Jaypirca FDA Approval Expands Pirtobrutinib Use in CLL/SLL

Eli Lilly and Company announced on October 2, 2026, that the U.S. Food and Drug Administration (FDA) approved an additional indication for Jaypirca (pirtobrutinib) for adults with previously untreated chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) with no known 17p deletion. The approval expands Jaypirca’s use into the first-line treatment setting for this patient population.

The FDA decision was based on results from the Phase 3 BRUIN CLL-313 trial, which evaluated pirtobrutinib against bendamustine plus rituximab in previously untreated patients with CLL/SLL with no known 17p deletion.

BRUIN CLL-313 Trial

BRUIN CLL-313 (NCT05023980) was a Phase 3, global, randomized, open-label study that enrolled 282 patients with previously untreated CLL/SLL with no known 17p deletion. Patients were randomized 1:1 to receive either pirtobrutinib or bendamustine plus rituximab.

Patients assigned to the pirtobrutinib group received 200 mg orally once daily until disease progression or unacceptable toxicity. The comparator group received bendamustine plus rituximab for six cycles according to the study protocol.

The primary endpoint was progression-free survival (PFS), assessed by a blinded independent review committee (IRC). Secondary endpoints included overall response rate (ORR), duration of response, investigator-assessed PFS, overall survival, time to next treatment, safety and tolerability, and patient-reported outcomes.

Lilly reported that BRUIN CLL-313 is the first prospective, randomized Phase 3 study evaluating the efficacy and safety of a non-covalent BTK inhibitor in previously untreated CLL/SLL with no known 17p deletion.

Pirtobrutinib Significantly Improves Progression-Free Survival

At a median follow-up of 28 months, BRUIN CLL-313 met its primary endpoint. IRC-assessed PFS was significantly improved with pirtobrutinib compared with bendamustine plus rituximab, with a hazard ratio of 0.20 (95% CI, 0.11–0.37; p<0.0001).

Median PFS had not yet been reached in the pirtobrutinib group compared with 33.5 months in the bendamustine-plus-rituximab group.

The IRC-assessed overall response rate was 94% (95% CI, 89–98) with pirtobrutinib and 81% (95% CI, 73–87) with bendamustine plus rituximab. Complete responses occurred in 13% of patients receiving pirtobrutinib and 21% of those receiving bendamustine plus rituximab, while partial responses occurred in 81% and 60%, respectively.

Safety Findings

In BRUIN CLL-313, adverse reactions led to dose reductions in 3.6% of patients receiving Jaypirca, while permanent treatment discontinuation because of adverse reactions occurred in 4.3% of patients. Serious adverse reactions were reported in 28% of patients receiving pirtobrutinib. Pneumonia was the only serious adverse reaction reported in at least 3% of patients, occurring in 5%.

The median duration of treatment with pirtobrutinib was 32 months, and 92% of patients remained on treatment for more than 24 months. Atrial fibrillation or flutter occurred in 1.4% of patients.

Lilly stated that the overall safety profile, including the rate of atrial fibrillation or flutter, was consistent with previously reported trials of pirtobrutinib across treatment settings.

The Jaypirca labeling includes warnings and precautions for infections, hemorrhage, cytopenias, cardiac arrhythmias, second primary malignancies, hepatotoxicity including drug-induced liver injury, and embryo-fetal toxicity.

Jaypirca and BTK Inhibition

Pirtobrutinib is a highly selective, non-covalent BTK inhibitor that binds to both wild-type and C481-mutated BTK. Its non-covalent binding mechanism allows pirtobrutinib to inhibit BTK, including the C481-mutated form associated with resistance to covalent BTK inhibitors.

Jaypirca is an oral prescription medicine available as 50 mg and 100 mg tablets. The recommended dose is 200 mg once daily, with or without food, until disease progression or unacceptable toxicity.

With the FDA approval, Jaypirca is now indicated for adults with previously untreated CLL/SLL with no known 17p deletion, in addition to its previously approved use in adults with relapsed or refractory CLL/SLL who have previously received a covalent BTK inhibitor.

Reference

Lilly’s Jaypirca (pirtobrutinib), the first-and-only approved non-covalent BTK inhibitor, receives expanded indication from U.S. FDA for certain patients with previously untreated CLL/SLL, Eli Lilly and Company, October 2, 2026.

A Study of Pirtobrutinib (LOXO-305) Versus Bendamustine Plus Rituximab (BR) in Untreated Patients with Chronic Lymphocytic Leukemia (CLL)/​Small Lymphocytic Lymphoma (SLL) (BRUIN-CLL-313), ClinicalTrials.gov ID NCT05023980

U.S. Food and Drug Administration. FDA approves pirtobrutinib for previously untreated chronic lymphocytic leukemia or small lymphocytic lymphoma with no known 17p deletion. October 2, 2026