Lilly's Jaypirca (pirtobrutinib), the first and only approved non-covalent (reversible) BTK inhibitor, met its primary endpoint in a head-to-head Phase 3 trial versus Imbruvica (ibrutinib) in CLL/SLL

Core Insights - Eli Lilly and Company announced positive topline results from the Phase 3 BRUIN CLL-314 clinical trial of Jaypirca (pirtobrutinib), demonstrating non-inferiority in overall response rate (ORR) compared to Imbruvica (ibrutinib) in patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) [1][2][3] Group 1: Clinical Trial Results - The BRUIN CLL-314 trial is the first head-to-head Phase 3 study against a covalent BTK inhibitor that includes treatment-naïve patients, with a total enrollment of 650 patients [1][4] - The primary endpoint of non-inferiority on ORR was met, with pirtobrutinib showing a nominal P-value for superiority of less than 0.05 [1][4] - Progression-free survival (PFS) data is still immature but is trending in favor of pirtobrutinib, with a formal analysis planned for the future [1][2] Group 2: Safety and Efficacy - The overall safety profile of pirtobrutinib in the trial was consistent with previous studies, and detailed results will be presented at a medical congress later in 2025 [2][3] - In the treatment-naïve subpopulation (n=225), a pronounced PFS effect size was observed in favor of pirtobrutinib [2] Group 3: Future Developments - The results from BRUIN CLL-314 build on previously reported positive outcomes from the BRUIN Phase 1/2 trial and the Phase 3 BRUIN CLL-321 trial, which focused on post-covalent BTK inhibitor populations [3] - The BRUIN CLL-313 Phase 3 study is expected to read out later in 2025, and combined results will support regulatory submissions globally [3]