礼来宣布Jaypirca （pirtobrutinib）被CHMP推荐在欧盟批准用于既往用BTK抑制剂治疗的复发或难治性慢性淋巴细胞白血病（CLL）的成人患者

INDIANAPOLIS, Feb. 28, 2025 /PRNewswire/ -- Eli Lilly and Company (NYSE: LLY) announced today that the European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion for Jaypirca (pirtobrutinib), a non-covalent (reversible) Bruton's tyrosine kinase (BTK) inhibitor, for the treatment of adult patients with relapsed or refractory chronic lymphocytic leukemia (CLL) who have been previously treated with a BTK inhibitor.

"Results from the BRUIN CLL-321 trial show that Jaypirca delivers clinically meaningful outcomes in a post-BTK inhibitor setting with markedly prolonged time to next treatment, including in those with high-risk characteristics often associated with poor prognosis," said Paolo Ghia, M.D., professor, medical oncology, Università Vita-Salute San Raffaele and IRCCS Ospedale San Raffaele, Milano, Italy. "Jaypirca allows for continued targeting of the BTK pathway following treatment with a covalent BTK inhibitor and has the potential to be an important new option in a setting with significant unmet need. The CHMP opinion is an important step toward bringing Jaypirca to patients in the European Union."

Following this positive opinion, the application for the use of Jaypirca in patients with relapsed or refractory CLL who have been previously treated with a BTK inhibitor is now referred to the European Commission for final action. The European Commission's decision is expected in the next one to two months. Jaypirca has also previously received a conditional marketing authorization by the EMA for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL) who have been previously treated with a BTK inhibitor.

The positive opinion is supported by data from the BRUIN CLL-321 clinical trial, the first randomized Phase 3 study in CLL ever conducted exclusively in patients previously treated with a BTK inhibitor. The study's primary endpoint of progression-free survival (PFS) was met at the prespecified time of final analysis (Aug. 29, 2023), based on independent review committee (IRC) assessment, demonstrating pirtobrutinib was superior to investigator's choice of idelalisib plus rituximab (IdelaR) or bendamustine plus rituximab (BR), both global standards of care.1 At an updated analysis (Aug. 29, 2024), pirtobrutinib reduced the risk of disease progression or death by 46% compared to IdelaR or BR (median PFS: 14.0 vs. 8.7 months), consistent with the primary analysis. PFS results were consistent across key subgroups, including patients who received prior venetoclax and across subgroups associated with poor prognosis, including those with TP53 mutations and/or 17p deletions, unmutated IGHV status and complex karyotype. Additionally, the median time to next treatment or death (TTNT), a prespecified, descriptive secondary endpoint in the trial that can serve as a surrogate marker for disease control outcomes, was 24 months compared to the control arm of 11 months (63% improvement; HR=0.37 [95% CI, 0.25-0.52]). The overall safety profile for patients treated with pirtobrutinib in BRUIN CLL-321 was consistent with safety data from the Phase 1/2 BRUIN study, including adverse events of special interest. The most common adverse reactions of any grade were neutropenia, fatigue, diarrhea, anemia, rash, and contusion.

Results from the BRUIN CLL-321 study were presented at the American Society of Hematology (ASH) Annual Meeting and Exposition in December 2024.

"We are pleased to receive a positive opinion from the CHMP, signaling that the European Union may lead the way in broadening patient access to Jaypirca for those with relapsed or refractory CLL in the post-BTK inhibitor setting," said Jacob Van Naarden, executive vice president and president of Lilly Oncology. "There are currently no treatment options that have been specifically studied in a randomized Phase 3 trial in this patient population, and we are hopeful Jaypirca will be a meaningful new option for patients. We look forward to the European Commission's decision in the coming months."

In addition to this positive opinion in CLL and conditional approval in MCL in the EU, Jaypirca was approved in the U.S. in 2023 under the U.S. Food and Drug Administration's (FDA) Accelerated Approval pathway for the treatment of adult patients with relapsed or refractory MCL after at least two lines of systemic therapy, including a BTK inhibitor, and adult patients with CLL or small lymphocytic lymphoma (SLL) who have received at least two prior lines of therapy including a BTK inhibitor and BCL-2 inhibitor. Lilly has submitted supplemental marketing applications for Jaypirca in the post-BTK inhibitor setting for CLL/SLL patients around the globe, including in the U.S.