Positive Phase 3 Results for Jaypirca
Eli Lilly’s Bruton tyrosine kinase (BTK) inhibitor Jaypirca has achieved the primary endpoint in a phase 3 clinical trial, moving closer to broader use among patients with blood cancer. In the BRUIN CLL-313 study, Jaypirca was tested in patients with treatment-naïve chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (CLL/SLL) without 17p deletions. Results showed that the therapy outperformed the chemoimmunotherapy combination of bendamustine plus rituximab.
Clinically Meaningful Improvement
According to Eli Lilly, Jaypirca demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS), described as “one of the most compelling effect sizes ever observed for a single agent BTK inhibitor in a front-line CLL study.” While overall survival (OS), a key secondary endpoint, was not yet mature, Lilly reported that results were trending strongly in favor of Jaypirca. The company stated it expects a full OS assessment by the end of this year.
Expanding Jaypirca’s Role
The BRUIN CLL-313 study is seen as a step toward expanding Jaypirca’s role as a first-line therapy. The U.S. Food and Drug Administration (FDA) granted accelerated approval in 2023 for Jaypirca as a treatment for CLL, SLL, and mantle cell lymphoma in patients who had received at least two prior lines of therapy, including one with another BTK inhibitor. Eli Lilly said data from BRUIN CLL-313 will be presented at an upcoming medical conference and combined with results from the BRUIN CLL-314 trial to support global regulatory submissions later this year. In BRUIN CLL-314, results released in July showed Jaypirca matched the performance of AbbVie and Johnson & Johnson’s Imbruvica, the first BTK inhibitor approved for blood cancer treatment.
A Unique Mechanism of Action
Commenting on the findings, Jacob Van Naarden, president of Eli Lilly Oncology, said, “The results from BRUIN CLL-313 are striking and provocative, across both PFS and OS endpoints, further demonstrating the potential of pirtobrutinib to be a meaningful treatment option for people with untreated CLL/SLL.”
Jaypirca distinguishes itself from other BTK inhibitors, including Imbruvica, AstraZeneca’s Calquence, and BeOne Medicines’ Brukinsa, as it is a non-covalent BTK inhibitor. This allows it to be used sequentially after other BTK therapies, as it binds differently to the protein. Eli Lilly highlighted this feature as giving Jaypirca an opportunity to treat patients whose disease progresses on covalent BTK inhibitors, which is a common occurrence in blood cancer treatment.
Market Performance and Future Outlook
Although recent results emphasize Jaypirca’s potential in first-line therapy, Van Naarden has previously noted that it was not considered the drug’s initial core value proposition. He stated at a healthcare conference that the company views the treatment as significant regardless of whether it becomes a first- or second-line option.
In the BRUIN CLL-313 study, 282 patients were randomly assigned to receive either Jaypirca or chemoimmunotherapy. Earlier this year, Jaypirca had also shown greater effectiveness than Imbruvica in a direct comparison trial.
Jaypirca generated $337 million in sales in 2024, up from $215 million in the first half of 2025. For comparison, sales of Calquence and Brukinsa reached $3.1 billion and $2.6 billion, respectively, in 2024, while Imbruvica’s revenue declined from its $9.8 billion peak in 2021 to $6.4 billion last year.
Eli Lilly stated that results from its ongoing studies will be used to pursue label expansions and support regulatory submissions in earlier lines of therapy later this year.
Conclusion
Looking ahead, the success of Jaypirca in BRUIN CLL-313 sets up a number of potential next steps for both clinicians and patients. Oncology treatment algorithms may begin to incorporate non-covalent BTK inhibition earlier in the course of disease, particularly in patients who are BTK-naïve or have risk factors for covalent inhibitor resistance. Real-world data post-approval will be critical to understanding how treatment sequencing, duration of response and safety translate outside of the clinical-trial setting.
In summary, Eli Lilly’s Jaypirca is poised for a potential step change in CLL/SLL treatment — moving from its current indication in later-lines toward first-line use. As full OS data emerges and regulatory reviews progress, the oncology community will watch closely how this novel non-covalent BTK inhibitor integrates into standard practice.
