FDA Grants Priority Review to Bristol Myers Squibb’s sBLA for Breyanzi as Second-Line Therapy in Relapsed/Refractory Large B-Cell Lymphoma
Feb 18, 2022 03:33
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03:33
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News on February 17, 2022 /BioValleyBIOON/ -- Bristol-Myers Squibb (BMS) recently announced that the U.S. Food and Drug Administration (FDA) has accepted a supplemental Biologics License Application (sBLA) for CD19 CAR-T cell therapy Breyanzi (lisocabtagene maraleucel, liso-cel): second-line treatment for adult patients with relapsed or refractory large B-cell lymphoma (R/R LBCL). This sBLA aims to expand the current indication to include adult patients with R/R LBCL who receive Breyanzi treatment earlier after failing first-line treatment.FDAThe sBLA has been granted Priority Review, with a PDUFA goal date set for June 24, 2022.
For more than 20 years, salvage chemotherapy followed by high-dose chemotherapy andStem CellsTransplantation has always been a standard-of-care pillar for second-line relapsed or refractory LBCL patients, but only a small proportion of patients achieve long-term benefits through this method. In the pivotal Phase 3 TRANSFORM study,Breyanzi Outperforms Standard Care, Demonstrating Significant and Clinically Meaningful Improvement.These results have the potential to pave the way for a shift in treatment, where patients who experience disease recurrence or are unresponsive to first-line treatments can be treated with personalized CAR-T cell therapy, improving treatment outcomes.
This sBLA is based on the pre-specified interim analysis data from the pivotal Phase 3 TRANSFORM study (NCT03575351). This is a global, multicenter, randomized Phase 3 study evaluating the efficacy and safety of the CD19 CAR-T cell therapy Breyanzi (lisocabtagene maraleucel, liso-cel) as a second-line treatment for adult patients with relapsed or refractory large B-cell lymphoma (R/R LBCL). The interim analysis showed that the study met its primary endpoint and key secondary endpoints: in relapsed or refractory (R/R) LBCL patients eligible for HSCT, compared with the current standard-of-care regimen (salvage chemotherapy followed by high-dose chemotherapy [HDCT] and hematopoieticStem CellsCompared with transplantation [HSCT], Breyanzi has significant efficacy and good safety.
Specifically,With a median follow-up of 6.2 months, Breyanzi significantly extended event-free survival compared to standard care.(EFS, primary endpoint of the study): The median EFS in the Breyanzi treatment group was 10.1 months (95% CI: 6.1-NR), compared to 2.3 months (95% CI: 2.2-4.3) in the standard-of-care group.Breyanzi Reduced the Risk of EFS Events by 65% Compared to Standard Care（HR=0.349；p＜0.0001）。
Breyanzi is an autologous, CD19-directed, chimeric antigen receptor (CAR) T-cell therapy with a defined composition and 4-1BB co-stimulatory domain. Breyanzi consists of purified CD8+ and CD4+ T cells in a specific ratio (1:1), and the 4-1BB signaling enhances the expansion and persistence of Breyanzi.
In February 2020, Breyanzi was approved in the United StatesFDAApproved for the treatment of adult patients with R/R LBCL who have previously received two or more systemic therapies, including unspecified diffuse large B-cell lymphoma (DLBCL, including DLBCL arising from indolent lymphoma), high-grade B-cell lymphoma (HGBL), primary mediastinal large B-cell lymphoma (PMBCL), and follicular lymphoma grade 3B. Breyanzi is not indicated for the treatment of patients with primary central nervous system (CNS) lymphoma.
TRANSFORM Study Results Show for the First Time That, in Patients with Relapsed or Refractory LBCL, a Treatment Method Outperforms Standard High-Dose Chemotherapy andStem CellsTransplant therapy is more effective and, for the first time, demonstrates the potential of CD19-directed CAR-T cell therapy as a second-line treatment. Breyanzi has the potential to become the new standard of care for patients after first-line treatment failure.
Interim Analysis Results of the TRANSFORM Study
TRANSFORM is a global, randomized, multicenter study being conducted in adult patients with large B-cell lymphoma (LBCL) who are primary refractory or relapsed within 12 months of initial treatment and are eligible for stem cell transplantation. The study is evaluating the efficacy and safety of the CD19 CAR-T cell therapy Breyanzi (lisocabtagene maraleucel, liso-cel) as a second-line treatment, compared to the current standard of care, which includes high-dose chemotherapy (HDCT) and hematopoietic...Stem CellsTransplant [HSCT]) for comparison.
In the study, 184 patients with primary refractory LBCL or relapsed disease within ≤12 months after first-line treatment who were eligible for autologous HSCT were randomized to receive Breyanzi (n=92) or salvage chemotherapy followed by high-dose chemotherapy and autologous HSCT (n=92), which is considered the current standard of care for these patients. In this trial, which allowed crossover, 50 patients who failed to achieve remission after 9 weeks (three cycles of salvage chemotherapy) or at any time after disease progression following randomization crossed over from the standard-of-care group to receive Breyanzi.
Data Show That Most Patients (86%) Treated with Breyanzi Achieved Complete or Partial Remission, and 66% Achieved Complete Remission (CR). In Contrast, Less Than Half (48%) of Patients Receiving Standard Care Achieved Remission, and Only 39% of These Patients Achieved Complete Remission (p<0.0001). Compared with Standard Care, the Median Progression-Free Survival (PFS) for Breyanzi Treatment Was Significantly Longer (14.8 Months vs 5.7 Months [HR=0.406; p=0.0001]). Although Overall Survival (OS) Data Are Not Yet Mature, a Pre-Specified Interim Analysis Showed a Strong Trend Toward Improvement with Breyanzi Compared to Standard Care (HR=0.509, 95% CI: 0.258-1.004, p=0.0257).
In the study, Breyanzi demonstrated manageable safety, with very low incidence of severe cytokine release syndrome (CRS) and neurologic events (NE), and no new safety signals were observed in second-line treatment. No grade 4/5 CRS or NE was reported in the study. Any-grade CRS was reported in 49% of patients, with only one patient reporting grade 3 CRS. Among patients treated with Breyanzi, 12% reported any-grade NE, with four patients (4%) reporting grade 3 NE. (Bioon.com)