vixarelimab being additional options for reduction of pruritus. Larger-scale studies are warranted."

Review • Immunology • Infectious Disease • Prurigo Nodularis • Pruritus • Respiratory Diseases

A systematic review of interleukin-31 inhibitors in the treatment of prurigo nodularis. (PubMed, Inflammopharmacology) - "IL-31 inhibitors suggest distinct advantages in improving pruritus, sleep quality, and overall quality of life in subjects with moderate-to-severe PN. Further clinical studies are recommended to compare the effectiveness of these biologics to other therapeutic choices."

Journal • Review • CNS Disorders • Dermatology • Immunology • Prurigo Nodularis • Pruritus • Sleep Disorder

A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Vixarelimab in Participants With Moderate to Severe Ulcerative Colitis (UC) (clinicaltrials.gov) - P2 | N=210 | Recruiting | Sponsor: Genentech, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

KPL-716-C201: Study to Assess the Efficacy, Safety, and Tolerability of Vixarelimab in Reducing Pruritus in Prurigo Nodularis (clinicaltrials.gov) - P2 | N=190 | Completed | Sponsor: Kiniksa Pharmaceuticals, Ltd. | Phase classification: P ➔ P2

Phase classification • Dermatology • Immunology • Prurigo Nodularis • Pruritus

A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Vixarelimab in Participants With Moderate to Severe Ulcerative Colitis (UC) (clinicaltrials.gov) - P2 | N=210 | Not yet recruiting | Sponsor: Genentech, Inc.

New P2 trial • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis