FDA expands Jaypirca (pirtobrutinib) to previously untreated CLL/SLL – Eli Lilly
Eli Lilly and Company announced that the FDA has approved an additional indication for Jaypirca (pirtobrutinib, 100 mg & 50 mg tablets), a non-covalent Bruton tyrosine kinase (BTK) inhibitor, for the treatment of adult patients with previously untreated chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) with no known 17p deletion.
This approval allows for the use of Jaypirca as a first-line treatment for appropriate patients. Jaypirca, the first-and-only FDA-approved non-covalent BTK inhibitor, is a highly selective kinase inhibitor that utilizes a novel non-covalent binding mechanism to target the BTK pathway in patients with CLL/SLL.
“This approval is grounded in data from BRUIN CLL-313, which showed a significant delay in disease progression for pirtobrutinib compared to chemoimmunotherapy, along with safety and tolerability consistent with its established profile,” said Jennifer A. Woyach, M.D., professor, hematologist-oncologist, and Director of the Division of Hematology at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute. “Doctors can now consider pirtobrutinib for appropriate patients when initial therapy is needed, not just later in a patient’s treatment journey. Given the efficacy and tolerability of modern targeted therapies – coupled with factors like age or comorbidity – many people diagnosed with CLL or SLL today may only receive one or two lines of therapy, making initial treatment choices critically important.”
The FDA approval is based on results from the primary analysis of the BRUIN CLL-313 clinical trial, which were presented at the American Society of Hematology Annual Meeting and Exposition in December 2025 and published in The Journal of Clinical Oncology. BRUIN CLL-313 is the first prospective, randomized Phase 3 study to examine the efficacy and safety of a non-covalent BTK inhibitor in patients with previously untreated CLL/SLL without 17p deletion.
In BRUIN CLL-313, at a median follow-up of 28 months, the primary endpoint of Independent Review Committee (IRC)-assessed progression-free survival (PFS) was significantly improved with pirtobrutinib (n=141) compared to bendamustine plus rituximab (BR) (n=141) (HR=0.20 [95% CI, 0.11–0.37]; p<0.0001), and the median PFS was not yet reached for pirtobrutinib compared to 33.5 months for BR. IRC-assessed overall response rate (ORR) was 94% (95% CI, 89–98) in the pirtobrutinib arm (complete response [CR]=13%; partial response [PR]=81%) and 81% (95% CI, 73–87) in the BR arm (CR=21%; PR=60%). In the BRUIN CLL-313 trial, adverse reactions (ARs) led to dose reductions in 3.6% and permanent discontinuation of Jaypirca in 4.3% of patients. Serious ARs occurred in 28% of patients who received Jaypirca. Serious ARs occurring in ≥3% of patients included pneumonia (5%). The overall safety profile, including rates of atrial fibrillation or flutter, for patients treated with pirtobrutinib in the BRUIN CLL-313 trial was consistent with previously reported trials across treatment settings.
“This additional approval for Jaypirca, based on BRUIN CLL-313, marks a significant step forward, expanding its potential to reach more patients who may benefit – this time as an initial treatment for certain previously untreated patients with CLL or SLL,” said Jacob Van Naarden, executive vice president and president of Lilly Oncology. “This milestone underscores Jaypirca’s versatility in the CLL continuum of care, from the first-line setting for appropriate patients to its valuable role in the relapsed or refractory post-covalent BTK inhibitor setting, reinforcing Jaypirca’s broad applicability as a meaningful treatment option for people with CLL or SLL.”
Jaypirca is the first-and-only non-covalent BTK inhibitor recommended by the National Comprehensive Cancer Network (NCCN). Jaypirca is Category 2A recommended for treatment-naïve adult patients with CLL/SLL without del(17p), recommended for older patients with cardiac comorbidities who may only need one lifetime treatment for CLL/SLL. Jaypirca is a Category 1 preferred option for adult patients with relapsed or refractory CLL/SLL who have previously been treated with a covalent BTK inhibitor.
The labeling for Jaypirca contains warnings and precautions for infections, hemorrhage, cytopenias, cardiac arrhythmias, second primary malignancies, hepatotoxicity including drug-induced liver injury and embryo-fetal toxicity.
Lilly is studying Jaypirca in CLL/SLL in multiple Phase 3 studies. Details on the trials can be found by visiting clinicaltrials.gov.
About BRUIN CLL-313
BRUIN CLL-313 (NCT05023980) is a Phase 3, global, randomized, open-label study of Jaypirca (pirtobrutinib) versus chemoimmunotherapy (BR) in people with CLL/SLL without 17p deletion who have not been previously treated. The trial enrolled 282 patients who were randomized 1:1 to receive pirtobrutinib (200 mg orally, once daily until disease progression or unacceptable toxicity) or BR per labeled doses. BR is a chemoimmunotherapy regimen used in the treatment of CLL. The primary endpoint is PFS as assessed by blinded IRC. Secondary endpoints include investigator and IRC-assessed ORR and duration of response (DoR), investigator-assessed PFS, overall survival (OS), time to next treatment (TTNT), safety and tolerability and patient-reported outcomes (PRO).
Citation: Jurczak W, Kwiatek M, Czyz J, et al. BRUIN CLL-313: Randomized Phase III Trial of Pirtobrutinib Versus Bendamustine Plus Rituximab in Untreated Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma. J Clin Oncol. 2026;44(6):466-475. doi:10.1200/JCO-25-02380
