By Fineline Cube 
US pharmaceutical giant Eli Lilly & Co. (NYSE: LLY) announced on July 29, 2025, that its non-covalent, reversible BTK inhibitor, Jaypirca (pirtobrutinib), achieved its primary endpoint in the Phase III BRUIN CLL-314 head-to-head study for the treatment of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). This marks the first Phase III trial directly comparing a non-covalent BTK inhibitor with a covalent BTK inhibitor, Imbruvica (ibrutinib), in treatment-naïve patients.
Clinical Trial Design and Results
The BRUIN CLL-314 trial enrolled 650 patients with CLL/SLL, including those who were treatment-naïve or had previously been treated but not with a BTK inhibitor. Patients were randomized 1:1 to receive either pirtobrutinib (200mg once daily) or ibrutinib (420mg once daily). The primary endpoint was Overall Response Rate (ORR) as assessed by a Blinded Independent Review Committee (IRC). The study demonstrated that pirtobrutinib was non-inferior to ibrutinib in terms of ORR and showed a statistical advantage. A pronounced trend in progression-free survival (PFS) was observed among treatment-naïve patients (n=225), although PFS data are still immature. The results favored pirtobrutinib, and no adverse impact on overall survival (OS) was observed. The safety profile of pirtobrutinib was consistent with previous studies, with no new serious adverse reactions identified.
Significance and Future Steps
These results follow the success of the BRUIN CLL-321 study and, together with ongoing data from the BRUIN CLL-313 study, will support global regulatory submissions for pirtobrutinib. Jaypirca is currently approved in the U.S. for CLL/SLL patients who have previously received both a BTK inhibitor and a BCL-2 inhibitor. Full data from the BRUIN CLL-314 trial will be presented at a medical conference later in 2025.-Fineline Info & Tech