Pirtobrutinib

Eli Lilly's blood cancer pill Jaypirca sets itself apart from other BTK inhibitors as it can be used sequentially to others in its drug class. The company is set to apply for approval of Jaypirca as a first-line treatment in two types of lymphoma. By nailing the primary endpoint in a phase 3 trial, Eli Lilly's Bruton tyrosine kinase (BTK) inhibitor Jaypirca has come one step closer to reaching a broader group of patients with blood cancer.In a study of patients with treatment-naïve chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (CLL/SLL) who do not have 17p deletions, Jaypirca topped the chemoimmunotherapy combination of bendamustine plus rituximab.Jaypirca demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared to the chemoimmunotherapy, signaling “one of the most compelling effect sizes ever observed for a single agent BTK inhibitor in a front-line CLL study,” Lilly said in a Sept. 8 release.The data were not mature enough for a key secondary endpoint, overall survival (OS), but were trending “strongly in favor” of Jaypirca, Lilly said. The company added that it expects the OS assessment to be ready by the end of this year.The success of the study, which is dubbed BRUIN CLL-313, likely sets up Jaypirca for first-line use in the indications. In 2023, the FDA approved the daily oral treatment on an accelerated basis for CLL, SLL and mantle cell lymphoma after at least two prior lines of therapy, including one with another BTK inhibitor.The data from BRUIN CLL-313 will be presented at an upcoming medical conference and will be combined with results from another Jaypirca trial in the indications, BRUIN CLL-314, to back global regulatory submissions later this year, the company added. In the BRUIN CLL-314 study, the results of which were released in July, Jaypirca met its primary endpoint as a first-line treatment, measuring up to AbbVie and Johnson & Johnson’s Imbruvica, which was the first BTK inhibitor to reach the market.“The results from BRUIN CLL-313 are striking and provocative, across both PFS and OS endpoints, further demonstrating the potential of pirtobrutinib to be a meaningful treatment option for people with untreated CLL/SLL,” Jacob Van Naarden, the president of Lilly Oncology, said in a release.Jaypirca sets itself apart from three other BTK inhibitor blockbusters on the market—Imbruvica, AstraZeneca’s Calquence and BeOne Medicines’ Brukinsa—as it is a non-covalent BTK, meaning that it can be used sequentially to others in the class. Because Jaypirca binds to BTK differently, it can be used after patients experience disease progression while on another BTK inhibitor. The mechanism gives Jaypirca a unique opportunity to treat patients who have failed on another BTK inhibitor. Most blood cancer patients eventually progress on covalent BTK meds.While the recent trial results indicate Jaypirca’s value as a first-line treatment, that was “not the core value proposition of the drug,” Van Naarden told Fierce upon its initial approval. In the first half of 2025, Jaypirca generated sales of $215 million. By comparison, sales of Calquence and Brukinsa reached $3.1 billion and $2.6 billion, respectively, in 2024. Sales of Imbruvica, which reached their peak in 2021 at $9.8 billion, fell to $6.4 billion last year.  

Eli Lilly’s Jaypirca met the primary endpoint in a Phase 3 blood cancer trial, bringing the BTK inhibitor one step closer to a potential approval for previously untreated patients with a type of lymphoma. Jaypirca achieved a “highly statistically significant and clinically meaningful improvement” in progression-free survival compared to chemoimmunotherapy in patients with chronic lymphocytic leukemia or small lymphocytic lymphoma, Lilly announced on Monday. Lilly Oncology President Jacob Van Naarden called the results “striking and provocative” in a news release. Jaypirca won an accelerated approval in 2023 to treat CLL and SLL, but only for patients who have received at least two prior therapies. Van Naarden said in the news release that Eli Lilly wants to make Jaypirca “an option for a wider group of patients who might benefit.” Overall survival data were not yet mature in the CLL-313 study, but Lilly said they were “trending strongly in favor of” Jaypirca. The company expects to conduct a primary analysis for overall survival in 2026. Lilly said data from this trial, dubbed BRUIN CLL-313, and another called BRUIN CLL-314 would “form the basis for seeking label expansions in earlier lines of therapy,” but gave few details on Monday. It said it expects to begin global regulatory submissions “later this year.” Unlike the CLL-313 study, which tested Jaypirca against chemoimmunotherapy, the CLL-314 study pitted Jaypirca against Johnson & Johnson’s BTK inhibitor Imbruvica. That trial enrolled patients who were either treatment-naive, or who had received prior treatment but not with a BTK inhibitor. Lilly announced in July that Jaypirca met the primary endpoint of a non-inferior response rate compared to Imbruvica. The company also read out positive results in December from a trial in patients who had previously been treated with a covalent BTK inhibitor. Van Naarden said in the Monday news release that the latest results “continue to build the clinical evidence supporting the possible role of pirtobrutinib in a variety of CLL/SLL treatment settings.”