The U.S. Food and Drug Administration has accepted the New Drug Application for Velexbru (tirabrutinib), a BTK inhibitor, to treat relapsed or refractory primary central nervous system lymphoma (PCNSL). PCNSL is a rare and aggressive type of non-Hodgkin lymphoma that affects the brain and central nervous system.
The application is based on results from the Phase 2 PROSPECT study. In patients whose disease had returned or did not respond after high-dose methotrexate treatment, tirabrutinib showed strong activity. The overall response rate was 67%, and 44% of patients achieved a complete response. Patients responded quickly, with a median time to response of 1 month. The median duration of response was 9.3 months, and median progression-free survival was 6 months.
The drug was generally manageable in terms of safety. Common side effects included fatigue, anemia, low lymphocyte counts, headache, diarrhea, and falls. Serious treatment-related side effects occurred in 44% of patients. Cardiac events were uncommon (under 10%) and were mild. The study included patients with a median age of 65.5 years, all previously treated with methotrexate, and nearly half had refractory disease. Patients received 480 mg of tirabrutinib orally once daily. A Phase 3 confirmatory trial, NCT07104032, is now recruiting to compare tirabrutinib with rituximab plus temozolomide.