FDA Approves Jaypirca as First-Line Treatment for CLL and SLL

The Food and Drug Administration (FDA) has approved Jaypirca (pirtobrutinib) as a first-line treatment for adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who have no known 17p deletion.

The approval is based on findings from the phase 3 BRUIN CLL-313 trial, in which Jaypirca delayed disease progression compared with bendamustine plus Rituxan (rituximab), a chemoimmunotherapy combination.

"This approval is grounded in data from BRUIN CLL-313, which showed a significant delay in disease progression for [Jaypirca] compared to chemoimmunotherapy, along with safety and tolerability consistent with its established profile," said Dr. Jennifer A. Woyach, director of the Division of Hematology at The Ohio State University, in a news release issued by Eli Lilly and Company.

CLL and SLL are slow-growing forms of the same cancer that start in white blood cells called lymphocytes. In CLL, cancer cells are found mainly in the blood, while in SLL they are found mainly in the lymph nodes.

A 17p deletion occurs when part of chromosome 17 is missing. It is found in approximately 5% to 8% of patients with CLL or SLL at diagnosis and is associated with a higher risk of disease progression.

Jaypirca is a pill that blocks Bruton tyrosine kinase (BTK), a protein involved in the growth and survival of certain cancerous B cells. Imbruvica (ibrutinib), Calquence (acalabrutinib) and Brukinsa (zanubrutinib) are covalent BTK inhibitors, while Jaypirca is a noncovalent BTK inhibitor, meaning it binds to BTK differently. Trials have not directly compared whether these different binding mechanisms affect outcomes for patients.

What did the phase 3 BRUIN CLL-313 trial show in untreated CLL and SLL?

After a median follow-up of 28 months, Jaypirca significantly reduced the risk of disease progression or death compared with bendamustine plus Rituxan.

The hazard ratio for disease progression or death was 0.20, meaning patients who received Jaypirca had an approximately 80% lower risk during the study period than those who received bendamustine plus Rituxan.

Median progression-free survival (PFS), or the length of time patients lived without their cancer growing or spreading, had not yet been reached with Jaypirca. This means more than half of patients receiving Jaypirca had not experienced disease progression by the time of the analysis. Median PFS was 33.5 months with bendamustine plus Rituxan.

The overall response rate, or the percentage of patients whose cancer shrank or disappeared, was 94% with Jaypirca versus 81% with bendamustine plus Rituxan.

Complete responses, meaning no remaining signs of cancer were detected, occurred in 13% of patients who received Jaypirca and 21% who received bendamustine plus Rituxan. Partial responses occurred in 81% and 60% of patients, respectively.

The approval allows Jaypirca to be used earlier in the treatment course, Woyach noted.

"Doctors can now consider [Jaypirca] for appropriate patients when initial therapy is needed, not just later in a patient's treatment journey," she said. "Given the efficacy and tolerability of modern targeted therapies, coupled with factors like age or [other health conditions], many people diagnosed with CLL or SLL today may only receive one or two lines of therapy, making initial treatment choices critically important."

How was the BRUIN CLL-313 trial designed?

The global, open-label phase 3 trial included 282 adults with previously untreated CLL or SLL without a 17p deletion.

Patients were randomly assigned to receive either Jaypirca or bendamustine plus Rituxan, with 141 patients in each group. Jaypirca was taken by mouth at a dose of 200 milligrams once daily until the cancer progressed or side effects became too difficult to tolerate. Bendamustine plus Rituxan was given at its approved doses.

Because the trial was open label, both patients and their doctors knew which treatment was being given.

The trial's main goal was progression-free survival as assessed by an independent review committee. Researchers also evaluated response rates, overall survival, safety and other outcomes.

Patients with significant heart disease, including uncontrolled or symptomatic irregular heart rhythms, were not eligible to participate.

What side effects occurred with Jaypirca?

Patients received Jaypirca for a median of 32 months, and 92% remained on treatment for more than two years.

Side effects led to a dose reduction in 3.6% of patients and caused 4.3% to permanently stop Jaypirca. Serious side effects occurred in 28% of patients, with pneumonia reported in 5%.

The most common side effects of any severity were upper respiratory tract infection, occurring in 27% of patients; rash, in 22%; and COVID-19, including COVID-19 pneumonia, in 21%. Atrial fibrillation or flutter, two types of irregular heartbeat, occurred in 1.4% of patients.

Blood test abnormalities that worsened from the start of treatment included decreased neutrophils, a type of white blood cell that helps fight infection, in 48% of patients; increased bilirubin in 30%; increased ALT in 27%; decreased hemoglobin in 24%; and increased sodium in 20%. Bilirubin and ALT are measures that can help doctors assess liver health.

The Jaypirca label includes warnings for infections, bleeding, low blood cell counts, irregular heart rhythms, new cancers, liver damage and harm to an unborn baby.

The BRUIN CLL-313 findings were presented at the American Society of Hematology Annual Meeting and Exposition in December 2025 and published in the Journal of Clinical Oncology. Jaypirca is also being studied in several other phase 3 CLL and SLL trials, including BRUIN CLL-314, which compared Jaypirca with Imbruvica.

References

1. News release. "Lilly's Jaypirca (pirtobrutinib), the first-and-only approved non-covalent BTK inhibitor, receives expanded indication from U.S. FDA for certain patients with previously untreated CLL/SLL." Eli Lilly and Company. Posted October 2, 2026.
2. Jurczak W, et al. "BRUIN CLL-313: Randomized Phase III Trial of Pirtobrutinib Versus Bendamustine Plus Rituximab in Untreated Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma." Journal of Clinical Oncology. 2026;44(6):466-475.

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