Transparency Submission

FDA Clearance: Jaypirca (pirtobrutinib) is a kinase inhibitor indicated for the treatment of: Adult patients with relapsed or refractory mantle cell lymphoma (MCL) after at least two lines of systemic therapy, including a BTKi. This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. Adult patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) who have received at least two prior lines of therapy, including a BTKi and a B-cell lymphoma 2 (BCL-2) inhibitor. This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. Please refer to the product prescribing information for the full FDA-approved indications and safety information for pirtobrutinib, available at http://pi.lilly.com/us/jaypirca-uspi.pdf.

Rationale for Requested Change: In this submission, we have included two data disclosures from the BRUIN trial which support the use of pirtobrutinib in patients intolerant to covalentBTK inhibitors. BRUIN is a global, multicenter, open-label, phase 1/2 trial that evaluates pirtobrutinib as a single agent in patients with previously-treated chronic lymphocytic leukemia, small lymphocytic lymphoma or non-Hodgkin’s lymphoma who have failed or are intolerant to standard of care (NCT03740529). The primary endpoint of the phase 2 portion of the study is overall response rate (ORR) by independent review committee. The first disclosure is a post-hoc analysis of patients from BRUIN with mantle cell lymphoma with documented intolerance to BKTi therapy. In this analysis, BTKi intolerance was defined as prior BTKi discontinuation due to persistent or recurrent adverse events as determined by the investigator. As of the data cutoff of July 29, 2022, a total of 773 patients were enrolled in the BRUIN study, including 21 patients with mantle cell lymphoma who had discontinued prior treatment with a BTKi due to intolerance. In these 21 patients with MCL and BTKi intolerance, the objective response rate was 81% (95% CI: 58, 95) with a best response of complete response in 9 patients (43%), partial response in 8 patients (38%), and stable disease in 1 patient (4.8%). The 18-month progression-free survival rate was 62% and the 18-month overall survival rate was 72% (95% CI: 46, 88). Pirtobrutinib monotherapy was well-tolerated. No patients who discontinued a prior BTK inhibitor due to a treatment-emergent adverse event had to discontinue pirtobrutinib for the same treatment-emergent adverse event (Shah, ASH 2022). The second disclosure reports updated efficacy and safety data in patients from BRUIN with mantle cell lymphoma. As of the data cutoff of May 5, 2023, a total of 778 patients were enrolled in the BRUIN study, including 152 patients with mantle cell lymphoma had received prior covalent BTKi therapy. In these 152 patients with MCL who previously discontinued a BTKi, the objective response rate was 49% (95% CI: 41, 58) with a best response of complete response in 24 patients (16%) and partial response in 51 patients (34%). In the 21 patients with MCL who discontinued their prior BTKi due to toxicity or reasons other than progressive disease, the objective response rate was 91%. (95% CI: 70, 99). Pirtobrutinib was well-tolerated with low rates of discontinuation due to drug-related toxicity (Cohen, ASH 2023) We welcome the opportunity to discuss these topics further or address any questions you may have. Thank you for your attention to this matter.