FDA

Jaypirca OK’d for relapsed/refractory CLL/SLL

December 5, 2025

On December 3, 2025, FDA granted traditional approval to Jaypirca (pirtobrutinib) for adults with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) who’ve previously been treated with a covalent BTK inhibitor. In 2023, the agency granted accelerated approval to pirtobrutinib for adults with CLL/SLL who’ve received at least two prior lines of therapy, including a BTK inhibitor and a BCL-2 inhibitor.

This FDA action expands the Jaypirca label to include patients earlier in their treatment course.

Efficacy

Efficacy was evaluated in the randomized, open-label, active-controlled BRUIN-CLL-321 trial (NCT04666038) involving 238 patients who were previously treated for CLL/SLL, including a covalent BTK inhibitor. Patients previously treated with a non-covalent BTK inhibitor were not permitted. Participants were randomized (1:1) to receive either pirtobrutinib or investigator’s choice of idelalisib plus a rituximab product (IR) or bendamustine plus a rituximab product (BR). Crossover to Jaypirca monotherapy was permitted for patients in the investigator’s choice arm after confirmed disease progression.

Primary efficacy outcome measure was progression-free survival (PFS), as assessed by an independent review committee using 2018 iwCLL criteria. Median PFS was 11.2 months (95% confidence interval [CI], 9.5-11.4) in the pirtobrutinib arm and 8.7 months (95% CI, 7.2-10.2) in the investigator’s choice of IR/BR arm (hazard ratio [HR], 0.58; 95% CI, 0.38-0.89; p-value 0.0105). Of the 119 patients in the investigator’s choice arm, 50 crossed over to receive Jaypirca therapy. At an updated analysis with a median follow-up time of 19.8 months, the HR for overall survival was 1.09 (95% CI, 0.68-1.75).

Safety

The prescribing information includes warnings and precautions for infections, hemorrhage, cytopenias, cardiac arrhythmias, secondary primary malignancies, hepatotoxicity, and embryo-fetal toxicity.

Recommended dose

The recommended pirtobrutinib dose is 200 mg orally once daily until disease progression or unacceptable toxicity.

Sources:

FDA grants traditional approval to pirtobrutinib for chronic lymphocytic leukemia and small lymphocytic leukemia. [News release]. 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-traditional-approval-pirtobrutinib-chronic-lymphocytic-leukemia-and-small-lymphocytic

Jaypirca (pirtobrutinib) [package insert]. Eli Lilly. https://pi.lilly.com/us/jaypirca-uspi.pdf Revised December 2025. Accessed December 4, 2025.

US FDA approves expanded indication for Lilly’s Jaypirca (pirtobrutinib), the first and only non-covalent (reversible) BTK inhibitor, for adults with relapsed or refractory CLL/SLL previously treated with a covalent BTK inhibitor. [News release]. 2025. https://investor.lilly.com/news-releases/news-release-details/us-fda-approves-expanded-indication-lillys-jaypirca