vixarelimab (RG6536) / Kiniksa Pharmaceuticals, Roche - LARVOL DELTA

Prurigo nodularis enters the biologic era: what has changed and what vixarelimab still must prove. (PubMed, J Dermatolog Treat) - No abstract available

Journal • Immunology • Prurigo Nodularis

Roche drops $100M Kiniksa fibrosis drug from phase 2 pipeline as part of quarterly clearout (FierceBiotech) - "Roche has waved goodbye to a inflammation drug from Kiniksa Pharmaceuticals—as well as the $100 million that the pharma paid for the therapy—as part of a quarterly pipeline cleanout of underperforming assets....Genentech then took the drug into a phase 2 study in patients with idiopathic pulmonary fibrosis or systemic sclerosis-associated interstitial lung disease...However, Roche has now decided to abandon this program, explaining to Fierce Biotech this morning that a futility analysis had 'determined that the study was unlikely to achieve its efficacy objectives.'....'There were no new safety signals identified in this study,' according to a Roche spokesperson, who added that the company was 'disappointed' by the futility analysis."

Discontinued • P2 data • Idiopathic Pulmonary Fibrosis • Immunology • Interstitial Lung Disease • Systemic Sclerosis

A Study Evaluating the Efficacy and Safety of Vixarelimab in Participants With Idiopathic Pulmonary Fibrosis and in Participants With Systemic Sclerosis-Associated Interstitial Lung Disease (clinicaltrials.gov) - P2 | N=286 | Active, not recruiting | Sponsor: Genentech, Inc. | Recruiting ➔ Active, not recruiting | Trial completion date: Aug 2027 ➔ Jan 2026 | Trial primary completion date: Apr 2027 ➔ Jan 2026

Enrollment closed • Trial completion date • Trial primary completion date • Idiopathic Pulmonary Fibrosis • Immunology • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases • Scleroderma • Systemic Sclerosis

Vixarelimab Demonstrates Rapid, Sustained Clinical Benefits in Prurigo Nodularis (HCPLive) - "reatment with vixarelimab at the 16-week mark led to significantly increased mean WI-NRS score reductions compared with placebo across all dosing cohorts...Reductions were shown by the investigators to be as follows: -56.2% among those in the high-dose arm; -51.0% among those in the mid-dose arm; -33.0% among those the low-dose arm; -14.5% in the placebo arm...At least a 4-point reduction in WI-NRS scores was seen by Ständer et al in 31 66.0% of those on high-doses of the drug, 61.7% of those in the mid-dose arm, and 29.8% in the low-dose arm....38.3% of those in the high-dose cohort; 29.8% of those in the mid-dose cohort; 14.9% of those in the low-dose cohort; 10.4% of those in the placebo cohort."

P2b data • Prurigo Nodularis

Vixarelimab: NME submissions in US for IPF and systemic sclerosis associated interstitial lung disease in 2028 and beyond (Roche) - Q3 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

Divergent Oncostatin M receptor-driven pathways across fibrotic and inflammatory conditions (ERS 2025) - "Lung damage and fibrosis are reduced in Osm-/- mice and with OSM blocking mAbs in the bleomycin model. However, while OSMR+ stroma was observed across indications, ILD and IBD displayed marked differences in abundance (Fig1B) and profibrotic/proinflammatory phenotype (Fig1C) of these cells, suggesting tissue- and disease- specific responses to OSMR blockade. Vixarelimab, an anti-human OSMR antagonist, is currently in Ph2 trials for IPF, SSc-ILD and UC."

Fibrosis • Gastroenterology • Gastrointestinal Disorder • Inflammation • Inflammatory Bowel Disease • OSMR

Disease Severity and Pruritus Treatment Outcomes in Prurigo Nodularis: A Systematic Review of Randomized-Controlled Trials (CDA 2025) - "Treatments included nemolizumab (49.7%, 560/1127), serlopitant (31.1%, 351/1127), dupilumab (13.6%, 153/1127), nalbuphine (3.5%, 40/1127) and vixarelimab (2.0%, 23/1127). The greatest proportion of patients achieving IGA score of 0/1 compared to control was achieved by nemolizumab 0.5 mg/kg Q4W (67.6%; placebo 14.3%; n=70; duration 12-weeks), dupilumab 300 mg Q2W (48.0%; placebo 18.4%; n=151; duration 24-weeks) and nemolizumab 30-60 mg Q4W (31.9%; placebo 9.1%; n=560; duration 16-weeks). Conclusions Nemolizumab and dupilumab were the most effective at reducing itch and PN disease severity assessed by WI-NRS and IGA scores."

Clinical • Review • 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=79 | Terminated | Sponsor: Genentech, Inc. | Trial completion date: Feb 2028 ➔ Jun 2025 | Active, not recruiting ➔ Terminated | Trial primary completion date: Sep 2026 ➔ Jun 2025; Based on a futility analysis, which suggested that the Moonglow study was unlikely to meet its primary endpoint.

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

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

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

THERAPEUTIC BLOCKADE OF OSM/IL31R SIGNALING IN DSS-INDUCED COLITIS ACCELERATES WOUND HEALING BY REDUCING INFLAMMATORY FIBROBLAST ACTIVATION AND NEUTROPHIL RECRUITMENT (DDW 2025) - P2 | "Vixarelimab, an OSMRb blocking monoclonal antibody, is under evaluation as a therapeutic for IBD in a phase 2 study in ulcerative colitis (NCT06137183)... To pre-clinically evaluate the OSMR pathway as a target in IBD, we compared multiple murine models of colitis including Helicobacter hepaticus (Hh)+ anti-IL-10, Citrobacter rodentium infection, dextran sodium sulfate (DSS)-induced colitis, and a pinch biopsy model of wound healing to understand what models induce the OSM/IL31 pathway and best recapitulate features of human non-response. Histology, gene expression, and flow cytometry were utilized to understand which model best recapitulated the biology associated with non-response. We found that OSM was strongly induced in models that cause epithelial damage, such as DSS-induced colitis and the pinch biopsy model, but not in infectious models such as the Hh + anti-IL10 or C. rodentium model."

Gastroenterology • Gastrointestinal Disorder • Immunology • Infectious Disease • Inflammation • Inflammatory Bowel Disease • Ulcerative Colitis • CD123 • ICAM1 • IL10 • IL1R1 • IL31RA • IL6 • LIFR • OSMR

EVALUATING THE PHARMACODYNAMIC (PD) EFFECTS OF VIXARELIMAB IN PATIENTS WITH ULCERATIVE COLITIS (UC): DESIGN AND RATIONALE FOR A PHASE 1C STUDY (DDW 2025) - P2 | "These data support the rationale for the early time points chosen for the present study by providing evidence that changes in inflammatory fibroblasts may be identifiable earlier than the typical week 12 evaluation in IBD induction trials. Conclusion The evaluation of inflammatory fibroblasts in patients with UC through integration of OSMRβ occupancy assay and snRNA-seq enables assessment of mechanistic insights for first-in-class therapeutic targeting of the inflammatory fibroblast-myeloid cell axis by vixarelimab in UC."

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

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