FDA Accepts New Drug Application for BTK Inhibitor Tirabrutinib

The FDA has accepted the new drug application (NDA) for tirabrutinib (ONO-4059), a highly selective, irreversible, second-generation Bruton tyrosine kinase (BTK) inhibitor developed for the treatment of patients with relapsed or refractory primary central nervous system lymphoma (R/R PCNSL).¹

The application is being reviewed under the FDA’s accelerated approval pathway, with a designated Prescription Drug User Fee Act (PDUFA) action date of December 18, 2026. If approved, tirabrutinib would become the first BTK inhibitor commercially available in the United States for this specific patient population, addressing a critical unmet medical need for a rare and aggressive form of non-Hodgkin lymphoma (NHL).

“R/R PCNSL is a rare and aggressive form of [NHL] 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, MD, chief medical officer of Deciphera, in a news release. “The FDA’s acceptance of tirabrutinib’s NDA for filing is an exciting milestone as it brings us one step closer to our goal of providing patients with R/R PCNSL an important new treatment option.”

Mechanism of Action of Tirabrutinib

As a highly potent selective BTK inhibitor, tirabrutinib targets the B-cell receptor (BCR) signaling pathway. BCR signaling is essential for the proliferation, activation, survival, differentiation, and clonal expansion of B cells. Because the BCR pathway is critical to various B-cell malignancies, inhibiting BTK serves to disrupt the progression of the disease.

Clinical Trial Results

The NDA submission is primarily supported by positive data from the phase 2 PROSPECT study (NCT04947319),² which was presented at the 2025 American Society for Clinical Oncology (ASCO) Annual Meeting.

In the PROSPECT study, a 67% overall response rate was observed, and a 44% complete response rate was observed. The safety profile was manageable. At the data cut off, 13 patients (27%) remained on tirabrutinib. Patients discontinued treatment due to disease progression (54.2%) and death (8.3%). One patient discontinued treatment due to an adverse event (AE). The most common AEs experienced were anemia, maculopapular rash, fatigue, neutrophil count decrease, lymphocyte count decrease, pruritus, and rash.³

To support the accelerated approval pathway, a global phase 3 randomized trial (NCT07104032)⁴ is currently recruiting patients. This study is designed to serve as the confirmatory trial to verify the clinical benefit of tirabrutinib in the R/R PCNSL indication.

Tirabrutinib is already established in several international markets under the tradename Velexbru:

• Japan: Approved in March 2020 for R/R PCNSL; subsequently approved for Waldenstrom macroglobulinemia and lymphoplasmacytic lymphoma in August 2020.
• South Korea: Approved for R/R PCNSL in November 2021.
• Taiwan: Approved for R/R PCNSL in February 2022.

“We are very pleased that the NDA for tirabrutinib has been accepted for filing,” said Toichi Takino, president and chief operating officer of Ono Pharmaceutical Co, in a news release.¹ “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.”

REFERENCES

1.Deciphera Pharmaceuticals announces U.S. Food and Drug Administration acceptance for filing of new drug application for tirabrutinib in patients with relapsed or refractory PCNSL. News release. Deciphera Pharmaceuticals. Published and accessed February 17, 2026. https://tinyurl.com/mwvndjkw

2.Study of tirabrutinib (ONO-4059) in patients with primary central nervous system lymphoma (PROSPECT Study). ClinicalTrials.gov. Updated October 24, 2025. Accessed February 17, 2026. https://clinicaltrials.gov/study/NCT04947319

3.ONO Pharma presents positive results from pivotal trial in U.S. patients with relapsed or refractory PCNSL at 2025 ASCO Annual Meeting. News release. Deciphera. Published May 28, 2025. Accessed February 17, 2026. https://tinyurl.com/ywh23sae

4.Study of tirabrutinib vs rituximab/temozolomide for relapsed/refractory primary central nervous system lymphoma (PCNSL). ClinicalTrials.gov. Updated February 4, 2026. Accessed February 17, 2026. https://clinicaltrials.gov/study/NCT07104032