Eli Lilly announced FDA approval of Jaypirca (pirtobrutinib, 100 mg & 50 mg tablets) for the treatment of adults with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) previously treated with a covalent BTK inhibitor on December 3rd, 2025. This action converts an accelerated approval from December 2023 into a full approval.
FDA approval of pirtobrutinib was based on results from BRUIN CLL-321, according to a company press release. BRUIN is a Phase III clinical trial evaluating pirtobrutinib versus the investigator’s choice of two other treatments in BTK inhibitor pre-treated patients with R/R CLL or SLL. Median progression-free survival, the study’s primary endpoint, was 14 months in patients treated with pirtobrutinib versus 8.7 months in patients given the other treatments.
According to the release, pirtobrutinib is the first and only FDA-approved non-covalent BTK inhibitor. Prior to this approval, FDA also granted accelerated approval to pirtobrutinib for patients with R/R mantle cell lymphoma who had at least two lines of systemic therapy, including a BTK inhibitor.
“This label expansion allows physicians to use [pirtobrutinib] directly after a covalent BTK inhibitor, the setting where we have always believed it has its most unique potential impact for patients,” said Jacob Van Naarden, Executive Vice President, President, Lilly Oncology, in the release. “With robust efficacy and safety evidence from the only study of its kind in the post-covalent BTK inhibitor treatment setting, we’re proud to now offer this therapy to more patients with CLL or SLL at an earlier stage of their treatment plan.”
“Pirtobrutinib is the only medicine in CLL or SLL that has been prospectively studied in a randomized trial of patients previously treated with a covalent BTK inhibitor, and I am excited to see this expanded FDA approval recognize the benefit it can deliver to this broader group of patients,” said Jeff Sharman, M.D., Disease Chair, Hematology Executive Committees, SCRI at Willamette Valley Cancer Institute and Research Center, and one of the principal investigators of the BRUIN CLL-321 trial, in the release. “When covalent BTK inhibitors are no longer an option due to disease progression or intolerance, pirtobrutinib enables physicians to extend the benefits of targeting the BTK pathway, offering continuity in the CLL or SLL treatment experience.”
