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 two lines of systemic therapy, including a BTK inhibitor.
As a noncovalent BTK inhibitor, pirtobrutinib is able to restore BTK inhibition in patients previously treated with covalent BTK inhibitors (e.g. acalabrutinib, ibrutinib, zanubrutinib). This enables continuous targeting of the BTK signaling 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 enrolled 120 patients with MCL previously treated with a BTK inhibitor.
Study participants received pirtobrutinib 200 mg once daily until disease progression or unacceptable toxicity. Efficacy measures included overall response rate (ORR) and duration of response (DOR).
The 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 determined). The Kaplan-Meier estimate for the DOR rate at 6 months was 65.3% (95% CI: 49.8-77.1).
The most common side effects reported with Jaypirca were fatigue, musculoskeletal pain, diarrhea, edema, shortness of breath, pneumonia and bruising. Grade 3 or 4 laboratory abnormalities included decreased neutrophil count, decreased lymphocyte count, and decreased platelet count.
“These data suggest that Jaypirca may provide efficacy in patients previously treated with a covalent BTK inhibitor, potentially extending the time that patients can 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 significantly impact the treatment paradigm for relapsed and refractory MCL patients.”
In a press release, Lilly announced that it is currently enrolling patients in a confirmatory Phase 3 study (BRUIN MCL-321; ClinicalTrials.gov identifier: NCT04662255) comparing Jaypirca to other FDA-approved BTK inhibitors.
Jaypirca is available as 50 mg and 100 mg tablets. It is expected to be available in the coming weeks.
References
- The US FDA approves Jaypirca (pirtobrutinib), the first and only noncovalent (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. Press release. January 27, 2023. https://www.prnewswire.com/news-releases/us-fda-approves-jaypirca-pirtobrutinib-the-first-and-only-non-covalent-reversible-btk-inhibitor-f or-adult-patients-with-relapsed-or-refractory-mantle-cell-lymphoma-after-at least-two-lines-of-systemic-therapy-including-one-301732669.html
- Jaypirca. Package leaflet. Eli Lilly; 2023. Accessed January 27, 2023. https://pi.lilly.com/us/jaypirca-uspi.pdf?s=pi
This article originally appeared on MPR
