Two years after Jayprica’s initial approval, Eli Lilly and Company announced FDA’s approval of an expanded indication for Jayprica (Pirtobrutinin), a non-covalent BTK inhibitor.

Jaypirca was approved for the treatment of adults with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) who were previously treated with a covalent Bruton tyrosine kinase (BTK) inhibitor.

The approval expands Jaypirca’s label to include patients earlier in their treatment course and converts its accelerated approval for later-line CLL/SLL from December 2023 to a traditional approval.¹

"This label expansion allows physicians to use Jaypirca directly after a covalent BTK inhibitor, the setting where we have always believed it has its most unique potential impact for patients," said Jacob Van Naarden, executive vice president and president of Lilly Oncology. "With robust efficacy and safety evidence from the only study of its kind in the post-covalent BTK inhibitor treatment setting, we're proud to now offer this therapy to more patients with CLL or SLL at an earlier stage of their treatment plan."

What is Jayprica?

Jayprica is a non-covalent (reversible) BTK inhibitor approved by FDA and is a highly selective kinase inhibitor utilizing novel non-covalent binding mechanisms to extend the benefits of targeting BTK pathways in patients with relapsed or refractory CLL/SLL who were previously treated with a covalent BTK inhibitor.¹

With FDA’s approval to extend its indication, Jayprica is now approved for adults with CLL/SLL who have previously been treated with a covalent BTK inhibitor and for adult patients with relapsed or refractory (R/R) mantle cell lymphoma (MCL) following at least two lines of systemic therapy, including a BTK inhibitor.¹

"For CLL or SLL patients who progress following treatment with an irreversible or covalently binding BTK inhibitor, having additional therapeutic options is critical," said Brian Koffman, M.D., co-founder and chief medical officer emeritus at CLL Society. "With this approval, physicians and patients can stay in the same broad class of medicines with a treatment that offers meaningful impact on patient outcomes, saving the potential to use medicines with different targets for later therapy."

What was Jayprica’s Approval for extended indication based on?

Jayprica’s approval for its extended indication was based off results gathered from the Bruin CLL-321 trial. Bruin CLL-321 is a Phase III, randomized, open-label study of Jaypirca compared against investigator's choice of idelalisib plus rituximab (IdelaR) or bendamustine plus rituximab (BR) in covalent Bruton tyrosine kinase (BTK) inhibitor pre-treated patients with CLL or SLL.¹

The trial's primary endpoint was progression-free survival, per the 2018 International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria and was assessed by a blinded independent review committee. The trial’s secondary endpoints include progression-free survival, as assessed by investigator, overall response rate, duration of response, event-free survival, overall survival, and time to next treatment.¹

"Pirtobrutinib is the only medicine in CLL or SLL that has been prospectively studied in a randomized trial of patients previously treated with a covalent BTK inhibitor, and I am excited to see this expanded FDA approval recognize the benefit it can deliver to this broader group of patients," said Jeff Sharman, M.D., disease chair, Hematology Executive Committees, SCRI at Willamette Valley Cancer Institute and Research Center, and one of the principal investigators of the Bruin CLL-321 trial. "When covalent BTK inhibitors are no longer an option due to disease progression or intolerance, pirtobrutinib enables physicians to extend the benefits of targeting the BTK pathway, offering continuity in the CLL or SLL treatment experience."

Sources

1. U.S. FDA approves expanded indication for Lilly's Jaypirca (pirtobrutinib), the first and only non-covalent (reversible) BTK inhibitor, for adults with relapsed or refractory CLL/SLL previously treated with a covalent BTK inhibitor Eli Lilly and Company December 3, 2025 https://investor.lilly.com/news-releases/news-release-details/us-fda-approves-expanded-indication-lillys-jaypirca