-
Approval is based on results from the BRUIN CLL-321 trial, the only randomized Phase 3 study in CLL/SLL in which all patients were previously treated with a covalent BTK inhibitor
-
This expanded indication represents a substantial increase in the number of CLL/SLL patients who may benefit from Jaypirca and aligns with the patient population endorsed by the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®)
INDIANAPOLIS, Dec. 3, 2025 /PRNewswire/ -- Eli Lilly and Company (NYSE: LLY) today announced that the U.S. Food and Drug Administration (FDA) has granted approval to Jaypirca (pirtobrutinib, 100 mg & 50 mg tablets) for the treatment of adults with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) who have previously been treated with a covalent Bruton tyrosine kinase (BTK) inhibitor. This FDA action expands the Jaypirca label to include patients earlier in their treatment course and also converts the December 2023 accelerated approval for later-line CLL/SLL to a traditional approval.1
"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. "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."
Jaypirca, the first and only FDA-approved non-covalent (reversible) BTK inhibitor, is a highly selective kinase inhibitor that utilizes a novel non-covalent binding mechanism to extend the benefit of targeting the BTK pathway in patients with relapsed or refractory CLL/SLL previously treated with a covalent BTK inhibitor (ibrutinib, acalabrutinib, or zanubrutinib).1,2
"This label expansion allows physicians to use Jaypirca 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 and president of Lilly Oncology. "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."
"For CLL or SLL patients who progress following treatment with an irreversible or covalently binding BTK inhibitor, having additional therapeutic options is critical," said Brian Koffman, M.D., co-founder and chief medical officer emeritus at CLL Society. "With this approval, physicians and patients can stay in the same broad class of medicines with a treatment that offers meaningful impact on patient outcomes, saving the potential to use medicines with different targets for later therapy."
Lilly is studying Jaypirca in CLL/SLL in multiple Phase 3 studies. Details on the trials can be found by visiting clinicaltrials.gov.
See Important Safety Information below and full Prescribing Information for additional information.
About BRUIN CLL-321
BRUIN CLL-321 is a Phase 3, randomized, open-label study of Jaypirca versus investigator's choice of idelalisib plus rituximab (IdelaR) or bendamustine plus rituximab (BR) in covalent Bruton tyrosine kinase (BTK) inhibitor pre-treated patients with relapsed and refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). The trial enrolled 238 patients, who were randomized 1:1 to receive Jaypirca (200 mg orally, once daily) or investigator's choice of either IdelaR or BR per labeled doses. This trial's primary endpoint is progression-free survival (PFS) per 2018 International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria, as assessed by blinded independent review committee (IRC). Secondary endpoints include PFS, as assessed by investigator; overall response rate (ORR) and duration of response (DoR); event-free survival; overall survival (OS) and time to next treatment (TTNT); safety and tolerability; and patient-reported outcomes (PRO).
About Jaypirca (pirtobrutinib)
Jaypirca (pirtobrutinib, formerly known as LOXO-305) (pronounced jay-pihr-kaa) is a highly selective (300 times more selective for BTK versus 98% of other kinases tested in preclinical studies), non-covalent (reversible) inhibitor of the enzyme BTK.2 BTK is a validated molecular target found across numerous B-cell leukemias and lymphomas including mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL).3,4 Jaypirca is a U.S. FDA-approved oral prescription medicine, 100 mg or 50 mg tablets taken as a once-daily 200 mg dose with or without food until disease progression or unacceptable toxicity.
About Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are forms of slow-growing non-Hodgkin lymphoma that develop from white blood cells known as lymphocytes.5 CLL is one of the most common types of leukemia in adults.5 In the U.S., CLL accounts for about one-quarter of the new cases of leukemia and there will be approximately 23,690 new cases of CLL diagnosed this year.5,6 SLL is identical to CLL from a pathologic and immunophenotypic standpoint, with the main difference between them being the location of the cancer cells.5 In CLL, the cancer cells are present in the blood, and in SLL, the cancer cells are found in the lymph nodes.5
About Lilly
Lilly is a medicine company turning science into healing to make life better for people around the world. We've been pioneering life-changing discoveries for nearly 150 years, and today our medicines help tens of millions of people across the globe. Harnessing the power of biotechnology, chemistry and genetic medicine, our scientists are urgently advancing new discoveries to solve some of the world's most significant health challenges: redefining diabetes care; treating obesity and curtailing its most devastating long-term effects; advancing the fight against Alzheimer's disease; providing solutions to some of the most debilitating immune system disorders; and transforming the most difficult-to-treat cancers into manageable diseases. With each step toward a healthier world, we're motivated by one thing: making life better for millions more people. That includes delivering innovative clinical trials that reflect the diversity of our world and working to ensure our medicines are accessible and affordable.
Endnotes & References
-
Jaypirca. Prescribing Information. Lilly USA, LLC.
-
Mato AR, Shah NN, Jurczak W, et al. Pirtobrutinib in relapsed or refractory B-cell malignancies (BRUIN): a phase 1/2 study. Lancet. 2021;397(10277):892-901. doi:10.1016/S0140-6736(21)00224-5
-
Hanel W, Epperla N. Emerging therapies in mantle cell lymphoma. J Hematol Oncol. 2020;13(1):79. Published 2020 Jun 17. doi:10.1186/s13045-020-00914-1
-
Gu D, Tang H, Wu J, Li J, Miao Y. Targeting Bruton tyrosine kinase using non-covalent inhibitors in B cell malignancies. J Hematol Oncol. 2021;14(1):40. Published 2021 Mar 6. doi:10.1186/s13045-021-01049-7
-
Mukkamalla SKR, Taneja A, Malipeddi D, et al. Chronic Lymphocytic Leukemia. [Updated Feb 18, 2023]. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan. Available from: https://www.ncbi.nlm.nih.gov/books/NBK470433/
-
NCI SEER Program [NIH]. Cancer Stat Facts: Leukemia—Chronic Lymphocytic Leukemia (CLL). Accessed on September 3, 2025. https://seer.cancer.gov/statfacts/html/clyl.html