FDA grants traditional approval to pirtobrutinib for chronic lymphocytic leukemia and small lymphocytic lymphoma
Regulatory approval news: On Dec 3, 2025, the FDA granted traditional approval to pirtobrutinib (Jaypirca; Eli Lilly) for adults with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) previously treated with a covalent BTK inhibitor. Approval was supported by the randomized BRUIN-CLL-321 trial, which showed improved independent review committee–assessed progression-free survival versus investigator’s choice regimens. Updated overall survival results were reported with crossover permitted.
FDA action (regulatory approval)
On Dec 3, 2025, the FDA granted traditional approval to pirtobrutinib (Jaypirca; Eli Lilly and Company) for adults with relapsed or refractory CLL/SLL who have previously been treated with a covalent BTK inhibitor. In 2023, pirtobrutinib received accelerated approval for adults with CLL/SLL after ≥2 prior lines, including a BTK inhibitor and a BCL-2 inhibitor.
Key evidence
Efficacy was evaluated in BRUIN-CLL-321 (NCT04666038), a randomized, open-label, active-controlled trial (n=238) in previously treated CLL/SLL including a covalent BTK inhibitor; prior non-covalent BTK inhibitor therapy was not permitted. Patients were randomized 1:1 to pirtobrutinib or investigator’s choice of idelalisib + rituximab (IR) or bendamustine + rituximab (BR). Crossover to Jaypirca monotherapy after confirmed progression was allowed.
Primary endpoint: PFS by independent review committee (2018 iwCLL). Median PFS was 11.2 months (95% CI 9.5–11.4) with pirtobrutinib vs 8.7 months (95% CI 7.2–10.2) with IR/BR (HR 0.58, 95% CI 0.38–0.89; p=0.0105). With median follow-up 19.8 months, OS HR was 1.09 (95% CI 0.68–1.75).
Safety and dosing
Label warnings/precautions include infections, hemorrhage, cytopenias, cardiac arrhythmias, secondary primary malignancies, hepatotoxicity, and embryo-fetal toxicity. Recommended dose: 200 mg orally once daily until progression or unacceptable toxicity.