The Jaypirca Approval marks a new chapter for Eli Lilly and Company (NYSE: LLY), which announced on October 2, 2026, that the U.S. Food and Drug Administration (FDA) has cleared an additional indication for Jaypirca (pirtobrutinib), its non-covalent Bruton tyrosine kinase (BTK) inhibitor. The decision covers adult patients with previously untreated chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) who have no known 17p deletion, and it allows physicians to use the medicine as a first-line treatment for appropriate patients.
Lilly describes Jaypirca as the first-and-only FDA-approved non-covalent BTK inhibitor. It is an oral prescription tablet, supplied in 100 mg and 50 mg strengths and taken as a once-daily 200 mg dose, with or without food, until disease progression or unacceptable toxicity. Before this decision, the U.S. label centered on relapsed or refractory disease, so the newest step moves pirtobrutinib to the start of the treatment pathway.
Jennifer A. Woyach, M.D., who directs the Division of Hematology at The Ohio State University Comprehensive Cancer Center, said physicians can now consider the drug “not just later in a patient’s treatment journey.” She added that many people diagnosed with CLL or SLL today may receive only one or two lines of therapy, which makes the first choice especially important.
Jaypirca Approval Rests on BRUIN CLL-313 Phase 3 Evidence
The Jaypirca Approval is based on the primary analysis of BRUIN CLL-313, a global, randomized, open-label Phase 3 study registered as NCT05023980. The trial enrolled 282 patients with previously untreated CLL/SLL without 17p deletion and randomized them 1:1 to pirtobrutinib at 200 mg once daily or to bendamustine plus rituximab (BR) at labeled doses. Results were presented at the American Society of Hematology Annual Meeting in December 2025 and published in The Journal of Clinical Oncology.
Lilly states that BRUIN CLL-313 is the first prospective, randomized Phase 3 study to examine a non-covalent BTK inhibitor in this untreated population. At a median follow-up of 28 months, the primary endpoint of progression-free survival (PFS), assessed by an Independent Review Committee (IRC), was significantly improved with pirtobrutinib versus BR. The hazard ratio was 0.20 (95% CI, 0.11 to 0.37; p<0.0001), and median PFS was not yet reached for pirtobrutinib compared with 33.5 months for BR.
Response data supported the Jaypirca Approval as well. IRC-assessed overall response rate (ORR) was 94% with pirtobrutinib and 81% with BR. Complete responses were 13% in the pirtobrutinib arm and 21% in the BR arm, while partial responses were 81% and 60%, respectively. The release does not report overall survival results for the primary analysis, so that figure is listed as not disclosed below.
BRUIN CLL-313 Efficacy Data
| Measure | Pirtobrutinib (Jaypirca) | Bendamustine + Rituximab (BR) |
|---|---|---|
| Patients per arm | 141 | 141 |
| Median follow-up | 28 months | 28 months |
| IRC-assessed PFS hazard ratio | 0.20 (95% CI, 0.11-0.37); p<0.0001 | Reference |
| Median PFS | Not yet reached | 33.5 months |
| IRC-assessed ORR | 94% (95% CI, 89-98) | 81% (95% CI, 73-87) |
| Complete response (CR) | 13% | 21% |
| Partial response (PR) | 81% | 60% |
| Overall survival | Not disclosed | Not disclosed |
Safety Profile Behind the Jaypirca Approval and Its Label Warnings
In BRUIN CLL-313, adverse reactions (ARs) led to dose reductions in 3.6% of patients and permanent discontinuation of Jaypirca in 4.3%. Serious ARs occurred in 28% of pirtobrutinib-treated patients, and pneumonia (5%) was the only serious AR reported at a rate of 3% or higher. Lilly says the overall safety profile was consistent with earlier trials across treatment settings.
Cardiac safety draws close attention with BTK inhibitors, and the Jaypirca Approval data show a low rate of all-grade atrial fibrillation or flutter of 1.4%. Median treatment duration was 32 months, with 92% of patients on treatment for more than 24 months. Patients with significant cardiovascular disease, including uncontrolled or symptomatic arrhythmias, were excluded from the study, which clinicians should keep in mind when interpreting the figure.
The most frequent all-grade ARs of 20% or more were upper respiratory tract infection (27%), rash (22%), and COVID-19, including COVID-19 pneumonia (21%). Select laboratory abnormalities that worsened from baseline included decreased neutrophil count (48%), increased bilirubin (30%), increased ALT (27%), decreased hemoglobin (24%), and increased sodium (20%).
The Jaypirca Approval keeps the full set of label warnings in place. These cover infections, hemorrhage, cytopenias, cardiac arrhythmias, second primary malignancies, hepatotoxicity including drug-induced liver injury, and embryo-fetal toxicity. Across all clinical trials, Grade 3 or higher infections occurred in 23% of patients, and in patients with CLL/SLL, fatal infections occurred in 5%. Lilly also advises avoiding strong CYP3A inhibitors and strong or moderate CYP3A inducers where possible, and notes that patients aged 65 and older had higher rates of Grade 3 or higher and serious ARs in pooled data.
BRUIN CLL-313 Safety Data
| Measure | Reported Value |
|---|---|
| ARs leading to dose reduction | 3.6% |
| ARs leading to permanent discontinuation | 4.3% |
| Serious ARs | 28% |
| Serious AR at 3% or higher | Pneumonia (5%) |
| Atrial fibrillation or flutter (all grades) | 1.4% |
| Median treatment duration | 32 months |
| Patients on treatment for more than 24 months | 92% |
| Upper respiratory tract infection (all grades) | 27% |
| Rash (all grades) | 22% |
| COVID-19 including pneumonia (all grades) | 21% |
