Fosun Kite's Yescarta Set to Become China's First Approved CAR-T Therapy

Author:Pearls

According to the official website of the National Medical Products Administration (NMPA), the marketing authorization application (Acceptance No.: CXSS2000006) in China for Fosun Kite Biotechnology Co., Ltd.'s CD19-targeted autologous chimeric antigen receptor (CAR) T-cell therapy, axicabtagene ciloleucel injection (axicabtagene ciloleucel), is currently in the "under review" stage. It is expected to be approved for marketing by the NMPA in the near future, and will become the first CAR-T therapy approved for marketing in China.

Axicabtagene ciloleucel injection is a CD19-targeted, genetically modified autologous CAR-T cell injection developed by Gilead/Kite Pharma. Specifically, T cells are extracted from the patient's blood and genetically modified in vitro to equip them with a "chimeric antigen receptor" (CAR) that recognizes the CD19 antigen on the surface of cancer cells, thereby enabling these cells to target the CD19 antigen highly expressed on tumor cells. Subsequently, these modified cells are extensively expanded and reinfused into the patient to enhance the in vivo survival rate of the CAR-T cells. Once established in the patient's body, the CAR-T cells continue to proliferate, ultimately achieving the targeted attack on cancer cells.

In October 2017, axicabtagene ciloleucel injection received FDA approval for marketing (trade name: Yescarta) for the treatment of patients with relapsed or refractory large B-cell lymphoma who have received two or more prior lines of systemic therapy, including: diffuse large B-cell lymphoma (DLBCL) not otherwise specified (NOS), primary mediastinal B-cell lymphoma (PMBCL), high-grade B-cell lymphoma, and DLBCL transformed from follicular lymphoma. Yescarta is the second CAR-T therapy approved by the FDA and the first CAR-T therapy indicated for non-Hodgkin lymphoma.

In August 2018, Yescarta was approved for marketing in the European Union. In March 2021, Yescarta received accelerated approval from the U.S. FDA for the treatment of adult patients with relapsed or refractory follicular lymphoma (FL) who have received two or more prior lines of systemic therapy.

In early 2017, Fosun Kite licensed Yescarta from U.S.-based Kite Pharma, obtaining full technology licensing and commercialization rights in China (including Hong Kong and Macau), while conducting localized manufacturing within mainland China (excluding Hong Kong, Macau, and Taiwan).

After completing the bridging clinical trial in China for the treatment of relapsed or refractory large B-cell lymphoma in adults, Fosun Kite submitted a marketing authorization application in China in February 2020 for axicabtagene ciloleucel injection for the treatment of relapsed or refractory large B-cell lymphoma in adults, 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. The application was granted priority review by the Center for Drug Evaluation (CDE) on March 13.

Currently, five CAR-T cell therapies have been approved globally: four targeting CD19 and one targeting BCMA. They are Novartis' Kymriah (approved in August 2017), Gilead's Yescarta and Tecartus (approved in October 2017 and July 2020, respectively), and Bristol Myers Squibb's Breyanzi and Abecma (approved in February 2021 and March 2021, respectively).

In 2020, the global sales of Tecartus, Yescarta, and Kymriah were $44 million, $563 million, and $474 million, respectively.

In China, as many as 36 CAR-T therapies have entered clinical trials. In addition to Yescarta, which is expected to receive marketing approval shortly, JW Therapeutics’ CD19-targeted CAR-T therapy, relmacabtagene autoleucel, filed for marketing approval on June 29, 2020, and is currently under regulatory review. Novartis’ Kymriah is currently in Phase III clinical trials, while Legend Biotech’s BCMA-targeted CAR-T therapy is in Phase II clinical trials.

In terms of targets, CD19-targeted CAR-T products currently under development in China account for the largest number, totaling 23, followed by BCMA-targeted products with 5. Additionally, Shanghai Ucart Biotech, Henrui Dascience, and Gracell Biotechnologies are developing dual-target CAR-T therapies.