The Food and Drug Administration (FDA) has granted accelerated approval to Jaypirca™ (pirtobrutinib) for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL) after at least 2 lines of systemic therapy, including a BTK inhibitor.
As a noncovalent inhibitor of BTK, pirtobrutinib is able to reestablish BTK inhibition in patients previously treated with covalent BTK inhibitors (eg, acalabrutinib, ibrutinib, zanubrutinib). This allows for continued targeting of the BTK pathway.
The accelerated approval was based on data from the phase 1/2 BRUIN trial (ClinicalTrials.gov Identifier: NCT03740529), an open-label, single-arm study that included 120 patients with MCL who were previously treated with a BTK inhibitor.
Study participants received pirtobrutinib 200mg once daily until disease progression or unacceptable toxicity. The efficacy measures included overall response rate (ORR) and duration of response (DOR).
Results showed an ORR of 50% (95% CI, 41-59); 13% of patients had a complete response and 38% of patients had a partial response. The median time to response was 1.8 months (range, 0.8-4.2 months) and the median DOR was 8.3 months (95% CI, 5.7, not established). The Kaplan-Meier estimate for the DOR rate at 6 months was 65.3% (95% CI, 49.8-77.1).
The most common adverse reactions reported with Jaypirca were fatigue, musculoskeletal pain, diarrhea, edema, dyspnea, pneumonia, and bruising. Grade 3 or 4 laboratory abnormalities included decreased neutrophil count, decreased lymphocyte count, and decreased platelet count.
“These data indicate that Jaypirca can provide efficacy in patients previously treated with a covalent BTK inhibitor, potentially extending the time patients may benefit from BTK inhibition therapy,” said Michael Wang, MD, Puddin Clarke Endowed Professor of Lymphoma and Myeloma at The University of Texas MD Anderson Cancer Center. “Jaypirca offers a new approach to targeting the BTK pathway following treatment with a covalent BTK inhibitor and has the potential to meaningfully impact the treatment paradigm for relapsed and refractory MCL patients.”
In a press statement, Lilly announced that a confirmatory phase 3 trial (BRUIN MCL-321; ClinicalTrials.gov Identifier: NCT04662255), which will compare Jaypirca to other FDA-approved BTK inhibitors, is currently enrolling patients.
Jaypirca is supplied as 50mg and 100mg tablets. It is expected to be available in the coming weeks.
- US FDA approves Jaypirca™ (pirtobrutinib), the first and only non-covalent (reversible) BTK inhibitor, for adult patients with relapsed or refractory mantle cell lymphoma after at least two lines of systemic therapy, including a BTK inhibitor. News release. January 27, 2023. https://www.prnewswire.com/news-releases/us-fda-approves-jaypirca-pirtobrutinib-the-first-and-only-non-covalent-reversible-btk-inhibitor-for-adult-patients-with-relapsed-or-refractory-mantle-cell-lymphoma-after-at-least-two-lines-of-systemic-therapy-including-a-301732669.html
- Jaypirca. Package insert. Eli Lilly; 2023. Accessed January 27, 2023. https://pi.lilly.com/us/jaypirca-uspi.pdf?s=pi