At a Glance
- NDA accepted under accelerated approval for R/R PCNSL; PDUFA date set for December 18, 2026.
- PROSPECT study shows 67% ORR, 44% CR, and manageable safety in R/R PCNSL patients.
- First BTK inhibitor for R/R PCNSL if approved in U.S.; already launched as VELEXBRU® in Japan, South Korea, Taiwan.
- Phase 3 confirmatory study recruiting (NCT07104032) to support accelerated approval.
Written By: Samiksha Jadhav BPharm
Reviewed By: Pharmacally Editorial Team
Osaka-based Ono Pharmaceutical Co., Ltd. Announced today: the U.S. Food and Drug Administration (FDA) has accepted the New Drug Application (NDA) for tirabrutinib under the accelerated approval pathway. This highly selective, irreversible second-generation Bruton’s tyrosine kinase (BTK) inhibitor targets relapsed or refractory primary central nervous system lymphoma (R/R PCNSL), a rare and aggressive non-Hodgkin lymphoma with dismal outcomes.
The FDA has assigned a Prescription Drug User Fee Act (PDUFA) action date of December 18, 2026, signaling potential U.S. approval within the year.
If greenlit, tirabrutinib (VELEXBRU® in approved markets) would mark Ono’s third U.S. commercial therapy and the first BTK inhibitor for R/R PCNSL in the country.
Strong Phase 2 Data Fuels Optimism
The NDA draws from the Phase 2 PROSPECT study, unveiled at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting. Tirabrutinib delivered an overall response rate (ORR) of 67% and a complete response (CR) rate of 44%, paired with a manageable safety profile. These results highlight its potential to fill a critical gap in R/R PCNSL care, where 20-30% of patients resist initial therapy and up to 60% relapse.
A global Phase 3 randomized trial (ClinicalTrials.gov NCT07104032) is now recruiting to confirm these findings, aligning with FDA accelerated approval requirements.
“R/R PCNSL is a rare and aggressive form of non-Hodgkin lymphoma with particularly poor clinical outcomes,” noted Matthew L. Sherman, M.D., Chief Medical Officer at Deciphera Pharmaceuticals. “Patients often face delayed diagnosis and a high unmet need for treatments with favorable safety.”
Ono President and COO Toichi Takino echoed the excitement: “This is an important milestone toward expanding our commercial pipeline and becoming a global specialty pharma. Tirabrutinib embodies our philosophy of delivering innovative medicines worldwide.”
Tirabrutinib: Proven Track Record in Asia
Discovered and developed by Ono, tirabrutinib disrupts B-cell receptor (BCR) signaling to curb B-cell malignancies. In Japan, it gained approval for R/R PCNSL in March 2020 (launched as VELEXBRU® in May), followed by Waldenstrom macroglobulinemia and lymphoplasmacytic lymphoma in August 2020. Approvals followed in South Korea (November 2021) and Taiwan (February 2022) for R/R PCNSL.
The Burden of PCNSL
Primary central nervous system lymphoma (PCNSL) is an extra-nodal non-Hodgkin lymphoma limited to the brain, spinal cord, eyes, or leptomeninges, without systemic spread. U.S. incidence hovers at about 5 cases per million annually, rising in immunocompromised individuals over 65. Symptoms vary by lesion site ranging from headaches and seizures to cranial neuropathy and neuropsychiatric issues but data on optimal therapies remains scarce. For more on R/R PCNSL, visit navigatingpcnsl.com.
This FDA filing underscores Ono’s push into global oncology, potentially transforming options for R/R PCNSL patients.
Reference
Ono Announces U.S. Food and Drug Administration Acceptance for Filing of New Drug Application for Tirabrutinib in Patients with Relapsed or Refractory PCNSL, 16 February 2026, https://www.ono-pharma.com/en/news/20250216.html
ONO PHARMA Presents Positive Results from Pivotal Trial in U.S. Patients with Relapsed or Refractory PCNSL at 2025 ASCO Annual Meeting, 28 May 2026, https://www.ono-pharma.com/en/news/20250528.html
Study of Tirabrutinib vs Rituximab/Temozolomide for Relapsed/Refractory Primary Central Nervous System Lymphoma (PCNSL), ClinicalTrials.gov ID NCT07104032, https://clinicaltrials.gov/study/NCT07104032