Pirtobrutinib met the primary endpoint of response rate non-inferiority, favoring pirtobrutinib with a nominal P-value for superiority < 0.05

Progression-free survival data was immature, but trending in favor of pirtobrutinib

BRUIN CLL-314 is the first-ever head-to-head Phase 3 study versus a covalent BTK inhibitor to include treatment-naïve patients

Abu Dhabi, United Arab Emirates. August12, 2025:Eli Lilly and Company (NYSE: LLY) today announced positive topline results from the Phase 3 BRUIN CLL-314 clinical trial of Jaypirca (pirtobrutinib), a non-covalent (reversible) Bruton’s tyrosine kinase (BTK) inhibitor, versus Imbruvica (ibrutinib), a covalent BTK inhibitor, in patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL). This study enrolled patients with treatment-naïve CLL/SLL and those who had been previously treated but were BTK inhibitor-naïve. The study met its primary endpoint of non-inferiority on overall response rate (ORR) as assessed by an independent review committee (IRC) in both the pre-treated and intent-to-treat populations. ORR favored pirtobrutinib with a nominal P-value for superiority¹ (p <0.05). Progression free survival (PFS), a key secondary endpoint, was not yet mature at this analysis, but was trending in favor of pirtobrutinib. A formal PFS analysis testing for superiority is planned ata future analysis. No detriment was observed for overall survival (OS).

BRUIN CLL-314 is the first ever head-to-head trial versus ibrutinib in CLL to include treatment-naïve patients. This important subpopulation (n=225) had the longest follow-up and a particularly pronounced PFS effect size in favor of pirtobrutinib.

The overall safety profile of pirtobrutinib in BRUIN CLL-314 was similar to previously reported trials. Detailed results will be presented at a medical congress later in 2025.