Eli Lilly’s Jaypirca (pirtobrutinib) has succeeded in its fourth Phase III trial in chronic lymphocytic leukaemia (CLL).
The Phase III BRUIN CLL-322 trial (NCT04965493) met its primary endpoint, demonstrating that the addition of Jaypirca to venetoclax plus rituximab led to a statistically significant and clinically meaningful improvement in progression-free survival (PFS) in patients with CLL or small lymphocytic lymphoma (SLL).
Go deeper with GlobalData
Discover B2B Marketing That Performs
Combine business intelligence and editorial excellence to reach engaged professionals across 36 leading media platforms.
Results were consistent across clinically relevant subgroups and regardless of whether patients were previously treated with a covalent BTK inhibitor.
Overall survival (OS), a key secondary endpoint, was not yet mature at this analysis, but Lilly said it is trending in favour of the Jaypirca combination regimen.
The overall safety profile of this regimen was consistent with the known safety profile of each medicine. Rates of adverse events were similar across the study arms, with low rates of treatment regimen discontinuations also similar between arms.
The non-covalent (reversible) Bruton tyrosine kinase (BTK) inhibitor was investigated in combination with venetoclax and rituximab versus venetoclax and rituximab alone. Patients received treatment for up to two years, after which patients do not receive any CLL therapy until their disease progressed.
Detailed results will be presented at a medical congress and submitted to a peer-reviewed journal. Lilly intends to submit these results to regulators later this year for a label expansion.
Jacob Van Naarden, executive vice president and president of Lilly Oncology, said that the study outperformed expectations.
Naarden said: “Modern CLL treatment regimens provide such durable disease control that the vast majority of patients see their entire disease course managed by only one or two lines of therapy. For doctors and patients who prefer a time-limited approach, these BRUIN CLL-322 data demonstrate that the addition of Jaypirca could further extend the duration of benefit in second-line CLL.”
This readout follows successful data from three other Phase III trials, BRUIN CLL-321 (NCT04666038), BRUIN CLL-314 (NCT05254743) and BRUIN CLL-313 (NCT05023980), all of which showed Jaypirca’s benefit in CLL. BRUIN CLL-322, however, is the first Phase III readout in CLL to utilise and outperform a venetoclax-containing control arm.
The drug first gained accelerated US Food and Drug Administration (FDA) approval in 2023 for use in adults with CLL/SLL who have received at least two prior lines of therapy, including a BTK inhibitor and a BCL-2 inhibitor. In December 2025, the drug gained traditional approval for use in patients with CLL and SLL who have previously been treated with a covalent BTK inhibitor.
GlobalData’s patient-based forecast predicts global sales of Jaypirca to reach $1.34bn in CLL alone in 2032. The overall forecast for the CLL market across the seven major pharmaceutical markets (7MM; US, France, Germany, Italy, Spain, UK, and Japan) in 2032 is $10.8bn, up from $9.9bn in 2022.
Key drivers, in addition to Jaypirca, are expected to be BeOne Medicines’ Brukinsa, AstraZeneca’s Calquence, and Bristol Myers Squibb’s CAR-T Breyanzi.
GlobalData is the parent company of Clinical Trials Arena.
