FDA clears Jaypirca as first line treatment for certain previously untreated CLL and SLL patients

The US Food and Drug Administration has approved a new indication for Eli Lilly’s Jaypirca (pirtobrutinib), widening its use to adults with previously untreated chronic lymphocytic leukaemia or small lymphocytic lymphoma who have no known 17p deletion. Jaypirca is a non covalent Bruton tyrosine kinase inhibitor, and the decision means eligible patients can now receive it as their first treatment. It remains the only approved drug of its type.

The approval is built on the primary analysis of the BRUIN CLL-313 trial, which was presented at the American Society of Hematology Annual Meeting and Exposition in December 2025 and published in The Journal of Clinical Oncology. The study is the first prospective, randomised Phase 3 trial to test a non covalent BTK inhibitor in previously untreated patients with CLL or SLL without 17p deletion.

After a median follow up of 28 months, pirtobrutinib cut the risk of progression or death by 80 per cent compared with bendamustine plus rituximab (HR=0.20; 95% CI, 0.11 to 0.37; p<0.0001), based on assessment by an independent review committee. Each arm enrolled 141 patients. Median progression free survival had not been reached with pirtobrutinib, against 33.5 months with bendamustine plus rituximab. The overall response rate was 94 per cent with pirtobrutinib (13 per cent complete responses and 81 per cent partial responses), compared with 81 per cent in the chemoimmunotherapy arm (21 per cent complete and 60 per cent partial).

On safety, side effects led to dose reductions in 3.6 per cent of patients taking Jaypirca and permanent discontinuation in 4.3 per cent. Serious adverse reactions occurred in 28 per cent of patients, with pneumonia the only one reaching at least 3 per cent (5 per cent). Overall safety, including rates of atrial fibrillation or flutter, matched what earlier trials had shown across other treatment settings. The label carries warnings and precautions covering infections, haemorrhage, cytopenias, cardiac arrhythmias, second primary malignancies, hepatotoxicity including drug induced liver injury, and embryo foetal toxicity.

Jennifer A. Woyach, M.D., professor, haematologist oncologist and director of the Division of Hematology at The Ohio State University Comprehensive Cancer Center, said the trial showed a significant delay in progression with pirtobrutinib compared with chemoimmunotherapy, alongside tolerability consistent with the drug’s known profile. She said doctors can now consider pirtobrutinib when a patient first needs treatment rather than only later on. Because modern targeted therapies work well and many patients are older or have other health conditions, she noted, many people diagnosed with CLL or SLL today may receive only one or two lines of treatment, which makes the first choice especially important.

Jacob Van Naarden, executive vice president and president of Lilly Oncology, called the approval a significant step that extends Jaypirca to more patients, this time as initial therapy for some previously untreated people with CLL or SLL. He said it shows the drug’s versatility across the course of the disease, from first line use in suitable patients to its role after covalent BTK inhibitors have stopped working in relapsed or refractory disease.

Jaypirca is also the only non covalent BTK inhibitor recommended by the National Comprehensive Cancer Network. Its guidelines give it a Category 2A recommendation for adults with untreated CLL or SLL without del(17p), including older patients with heart conditions who may need only one lifetime treatment. For adults with relapsed or refractory disease who have already received a covalent BTK inhibitor, it is a Category 1 preferred option.

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Related Topics and Keywords

FDA, jaypirca, SLL patients, untreated CLL