Tirabrutinib could become first BTK inhibitor for U.S. patients with relapsed CNS lymphoma

The FDA accepted filing for a new drug application (NDA) today for tirabrutinib for the treatment of adults with relapsed or refractory primary central nervous system lymphoma (R/R PCNSL), according to an announcement from Deciphera Pharmaceuticals, a member of Ono Pharmaceutical Co. The agency is reviewing the application under an accelerated approval and has assigned a Prescription Drug User Fee Act (PDUFA) target action date of Dec. 18, 2026.

Tirabrutinib, marketed internationally under the brand name Velexbru, was developed by Ono Pharmaceutical and is an oral Bruton’s tyrosine kinase (BTK) inhibitor used to treat specific blood cancers. If approved in the U.S. for R/R PCNSL, it would become the first BTK inhibitor commercially available in the U.S. for this patient population and the third commercial therapy for the Ono group available in the country.

R/R PCNSL is a rare and aggressive form of non-Hodgkin lymphoma that is around the brain, spinal cord, or eyes without systemic involvement. The disease has an annual incidence rate of about five cases per 1 million people in the U.S., and incidence increases among immunocompromised individuals aged 65 years and older.

According to Deciphera, patients with PCNSL usually present symptoms that vary based on the location of the lesion in the central nervous system. These may include cranial neuropathy, neuropsychiatric symptoms, increased intracranial pressure, seizures, ocular symptoms, headache, dysmotility and radiculopathy.

Although there are advances in induction treatment for newly diagnosed patients, outcomes remain challenging. Roughly 20% to 30% of patients are refractory to initial treatment and up to 60% will eventually relapse, highlighting the high unmet need for additional therapies.

The NDA submission is supported by results from the phase 2 PROSPECT study, which were presented at the 2025 American Society for Clinical Oncology (ASCO) meeting. In the study, tirabrutinib demonstrated an overall response rate of 67% and a complete response rate of 44%. The company also reported that the therapy showed a manageable safety profile.

According to its clinical trial record, the phase 2 study began around June 2021 and likely concluded in 2025. It was conducted in 39 locations across the U.S., allowing researchers to evaluate tirabrutinib in patients with relapsed or refractory PCNSL at multiple centers nationwide.

“R/R PCNSL is a rare and aggressive form of non-Hodgkin lymphoma with particularly poor clinical outcomes,” Matthew L. Sherman, M.D., chief medical officer of Deciphera, said in the news release. “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.”

The application is being reviewed under the accelerated approval pathway, which allows earlier approval of drugs that treat serious conditions and fill an unmet medical need based on a surrogate endpoint. As part of this accelerated approval process, a global phase 3 randomized trial is currently recruiting patients with R/R PCNSL and is intended to serve as a confirmatory study for the indication.

Deciphera shared that tirabrutinib targets BTK, a key component in the B-cell receptor pathway, which helps control how B cells grow, activate and survive. It also plays a crucial role in several B-cell cancers, including PCNSL.

Tirabrutinib has already received approvals in countries outside the U.S., including Japan, which was approved in March 2020 for the treatment of R/R PCNSL and was launched under the tradename Velexbru in May 2020. It was later approved in Japan for Waldenstrom macroglobulinemia and lymphoplasmacytic lymphoma in August 2020. Tirabrutinib was also approved for R/R PCNSL in South Korea in November 2021 and in Taiwan in February 2022.