FDA Accepts Tirabrutinib NDA for Rare Brain Lymphoma Under Accelerated Approval Pathway
Key Insights
The FDA has accepted Deciphera Pharmaceuticals (search)' New Drug Application for tirabrutinib, a selective BTK inhibitor, to treat relapsed or refractory primary central nervous system lymphoma (search) under the accelerated approval pathway.
The regulatory submission is based on positive Phase 2 PROSPECT study results showing a 67% overall response rate and 44% complete response rate in patients with this rare and aggressive brain cancer.
If approved by the December 18, 2026 PDUFA date, tirabrutinib would become the first BTK inhibitor commercially available in the U.S. for treating this condition with limited therapeutic options.
The U.S. Food and Drug Administration has accepted for filing Deciphera Pharmaceuticals (search)' New Drug Application for tirabrutinib, a highly selective irreversible, second generation Bruton tyrosine kinase (search) inhibitor, for the treatment of relapsed or refractory primary central nervous system lymphoma (search) (R/R PCNSL) under the accelerated approval pathway. The FDA has set an action date of December 18, 2026, under the Prescription Drug User Fee Act.
Addressing Critical Unmet Medical Need
"R/R PCNSL is a rare and aggressive form of non-Hodgkin lymphoma (search) with particularly poor clinical outcomes. Patients often experience difficulty and delay in diagnosis, and once they are diagnosed, there is a high unmet need for a treatment with a favorable safety profile," said Matthew L. Sherman, M.D., Chief Medical Officer of Deciphera.
Primary central nervous system lymphoma (search) is a rare and aggressive extra-nodal non-Hodgkin lymphoma (search) that is confined to the brain parenchyma, spinal cord, eye, or leptomeninges without systemic involvement. The annual incidence rate of PCNSL is approximately five cases per 1,000,000 people in the U.S., with rates potentially increasing among immunocompromised individuals aged 65 years and older.
Strong Clinical Trial Results Drive Regulatory Submission
The NDA is supported by positive results from the Phase 2 PROSPECT study, presented at the 2025 American Society for Clinical Oncology Annual Meeting. In this trial, tirabrutinib demonstrated an overall response rate of 67%, a complete response rate of 44%, and a manageable safety profile.
The clinical need for effective treatments in this patient population is substantial. Despite recent progress in newly diagnosed patients with PCNSL after induction treatment, approximately 20 to 30 percent of patients are refractory to initial treatment, and up to 60 percent of patients will eventually relapse.
Potential First-in-Class Treatment Option
If approved, tirabrutinib will be the first BTK inhibitor therapy commercially available in the U.S. for the treatment of patients with R/R PCNSL, and the third commercial therapy for the Ono group available in the U.S. The study is currently recruiting patients with R/R PCNSL in a global Phase 3 randomized trial, which will serve as a confirmatory study for this indication.
Mechanism of Action and International Approvals
Tirabrutinib, discovered and developed by Ono Pharmaceutical Co., Ltd. (search), is a highly potent selective BTK inhibitor. Signaling through the B-cell receptor (search) regulates cellular proliferation and activation, and promotes survival, differentiation, and clonal expansion of B-cells. The BCR signaling pathway plays an important role in a number of B-cell malignancies.
The drug has already gained regulatory approval in several international markets. In Japan, tirabrutinib was approved in March 2020 for the treatment of R/R PCNSL and launched under the tradename of Velexbru® in May 2020. It was subsequently approved for the treatment of Waldenstrom macroglobulinemia (search) and lymphoplasmacytic lymphoma (search) in August 2020. Tirabrutinib was approved for the treatment of R/R PCNSL in South Korea in November 2021 and in Taiwan in February 2022.
Strategic Milestone for Global Expansion
"We are very pleased that the NDA for tirabrutinib has been accepted for filing," said Toichi Takino, President and COO of Ono Pharmaceutical Co., Ltd. (search) "This is an important milestone on the way to expanding our commercial pipeline and achieving our goal of becoming a global specialty pharma. Tirabrutinib's potential to address unmet patient needs embodies our corporate philosophy and we will continue to focus on developing and delivering innovative medicines to benefit patients worldwide."
The complex symptom profile of PCNSL varies depending on the neuroanatomical site of the lesion, and includes cranial neuropathy, neuropsychiatric symptoms, symptoms associated with increased intracranial pressure, seizures, ocular symptoms, headache, dysmotility, cranial neuropathy, and radiculopathy. There is a high unmet need for a treatment with a favorable safety profile, and data guiding therapeutic approaches are very limited.