Eli Lilly and Company has announced that the U.S. Food and Drug Administration (FDA) has granted expanded approval for Jaypirca (pirtobrutinib) for adults with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) who have previously been treated with a covalent Bruton tyrosine kinase (BTK) inhibitor. The decision broadens the drug’s label to include patients earlier in their treatment journey and converts its December 2023 accelerated approval for later-line CLL/SLL into a full traditional approval.
The approval is based on data from BRUIN CLL-321, a randomized study that represents the first prospective trial evaluating a treatment specifically in patients with CLL or SLL who were previously treated with a covalent BTK inhibitor. These inhibitors — such as ibrutinib, acalabrutinib, or zanubrutinib — have transformed CLL and SLL care, but many patients develop intolerance or disease progression, creating an urgent need for additional therapeutic options.
“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 Dr. Jeff Sharman, Disease Chair for the Hematology Executive Committees at SCRI and one of the study’s principal investigators. “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.”
Jaypirca is the first and only FDA-approved non-covalent (reversible) BTK inhibitor. Unlike first-generation covalent BTK inhibitors that bind irreversibly to the BTK protein, Jaypirca uses a novel reversible binding mechanism that allows it to remain effective even when cancer cells develop resistance to earlier therapies. This selectivity and flexibility help maintain the therapeutic benefits of targeting BTK, a critical driver of CLL and SLL cell survival.
Jacob Van Naarden, executive vice president and president of Lilly Oncology, said the expanded approval confirms the company’s long-standing belief in the drug’s potential. “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,” he said. “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 at an earlier stage.”
Patient advocacy groups also welcomed the announcement, emphasizing the need for effective treatment options following resistance or intolerance to covalent BTK inhibitors. “For CLL or SLL patients who progress following treatment with an irreversible or covalently binding BTK inhibitor, having additional therapeutic options is critical,” said Dr. Brian Koffman, co-founder and chief medical officer emeritus of the 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.”
Lilly’s Jaypirca (available in 50 mg and 100 mg tablets) is expected to give physicians greater flexibility in sequencing therapies for CLL and SLL while providing a new opportunity to extend BTK-targeted treatment in patients who no longer respond to previous-generation drugs. The expanded approval underscores a growing trend toward precision drug design and the development of therapies that can overcome known mechanisms of resistance.
With this decision, the FDA continues to strengthen treatment pathways for CLL and SLL — two of the most common forms of adult leukemia — and support the introduction of innovative therapies capable of improving long-term patient outcomes.