Application based on Phase 3 TRANSFORM study in which Breyanzi outperformed the current standard of care with demonstrated statistically significant improvement in event-free survival and a well-established safety profile
– Bristol Myers Squibb (NYSE: BMY) today announced that the European Medicines Agency (EMA) has validated its type II variation application for extension of the indication for Breyanzi (lisocabtagene maraleucel) to treat adult patients with diffuse large B-cell lymphoma (DLBCL), high grade B-cell lymphoma (HGBCL), primary mediastinal large B-cell lymphoma (PMBCL) and follicular lymphoma grade 3B (FL3B), who are refractory or have relapsed within 12 months of initial therapy and are candidates for haematopoietic stem cell transplant (HSCT). Validation of the application confirms the submission is complete and begins the EMA’s centralized review procedure.
“Rates of relapsed or refractory large B-cell lymphoma after first-line therapy are very high and few patients are able to benefit from stem cell transplant, which has been the second-line standard of care for nearly 30 years,” said Anne Kerber, senior vice president, Cell Therapy Development, Bristol Myers Squibb. “We look forward to working with the European Medicines Agency with the goal of establishing Breyanzi as a new second-line standard of care for people living with relapsed or refractory large B-cell lymphoma and, ultimately, bringing the curative potential of cell therapy to more patients.”
The type II variation is supported by data from the pivotal Phase 3 TRANSFORM study evaluating Breyanzi as a second-line treatment in adults with relapsed or refractory LBCL compared to the standard of care consisting of salvage chemotherapy followed by high-dose chemotherapy plus HSCT. In the study, Breyanzi significantly improved event-free survival (EFS) compared to standard of care, the study’s primary endpoint, and demonstrated clinically meaningful and statistically significant improvements in complete response rates and progression-free survival compared to standard of care. Breyanzi exhibited a well-established safety profile with very low rates of severe cytokine release syndrome (CRS) and neurologic events, and no new safety signals were observed in this second-line setting, consistent with the safety profile observed with Breyanzi in the third-line plus setting.
LBCL is an aggressive blood cancer and the most common type of non-Hodgkin lymphoma. Approximately 40% of patients will have disease that is refractory to or relapses after first-line treatment. High-dose chemotherapy followed by autologous stem cell transplant has been the mainstay of care in the second-line setting and historically has been the only potential for cure after failure of first-line treatment. While an estimated 50% of patients with primary refractory or relapsed disease are considered candidates for a stem cell transplant, only about 25% of these patients are able to receive stem cell transplant.
A supplemental Biologics License Application for Breyanzi for the treatment of relapsed or refractory LBCL after failure of first-line therapy is currently under Priority Review with the U.S. Food and Drug Administration (FDA), with an assigned Prescription Drug User Fee Act (PDUFA) goal date of June 24, 2022. A New Drug Application for Breyanzi for the second-line treatment of patients with relapsed or refractory LBCL is also under review with Japan’s Ministry of Health, Labour and Welfare.
Breyanzi, a differentiated CD-19 directed CAR T cell therapy, is currently approved in the European Union for the treatment of adult patients with relapsed or refractory (R/R) diffuse DLBCL, primary mediastinal large B-cell lymphoma PMBCL, and FL3B after two or more lines of systemic therapy. Breyanzi is not approved in any region for the second-line treatment of LBCL.
TRANSFORM (NCT03575351) is a pivotal, global, randomized, multicenter Phase 3 trial evaluating Breyanzi compared to the current standard of care (platinum-based salvage chemotherapy followed by high-dose chemotherapy and HSCT in patients responding to salvage chemotherapy) in patients with large B-cell lymphoma that was primary refractory or relapsed within 12 months after CD20-antibody and anthracycline containing first-line therapy. Patients were randomized to receive Breyanzi or standard of care salvage therapy, including rituximab plus dexamethasone, high-dose cytarabine, and cisplatin (R-DHAP), rituximab plus ifosfamide, carboplatin and etoposide (R-ICE), or rituximab plus gemcitabine, dexamethasone and cisplatin (R-GDP) per the investigators’ choice before proceeding to high-dose chemotherapy (HDCT) and hematopoietic stem cell transplant (HSCT). The primary endpoint of the study was event-free survival, defined as time from randomization to death from any cause, progressive disease, failure to achieve complete response or partial response, or start of new antineoplastic therapy due to efficacy concerns, whichever occurs first. Complete response rate was a key secondary endpoint response.
Breyanzi is a CD-19 directed chimeric antigen receptor (CAR) T cell therapy, administered as a defined composition to reduce variability of the CD8 and CD4 component dose. Breyanzi has a 4-1BB costimulatory domain which enhances the expansion and persistence of the CAR T cells. Breyanzi is approved by the U.S. Food and Drug Administration for the treatment of adult patients with relapsed or refractory LBCL after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (including DLBCL arising from indolent lymphoma), high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, and follicular lymphoma grade 3B.
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