The US Food and Drug Administration (FDA) has 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.

Efficacy was evaluated in BRUIN CLL-313 (NCT05023980), a randomised, open-label, active-controlled trial in 282 patients with previously untreated CLL/SLL without deletion of chromosome 17p. Patients were randomised 1:1 to receive pirtobrutinib (n=141) until disease progression or bendamustine plus a rituximab product (n=141) for 6 cycles.

The main efficacy outcome measure was Progression-Free Survival (PFS) as assessed by an Independent Review Committee (IRC). With an estimated median follow-up for PFS of 28 months, the median PFS was Not Estimable (NE) (95 percent CI: NE, NE) in the pirtobrutinib arm and 33.5 months (95 percent CI: 32.7, NE) in the bendamustine and rituximab arm (Hazard ratio 0.20 [95 percent 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: 3 deaths (2.1 percent) in the pirtobrutinib arm and 10 deaths (7.1 percent) in the control arm.

The most common (≥ 20 percent) non-laboratory adverse reactions occurring in patients receiving pirtobrutinib, were upper Respiratory Tract Infections (RTIs) (27 percent), rash (22 percent) and COVID-19 (21 percent). The most common (>10 percent) Grade 3 or 4 laboratory abnormality was neutrophil count decreased.

Serious adverse reactions occurred in 28 percent 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.

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 (ODD).