Daiichi Sankyo Announces Japanese Approval of Yescarta (axicabtagene ciloleucel), a CD19-Directed CAR T-Cell Therapy, for Relapsed/Refractory Large B-Cell Lymphoma

January 26, 2021/Bio ValleyBIOON/--Daiichi Sankyo recently announced that the Japanese Ministry of Health, Labour and Welfare (MHLW) has approved Yescarta (axicabtagene ciloleucel), a CD19-directed chimeric antigen receptor (CAR) T-cell therapy, for the treatment of adult patients with certain relapsed/refractory large B-cell lymphoma (LBCL).

Yescarta has been approved in Japan for the treatment of relapsed/refractory diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBCL), transformed follicular lymphoma (tFL), and high-grade B-cell lymphoma (HGBL). The use of Yescarta is limited to: (1) patients who have not previously received CD19 CAR-positive T-cell infusion therapy; (2) patients who have previously received two or more lines of therapy (including chemotherapy or autologousStem Cellstransplantation); (3) ineligible to receive autologousStem CellsTransplant patients.

Yescarta, developed by Kite Pharma, a cell therapy company under Gilead Sciences, was licensed to Daiichi Sankyo in January 2017 for exclusive rights to develop, manufacture, and commercialize this CD19 CAR-T therapy in Japan.

In Japan, the approval of Yescarta was based on a global pivotal study conducted by KiteClinical Trials(ZUMA-1) and the results of a Phase 2 clinical study conducted by Daiichi Sankyo. In a Japanese Phase 2, open-label, single-arm study, the efficacy and safety of Yescarta at the same dose as in the ZUMA-1 study (2.0 x 10^6 cells/kg) were evaluated in 16 Japanese patients with relapsed or refractory large B-cell lymphoma (including DLBCL, PMBCL, tFL, and HGBL). The results showed that the primary endpoint of the study—The objective response rate (ORR) was 86.7% (95% CI: 59.5–98.3%).

The overall safety and tolerability profile of Yescarta in the Japanese trial was consistent with that observed in ZUMA-1. No dose-limiting toxicities were observed. All patients experienced treatment-emergent adverse events (TEAEs) of grade ≥3, most commonly neutropenia (81.3%), lymphopenia (81.3%), and thrombocytopenia (62.5%). Cytokine release syndrome (CRS), a typical TEAE associated with CAR T-cell therapy, occurred in 81.3% of patients (all grades), including one case (6.3%) of grade ≥3 CRS. Neurological events, another typical TEAE associated with CAR T-cell therapy, were not observed.

Unlike conventional small-molecule or biologic therapies, CAR-T therapy is a living T-cell therapeutic product. The mechanism of Yescarta involves genetically modifying the patient’s T cells to express a chimeric antigen receptor (CAR) designed to target the antigen CD19, which is expressed on various hematologicTumorAntigenic proteins on the cell surface, including B-cell lymphoma andLeukemiaCell.

Yescarta was approved in the United States in October 2017FDAApproved as the first CAR-T cell therapy for adult patients with relapsed or refractory large B-cell lymphoma (LBCL). The specific indication is for the treatment of adult patients with relapsed or refractory LBCL who have received two or more prior lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL), primary mediastinal large B-cell lymphoma (PMBCL), high-grade B-cell lymphoma (HGBL), and DLBCL arising from follicular lymphoma (FL) (i.e., transformed FL, tFL). Yescarta is not indicated for the treatment of primary central nervous system lymphoma.

In China, Yescarta (axicabtagene ciloleucel injection [proposed], code FKC876) is being developed by Fosun Kite Biotechnology Co., Ltd. (FOSUN Kite), a joint venture established by Shanghai Fosun Pharmaceutical Group and Kite Pharma. In mid-March this year, Fosun Kite announced that the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) had included the New Drug Application (NDA) for axicabtagene ciloleucel injection (proposed), a CAR-T cell therapy product, in the priority review program. The therapy is indicated for adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal B-cell lymphoma (PMBCL), high-grade B-cell lymphoma, and DLBCL transformed from follicular lymphoma.

Yikaililunsai Injection (code FKC876) is a CD19-targeted autologous CAR-T cell therapy product, for which Fosun Kite has licensed the Yescarta (axicabtagene ciloleucel) technology from Kite Pharma and obtained authorization for localized production in China.

This product is the first CAR-T cell therapy product that Fosun Kite has advanced toward commercialization in China, and it is also the first CAR-T cell therapy product for which the National Medical Products Administration (NMPA) has formally accepted a marketing application. As a completely newTumorAs a treatment option, FKC876 can bring new hope and opportunities for patients in China with relapsed or refractory large B-cell lymphoma who have received second-line or later systemic therapy. (Bioon.com)

Original source: YESCARTA®approved in Japan for Treatment of Patients with Relapsed/Refractory Large B-Cell Lymphomas