Lilly's Jaypirca cleared by FDA as first-line option for certain CLL/SLL patients

FDA indication

The U.S. FDA approved an additional indication for Jaypirca (pirtobrutinib) for adult patients with previously untreated chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) with no known 17p deletion, allowing use as a first-line treatment for appropriate patients.

Clinical evidence

The approval was based on the primary analysis of the Phase 3 BRUIN CLL-313 study, which randomized 282 treatment‑naïve patients without 17p deletion to pirtobrutinib or bendamustine plus rituximab (BR). At a median follow-up of 28 months, blinded IRC-assessed progression‑free survival (PFS) favored pirtobrutinib (HR=0.20; 95% CI 0.11–0.37), with median PFS not reached for pirtobrutinib versus 33.5 months for BR. IRC-assessed overall response rate (ORR) was 94% for pirtobrutinib (CR 13%; PR 81%) and 81% for BR (CR 21%; PR 60%).

Safety and dosing

Jaypirca is administered as a 200 mg once‑daily oral dose until disease progression or unacceptable toxicity. In BRUIN CLL-313, serious adverse reactions occurred in 28% of patients treated with pirtobrutinib; dose reductions occurred in 3.6% and permanent discontinuation in 4.3%. The prescribing information lists risks including infections, cytopenias, hemorrhage, cardiac arrhythmias, hepatotoxicity, second primary malignancies and embryo‑fetal toxicity; decreased neutrophil count and decreased hemoglobin were among the most common laboratory abnormalities.

Guidance and development

Jaypirca is the first‑and‑only FDA‑approved non‑covalent BTK inhibitor and is referenced in NCCN guidance (Category 2A for certain treatment‑naïve patients without del(17p) and Category 1 for relapsed/refractory patients previously treated with a covalent BTK inhibitor). Lilly is continuing multiple Phase 3 studies of pirtobrutinib across CLL/SLL treatment settings.