Eli Lilly's Jaypirca Achieves Landmark 80% Risk Reduction in Frontline CLL/SLL Treatment Study

Eli Lilly has unveiled compelling Phase 3 trial results for Jaypirca (pirtobrutinib), showcasing an impressive 80% reduction in disease progression or death risk compared to conventional chemotherapy in previously untreated chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) patients without 17p deletions.

Record-Breaking Efficacy Data

The BRUIN CLL-313 trial represents a watershed moment for non-covalent Bruton tyrosine kinase (BTK) inhibitors. At a median follow-up spanning 28.1 months, pirtobrutinib significantly outperformed the bendamustine plus rituximab (BR) combination across all measured endpoints. The progression-free survival (PFS) improvement stands out as one of the strongest single-agent BTK inhibitor performances ever documented in frontline CLL/SLL trials.

This is the first prospective, randomized Phase 3 investigation to exclusively evaluate a non-covalent BTK inhibitor against standard therapy in treatment-naïve CLL/SLL patients, making the findings particularly noteworthy for the field.

Trial Design and Patient Population

The study enrolled 282 treatment-naive patients with CLL/SLL lacking del(17p) mutations. Participants were randomly assigned 1:1 to receive continuous pirtobrutinib monotherapy or BR chemotherapy. The protocol permitted crossover to pirtobrutinib following independent review committee-confirmed disease progression, a provision that over half of the BR arm ultimately utilized.

Survival Trends and Future Outlook

While overall survival (OS) data remains immature at the July 11, 2025 cutoff, a favorable trend toward pirtobrutinib emerged despite the substantial crossover rate. Final OS superiority analysis is scheduled for future reporting.

Eli Lilly has begun regulatory submissions incorporating data from both BRUIN CLL-313 and BRUIN CLL-314 trials, with expansion of Jaypirca’s therapeutic indication into earlier treatment lines as a strategic objective. The company continues advancing multiple Phase 3 studies examining Jaypirca’s potential across various CLL/SLL patient populations.