Pirtobrutinib

In a phase 3 trial, Eli Lilly's non-covalent BTK inhibitor Jaypirca has matched up to AbbVie and Johnson & Johnson's covalent BTK inhibitor Imbruvica on overall response rate. The newest BTK inhibitor on the market, Eli Lilly’s Jaypirca, has shown its chops in a head-to-head battle against the oldest treatment in the class, AbbVie and Johnson & Johnson’s Imbruvica.A phase 3 trial of Jaypirca has met its primary endpoint in patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who were newly diagnosed or had never received BTK inhibitors.Lilly’s drug hit its mark, demonstrating that it matched up to Imbruvica in overall response rate (ORR) for both subpopulations in the study. The comparison also showed a nominal superiority for Jaypirca, although this analysis was not part of the trial's statistical plan. Data for progression-free survival (PFS) were not mature, but Lilly said they were trending in favor of Jaypirca. The trial, coded Bruin CLL-314, will undergo a formal PFS analysis with the goal of showing superiority in the future, the company added.“We launched the [Jaypirca] randomized development program with an ambitious suite of clinical trials, including head-to-head studies against modern standards of care and examinations of patient populations that reflect real world use, such as BTK inhibitor-pretreated patients,” Jacob Van Naarden, Lilly’s oncology chief, said in a statement. Jaypirca’s overall safety profile remained consistent with previously reported trials, and no detriment to patients' life expectancy was observed, according to Lilly. Detailed results from the study will be presented at a medical conference later this year, the company said.The company is waiting for results from another trial of Jaypirca, coded Bruin CLL-313, in CLL/SLL patients to apply for global approvals in the indication. That study, which pits Jaypirca against chemoimmunotherapy in treatment-naïve patients and uses PFS as the primary endpoint, is expected to read out later this year.In 2023, Jaypirca scored accelerated FDA nods to treat CLL, SLL and mantle cell lymphoma after at least two prior lines of therapy, including one with another BTK inhibitor. Jaypirca is unique in that it is a non-covalent, or reversible, BTK inhibitor, which can be used after treatment with the other three options in the class. Those BTKs—Imbruvica, AstraZeneca’s Calquence and BeOne Medicines' Brukinsa—are covalent and can’t be use sequentially.Jaypirca generated sales of $337 million in 2024, compared to $3.1 billion for Calquence, which reached the market in 2017, and $2.6 billion for Brukinsa, which was approved in 2019. Imbruvica, which scored its original FDA nod in 2013, generated $6.4 billion last year. Its sales peaked in 2021 at $9.8 billion. 

Pirtobrutinib met the primary endpoint of response rate non-inferiority, favoring pirtobrutinib with a nominal P-value for superiority < 0.05 Progression-free survival data was immature, but trending in favor of pirtobrutinib BRUIN CLL-314 is the first-ever head-to-head Phase 3 study versus a covalent BTK inhibitor to include treatment-naïve patients INDIANAPOLIS, IN, USA I July 29, 2025 I Eli Lilly and Company (NYSE: LLY ) today announced positive topline results from the Phase 3 BRUIN CLL-314 clinical trial of Jaypirca (pirtobrutinib), a non-covalent (reversible) Bruton’s tyrosine kinase (BTK) inhibitor, versus Imbruvica (ibrutinib), a covalent BTK inhibitor, in patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL). This study enrolled patients with treatment-naïve CLL/SLL and those who had been previously treated but were BTK inhibitor-naïve. The study met its primary endpoint of non-inferiority on overall response rate (ORR) as assessed by an independent review committee (IRC) in both the pre-treated and intent-to-treat populations. ORR favored pirtobrutinib with a nominal P-value for superiority 1 (p <0.05). Progression free survival (PFS), a key secondary endpoint, was not yet mature at this analysis, but was trending in favor of pirtobrutinib. A formal PFS analysis testing for superiority is planned at a future analysis. No detriment was observed for overall survival (OS). BRUIN CLL-314 is the first ever head-to-head trial versus ibrutinib in CLL to include treatment-naïve patients. This important subpopulation (n=225) had the longest follow-up and a particularly pronounced PFS effect size in favor of pirtobrutinib. The overall safety profile of pirtobrutinib in BRUIN CLL-314 was similar to previously reported trials. Detailed results will be presented at a medical congress later in 2025. “We launched the pirtobrutinib randomized development program with an ambitious suite of clinical trials, including head-to-head studies against modern standards of care and examinations of patient populations that reflect real world use, such as BTK inhibitor-pretreated patients,” said Jacob Van Naarden, executive vice president and president of Lilly Oncology. “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.” These data build on the previously reported positive results from the BRUIN Phase 1/2 trial and the Phase 3 BRUIN CLL-321 trial, the first randomized, controlled study ever conducted in an exclusively post-covalent BTK inhibitor population. The BRUIN CLL-313 Phase 3 study of pirtobrutinib versus chemoimmunotherapy in treatment naïve CLL/SLL is expected to read out later in 2025 and combined with the results of BRUIN CLL-314, will form the basis of regulatory submissions globally. For more information on the BRUIN Phase 3 clinical trial program, please visit clinicaltrials.gov . About BRUIN CLL-314 BRUIN CLL-314 is a Phase 3, randomized, open-label study of pirtobrutinib versus ibrutinib in patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) who were either treatment-naïve, or who were previously treated and were BTK inhibitor-naïve. The trial planned to enroll 650 patients who were randomized 1:1 to receive pirtobrutinib (200 mg orally, once daily) or ibrutinib (420 mg orally, once daily). The primary endpoint is overall response rate (ORR) as assessed by blinded independent review committee (IRC). Secondary endpoints include investigator and IRC assessed progression-free survival (PFS), duration of response (DoR) and event-free survival (EFS), and time to next treatment (TTNT), overall survival (OS), safety and tolerability, and patient-reported outcomes (PRO). About Jaypirca (pirtobrutinib) Jaypirca (pirtobrutinib, formerly known as LOXO-305) (pronounced jay-pihr-kaa) is a highly selective (300 times more selective for BTK versus 98% of other kinases tested in preclinical studies), non-covalent (reversible) inhibitor of the enzyme BTK. 2 BTK is a validated molecular target found across numerous B-cell leukemias and lymphomas including mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL). 3,4 Jaypirca is a U.S. FDA-approved oral prescription medicine, 100 mg or 50 mg tablets taken as a once-daily 200 mg dose with or without food until disease progression or unacceptable toxicity. INDICATIONS FOR JAYPIRCA (pirtobrutinib) Jaypirca is a kinase inhibitor indicated for the treatment of These indications are approved under accelerated approval based on response rate. Continued approval for these indications may be contingent upon verification and description of clinical benefit in a confirmatory trial. Please see Prescribing Information and Patient Information for Jaypirca. About Lilly Lilly is a medicine company turning science into healing to make life better for people around the world. We’ve been pioneering life-changing discoveries for nearly 150 years, and today our medicines help tens of millions of people across the globe. Harnessing the power of biotechnology, chemistry and genetic medicine, our scientists are urgently advancing new discoveries to solve some of the world’s most significant health challenges: redefining diabetes care; treating obesity and curtailing its most devastating long-term effects; advancing the fight against Alzheimer’s disease; providing solutions to some of the most debilitating immune system disorders; and transforming the most difficult-to-treat cancers into manageable diseases. With each step toward a healthier world, we’re motivated by one thing: making life better for millions more people. That includes delivering innovative clinical trials that reflect the diversity of our world and working to ensure our medicines are accessible and affordable. To learn more, visit Lilly.com and Lilly.com/news , or follow us on Facebook , Instagram , and LinkedIn . 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