FDA approves pirtobrutinib for previously untreated chronic lymphocytic leukemia or small lymphocytic lymphoma

On October 2, 2026, the Food and Drug Administration approved pirtobrutinib (Jaypirca, Eli Lilly and Company) for adult patients with previously untreated chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) with no known 17p deletion.

Full prescribing information for Jaypirca will be posted on Drugs@FDA.

Efficacy and Safety

Efficacy was evaluated in BRUIN CLL-313 (NCT05023980), a randomized, open-label, active-controlled trial in 282 patients with previously untreated CLL/SLL without deletion of chromosome 17p. Patients were randomized 1:1 to receive pirtobrutinib (n=141) until disease progression or bendamustine plus a rituximab product (n=141) for six cycles.

The main efficacy outcome measure was progression-free survival (PFS) as assessed by an independent review committee. With an estimated median follow-up for PFS of 28 months, the median PFS was not estimable (NE) (95% CI: NE, NE) in the pirtobrutinib arm and 33.5 months (95% CI: 32.7, NE) in the bendamustine and rituximab arm (Hazard ratio 0.20 [95% CI: 0.11, 0.37]; p-value <0.0001). At the time of the primary PFS analysis, overall survival (OS) data was immature. The median OS was not reached in either arm with a total of 13 deaths: three deaths (2.1%) in the pirtobrutinib arm and 10 deaths (7.1%) in the control arm.

The most common (≥ 20%) non-laboratory adverse reactions occurring in patients receiving pirtobrutinib, were upper respiratory tract infections (27%), rash (22%) and COVID-19 (21%). The most common (>10%) Grade 3 or 4 laboratory abnormality was neutrophil count decreased. Serious adverse reactions occurred in 28% of patients taking pirtobrutinib.

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

Recommended Dosage

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

This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.

Pirtobrutinib received orphan drug designation.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.

For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.