Bristol Myers Squibb Announces Japanese Approval of Breyanzi (lisocabtagene maraleucel), a CD19-Directed CAR T-Cell Therapy, for Relapsed or Refractory Large B-Cell Lymphoma and Follicular Lymphoma

March 28, 2021/BioonBIOON/-- Bristol-Myers Squibb (BMS) recently announced that the Japanese Ministry of Health, Labour and Welfare (MHLW) has approved Breyanzi (lisocabtagene maraleucel, liso-cel), a CD19-directed chimeric antigen receptor (CAR) T-cell therapy, for the treatment of: (1) patients with relapsed or refractory large B-cell lymphoma (R/R LBCL); and (2) patients with relapsed or refractory follicular lymphoma (R/R FL).

It is particularly worth noting that, just recently, Bristol-Myers Squibb’s other CAR-T cell therapy, Abecma (ide-cel), received U.S.FDAApproved for the treatment of adult patients with relapsed or refractory multiple myeloma (R/R MM), this is the world’s first BCMA-directed CAR-T therapy!

Breyanzi is the fourth CD19-directed CAR-T cell therapy approved for marketing globally. The three previously marketed CD19 CAR-T cell therapies are:NovartisKymriah (tisagenlecleucel), Gilead Sciences’ Yescarta (axicabtagene ciloleucel), and Tecartus (brexucabtagene autoleucel).

Breyanzi is an autologous, CD19-directed CAR-T cell therapy with a defined composition and a 4-1BB co-stimulatory domain. Breyanzi consists of purified CD8+ and CD4+ T cells in a specific ratio (1:1), and 4-1BB signaling enhances the expansion and persistence of Breyanzi. Breyanzi offers a potentially curative treatment option, with a single dose containing 50–100 × 10⁶ CAR-positive viable T cells.

Breyanzi (liso-cel) was developed by Juno Therapeutics, which Celgene acquired in January 2018 for $9 billion. Bristol-Myers Squibb subsequently completed its $74 billion acquisition of Celgene in November 2019. Breyanzi is a CD19-directed CAR-T cell therapy utilizing 4-1BB as the co-stimulatory domain, featuring a precisely defined 1:1 ratio of CD4+ to CD8+ CAR-T cells. Breyanzi represents a potential best-in-class CD19-directed CAR-T therapy.

In February 2021, Breyanzi received the world’s first regulatory approval in the United States for the treatment of adult patients with relapsed or refractory large B-cell lymphoma (R/R LBCL) who had previously undergone 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 (HGBL), primary mediastinal large B-cell lymphoma (PMBCL), and grade 3B follicular lymphoma. Breyanzi is not indicated for the treatment of patients with primary central nervous system (CNS) lymphoma.

Currently, the Marketing Authorization Application (MAA) for Breyanzi is also under review by the European Medicines Agency (EMA). Previously, the EMA granted Breyanzi Priority Medicines (PRIME) designation for the treatment of relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL).

In Japan, the regulatory approval of Breyanzi was based on efficacy and safety data from the TRANSCEND NHL 001 trial conducted in patients with relapsed or refractory (R/R) B-cell non-Hodgkin lymphoma (B-NHL) and the TRANSCEND WORLD trial conducted in patients with R/R aggressive B-cell NHL.

——TRANSCEND NHL 001 Trial: In the primary efficacy evaluation population (n=133), the primary endpoint overall response rate (ORR) was 74.4% (95% CI: 66.2–81.6; data cutoff date: April 12, 2019), with the lower bound of the 95% CI exceeding the protocol-specified threshold of ORR=40%. Furthermore, in the efficacy analysis population receiving anti-CD19 CAR-T cell therapy (n=256), the ORR was 72.7% (95% CI: 66.8–78.0; data cutoff date: August 12, 2019).

——TRANSCEND WORLD Trial: Among 34 patients treated with Breyanzi, the primary endpoint objective response rate (ORR) was 58.8% (95% CI: 40.7–75.4; data cutoff date: September 13, 2019), which was statistically significant compared with the 40% threshold. Furthermore, the ORR in the 10 Japanese patients was 70.0% (95% CI: 34.8–93.3). Additionally, as of the data cutoff date of June 19, 2020, the ORRs in the overall study population (n=46) and in the 10 Japanese patients were 63.0% (95% CI: 47.5–76.8) and 70.0% (95% CI: 34.8–93.3), respectively.

—Safety: (1) In the TRANSCEND NHL 001 trial, safety was assessed in 269 patients treated with Breyanzi; adverse reactions occurred in 201 patients, including cytokine release syndrome (CRS, 42.0%), fatigue (17.8%), and neutropenia (16.4%),Anemia(13.8%), headache (13.4%), thrombocytopenia (11.5%), confusion (11.5%), tremor (11.2%), hypotension (10.4%). (2) In the TRANSCEND WORLD trial, 42 out of 46 patients (including 10 Japanese patients) experiencedAdverse Reactions, including neutropenia (52.2%), cytokine release syndrome (41.3%), anemia (39.1%), thrombocytopenia (39.1%), fever (39.1%), leukopenia (23.9%), confusion (15.2%), fatigue (13.0%), and febrile neutropenia (13.0%). (Bioon.com)

Original Source: Japan’s Ministry of Health, Labour and Welfareapproves Breyanzi, a New CAR T Cell Therapy