On March 25, 2021 Bristol Myers Squibb K.K. reported that Japan’s Ministry of Health, Labour and Welfare (MHLW) approved Breyanzi (lisocabtagene maraleucel: liso-cel), a CD19-directed chimeric antigen receptor (CAR) T cell therapy for the treatment of patients with relapsed or refractory (R/R) large B-cell lymphoma1 and R/R follicular lymphoma (Press release, Bristol-Myers Squibb, MAR 25, 2021, View Source [SID1234577148]).2

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The approval is based on efficacy and safety from the TRANSCEND NHL 001 trial in patients with R/R B-cell non-Hodgkin lymphoma (NHL) and the TRANSCEND WORLD trial in patients with R/R aggressive B-cell NHL.

Large B-cell lymphoma comprises several disease types including diffuse large B-cell lymphoma (DLBCL). DLBCL is the most common form of non-Hodgkin lymphoma in Japan, accounting for 30-40% of all B-cell cases diagnosed,3 and is especially prevalent among people in their 60’s.4 There is currently no established standard-of-care treatment for patients with R/R large B-cell lymphoma,5 which underscores the need for new treatments for in this disease area. Follicular lymphoma accounts for 10-20% of all B-cell NHL cases in Japan. Patients initially respond to chemotherapy, but relapse is common, especially in advanced-stage patients.5 There is also no established standard-of-care treatment for patients with follicular lymphoma grade 3B.5

Jean-Christophe Barland, President and CEO of Bristol-Myers Squibb K.K. and Celgene K.K., said, "I am pleased that we have received regulatory approval in Japan for Breyanzi, our first CAR T cell therapy, which will allow us to provide a new treatment option for patients fighting relapsed or refractory large B-cell lymphoma and relapsed or refractory follicular lymphoma. In addition, we are filing an application for a further CAR T cell therapy to address more unmet medical needs. As a game-changer committed to ‘innovation with heart’, Bristol Myers Squibb will continue on its journey to help patients prevail over serious diseases."

Breyanzi is a chimeric antigen receptor T cell therapy designed to target CD19, which is expressed on the cell during normal B-cell development and maintained even after malignant transformation of B cells. Breyanzi aims to target CD19-expressing cells and is administered in a one-time infusion as a defined, purified composition to reduce variability of the CD8 and CD4 component dose. Breyanzi will be manufactured at Bristol Myers Squibb’s cellular immunotherapy manufacturing facility in Bothell, Washington and at a partner company facility in Japan.

Breyanzi was approved by the U.S. Food and Drug Administration on February 5, 2021 for the treatment of adult patients with relapsed or refractory large B-cell lymphoma (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. Breyanzi is not indicated for the treatment of patients with primary central nervous system lymphoma. Breyanzi has been granted Priority Medicines (PRIME) designation for relapsed or refractory DLBCL in the European Union and a Marketing Authorization Application is currently under review by the European Medicines Agency.

TRANSCEND NHL 001 / TRANSCEND WORLD Trial Key Results

In the TRANSCEND NHL 001 trial, of 133 subjects in the primary efficacy evaluation population, the overall response rate [95% CI], which was the primary endpoint, was 74.4% [66.2, 81.6] (April 12, 2019 data cutoff), and the lower limit of the 95% CI therefore exceeded the protocol-defined threshold overall response rate of 40%. In addition, the overall response rate [95% CI] in the 256 subjects in the efficacy analysis population treated with anti-CD19 CAR T cells was 72.7% [66.8, 78.0] (August 12, 2019 data cutoff). In the TRANSCEND WORLD trial, of 34 subjects who received BREYANZI, the overall response rate [95% CI], which was the primary endpoint, was 58.8% [40.7, 75.4] (September 13, 2019 data cutoff), which was statistically significant compared to the threshold value of 40%. In addition, the overall response rate [95% CI] in the 10 Japanese subjects was 70.0% [34.8, 93.3]. Moreover, the overall response rates [95% CIs] in the 46 subjects in the study population overall and in the 10 Japanese subjects at the June 19, 2020 data cutoff were 63.0% [47.5, 76.8] and 70.0% [34.8, 93.3], respectively.

In the TRANSCEND NHL 001 trial, 269 patients treated with Breyanzi were evaluated for safety. Adverse reactions occurred in 201 patients including cytokine release syndrome (42.0%), fatigue (17.8%), neutropenia (16.4%), anemia (13.8%), headache (13.4%), thrombocytopenia (11.5%), confusion (11.5%), tremor (11.2%), and hypotension (10.4%) (aggregated until approval). Adverse reactions occurred in 42 patients out of 46 (including 10 Japanese) treated with Breyanzi in the TRANSCEND WORLD trial. Adverse reactions included neutropenia (52.2%), cytokine releasesyndrome (41.3%), anemia (39.1%), thrombocytopenia (39.1%), pyrexia (39.1%), leukopenia (23.9%), confusion (15.2%), fatigue (13.0%), and febrile neutropenia (13.0%) (aggregated until approval).

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