Eli Lilly and Company announced that Jaypirca (pirtobrutinib), a non-covalent (reversible) Bruton’s tyrosine kinase (BTK) inhibitor, has received a positive opinion from the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) for the treatment of adult patients with relapsed or refractory chronic lymphocytic leukemia (CLL) who have received prior treatment 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.
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.
Paolo Ghia
The European Commission is currently taking final action on the application for the use of Jaypirca in patients with relapsed or refractory CLL who have received prior treatment with a BTK inhibitor as a result of this favorable view. Within the next month or two, the European Commission is anticipated to make a decision. Additionally, the European Medicines Agency (EMA) has already granted Jaypirca a conditional marketing authorization to treat adult patients with relapsed or refractory MCL who have already received treatment with a BTK inhibitor.
Data from the BRUIN CLL-321 clinical trial, the first randomized Phase 3 research in CLL ever carried out entirely in patients who had previously received treatment with a BTK inhibitor, provide credence to the positive conclusion. Based on an independent review committee (IRC) assessment, the study’s primary endpoint of progression-free survival (PFS) was met at the predetermined time of final analysis (Aug. 29, 2023), indicating that pirtobrutinib was superior to the investigator’s choice of bendamustine plus rituximab (BR) or idelalisib plus rituximab (IdelaR), both of which are global standards of care. One In line with the primary analysis, pirtobrutinib decreased the risk of disease progression or death by 46% when compared to IdelaR or BR at an updated analysis (Aug. 29, 2024) (median PFS: 14.0 vs. 8.7 months). PFS findings were consistent across important subgroups, such as patients who had previously received venetoclax, and subgroups linked to poor prognosis, such as those with complex karyotype, unmutated IGHV status, TP53 mutations, and/or 17p deletions. Furthermore, the trial’s predetermined, descriptive secondary goal, the median time to next treatment or death (TTNT), which can be used as a proxy for disease control outcomes, was 24 months as opposed to the control arm’s 11 months (63% improvement; HR=0.37 [95% CI, 0.25-0.52]). Including adverse events of particular concern, the overall safety profile of patients receiving pirtobrutinib in BRUIN CLL-321 was in line with safety information from the Phase 1/2 BRUIN research. Across all grades, neutropenia, exhaustion, diarrhea, anemia, rash, and contusion were the most frequent adverse effects.
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In December 2024, the BRUIN CLL-321 study’s findings were showcased at the Annual Meeting and Exposition of the American Society of Hematology (ASH).
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,
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.
Jacob Van Naarden
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The U.S. Food and Drug Administration’s (FDA) Accelerated Approval pathway approved Jaypirca in 2023 for the treatment of adult patients with relapsed or refractory MCL following at least two lines of systemic therapy, including a BTK inhibitor, as well as adult patients with CLL or small lymphocytic lymphoma (SLL) who have received at least two prior lines of therapy, including a BTK inhibitor and a BCL-2 inhibitor. This is in addition to the conditional approval in the EU for MCL and the positive opinion in CLL. For CLL/SLL patients worldwide, including in the US, Lilly has filed supplementary marketing applications for Jaypirca in the post-BTK inhibitor context.
BRUIN CLL-321
In BTK inhibitor-pretreated patients with small lymphocytic lymphoma (SLL) or chronic lymphocytic leukemia (CLL), BRUIN CLL-321 is a Phase 3, randomized, open-label research comparing pirtobrutinib to the investigator’s choice of bendamustine plus rituximab (BR) or idelalisib plus rituximab (IdelaR). 238 individuals were recruited for the trial and were randomized 1:1 to receive either BR or IdelaR at the labeled doses or pirtobrutinib (200 mg orally, once daily) at the investigator’s decision. The primary objective of this trial is progression-free survival (PFS), as determined by the blinded independent review committee (IRC) in accordance with the 2018 International Workshop on Chronic Lymphocytic Leukemia (iwCLL) standards. Event-free survival, overall survival (OS) and time to next treatment (TTNT), safety and tolerability, patient-reported outcomes (PRO), overall response rate (ORR) and duration of response (DoR), and PFS as determined by the investigator are examples of secondary endpoints.
Source: Eli Lilly and Company – News
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