Velexbru (tirabrutinib)

P2, N=119, Active, not recruiting, Ono Pharmaceutical Co. Ltd | Trial primary completion date: Mar 2027 --> Jan 2026

P3, N=132, Recruiting, Ono Pharmaceutical Co. Ltd | Not yet recruiting --> Recruiting

P3, N=132, Not yet recruiting, Ono Pharmaceutical Co. Ltd | Initiation date: Nov 2025 --> Feb 2026

Our in vitro data demonstrate that tirabrutinib influences daunorubicin pharmacodynamics by targeting both metabolic and transport pathways. However, Chou - Talalay analysis highlights the importance of appropriate dosing to achieve therapeutic synergy in combination regimens.

Historically, high-dose methotrexate- or cytarabine-based chemotherapy, intrathecal therapy, and radiotherapy have been used; however, responses varied, and toxicity was considerable...Retrospective data support durable responses with ibrutinib, tirabrutinib, and zanubrutinib, while early findings suggest that non-covalent BTK inhibitors expand options for relapsed or refractory cases. Herein, we synthesize current evidence on epidemiology, pathophysiology, and diagnostic work-up. We also outline therapeutic recommendations integrating the genotype, disease pattern, and patient fitness and conclude with unmet needs and future directions.

P2, N=119, Active, not recruiting, Ono Pharmaceutical Co. Ltd | Recruiting --> Active, not recruiting

P1, N=32, Recruiting, Ono Pharmaceutical Co. Ltd | Not yet recruiting --> Recruiting | N=24 --> 32 | Initiation date: Jan 2026 --> Oct 2025

P1, N=24, Not yet recruiting, Ono Pharmaceutical Co. Ltd

Despite initial partial remission with corticosteroids and cyclosporine, neurological symptoms emerged alongside nephrotic syndrome relapse two years after onset...After bendamustine-rituximab therapy showed partial effectiveness, tirabrutinib, a Bruton tyrosine kinase inhibitor, achieved complete remission of both renal and neurological manifestations with sustained response over three years. Immunofluorescence staining revealed increased nuclear factor (NF)-κB and STAT3 expression in infiltrating immune cells and elevated NF-κB in surrounding tubular epithelial cells, suggesting activation of these pathways downstream of the MYD88 mutation in kidney pathology. Our findings suggest a potential contribution of Bruton's tyrosine kinase signaling to both kidney and neurological pathology in Bing-Neel syndrome, with tirabrutinib achieving clinical improvement in both organ manifestations.

P3, N=132, Not yet recruiting, Ono Pharmaceutical Co. Ltd

P1, N=20, Active, not recruiting, Ono Pharmaceutical Co. Ltd | Recruiting --> Active, not recruiting

Tirabrutinib's selective BTK inhibition may activate cytotoxic CD8+ T cells, contributing to Stevens-Johnson syndrome/TEN pathogenesis. Further studies are needed to clarify the mechanisms and develop better diagnostic approaches for BTK inhibitor-related drug eruptions.