Promising Results: Jaypirca Outperforms Imbruvica in Landmark Phase 3 CLL/SLL Trial

Jaypirca (pirtobrutinib), Eli Lilly’s first-in-class non-covalent BTK inhibitor, demonstrated superior overall response rates (p<0.05) compared to Imbruvica (ibrutinib) in the Phase 3 BRUIN CLL-314 trial for chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL), with early trends in progression-free survival and a consistent safety profile reinforcing its potential as a new standard of care.

BRUIN CLL-314 is distinguished as the first-ever head-to-head Phase 3 trial comparing pirtobrutinib directly with ibrutinib in CLL patients, especially noteworthy for including treatment-naïve individuals.

The study, which included both treatment-naïve patients and those previously treated but naïve to BTK inhibitors, successfully met its primary endpoint of non-inferiority regarding overall response rate (ORR), as determined by an independent review committee. Notably, the ORR outcome favored pirtobrutinib, achieving a nominal P-value for superiority (p<0.05).

"These data mark the second positive Phase 3 study in the program, as we continue to build evidence supporting the potential role of pirtobrutinib in treating people with CLL/SLL and hopefully enabling future regulatory approvals that allow physicians to use the medicine in various disease settings, whether treatment-naïve or BTK inhibitor-pretreated," said Jacob Van Naarden, Executive Vice President and President of Lilly Oncology.

While progression-free survival (PFS), a crucial secondary endpoint, was still immature at the time of analysis, preliminary data showed a favorable trend towards pirtobrutinib. This finding was particularly pronounced among the subgroup of treatment-naïve patients, who represented a significant portion of the trial (n=225) and had the longest follow-up period.

No adverse impact was observed on overall survival (OS), affirming pirtobrutinib’s safety profile consistent with previous clinical studies. Detailed safety and efficacy results are scheduled for presentation at an upcoming medical congress later this year.

These latest findings build upon previously reported successes, including the Phase 1/2 BRUIN trial and Phase 3 BRUIN CLL-321, marking a substantial expansion in clinical evidence supporting pirtobrutinib's efficacy and safety. Further pivotal results from the BRUIN CLL-313 trial, evaluating pirtobrutinib versus chemoimmunotherapy in treatment-naïve patients, are anticipated later this year and are expected to form the basis for global regulatory submissions.

Jaypirca (pirtobrutinib) represents an innovative treatment approach as a highly selective, non-covalent inhibitor of BTK, a critical molecular target involved in various B-cell malignancies. With FDA approval already secured in the U.S., Lilly aims to broaden the therapeutic applications of pirtobrutinib, potentially reshaping the treatment landscape for patients with CLL and SLL.