Axicabtagene Ciloleucel Injection (brand name: Yescarta) was recently granted marketing approval by China National Medical Products Administration (NMPA)1, marking the first approved chimeric antigen receptor T-cell (CAR-T) therapy in China and the sixth globally.
The therapy is developed by Fosun Kite Biotechnology Co., Ltd. (hereinafter referred to as Fosun Kite), a joint venture of Shanghai Fosun Pharmaceutical (Group) Co., Ltd. and US Kite Pharma.
Indication
Yescarta is indicated for adult patients with relapsed or refractory large B-cell lymphoma (r/r LBCL) after two or more lines of systemic therapy. Specific indications are diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma (PMBCL), high-grade B-cell lymphoma and DLBCL arising from follicular lymphoma.2
How the Therapy Works
Yescarata is a CD19-directed genetically modified autologous T cell immunotherapy. It binds to CD19-expressing cancer cells and normal B cells. Studies demonstrated that following anti-CD19 CAR T cell engagement with CD19-expressing target cells, the CD28 and CD3-zeta co-stimulatory domains activate downstream signaling cascades that lead to T cell activation, proliferation, acquisition of effector functions and secretion of inflammatory cytokines and chemokines. This sequence of events leads to killing of CD19-expressing cells.3
Marketing Approval Expedited by Priority Review
The successful entry of Yescarta into China market benefits from its manufacturer's strong biotechnology and China's reform of the drug review and approval system. The product drew upon on the technology and experience from the development of Kite Pharma's Yescarta, a precedent CAR-T product approved by the US Food and Drug Administration (FDA).
Timeline for Developing and Registering Axicabtagene Ciloleucel Injection (Yescarta) in China
CAR-T Therapy in China: Promising Future with Challenges
As the trailblazer in China's CAR-T market, Fosun Kite's Yescarta offers an effective treatment to patients. Many Chinese pharma companies thus strengthen their confidence in CAR-T therapies and are pouring efforts into developing them. Yet, the road to success won't be smooth or straightforward.
The pharma companies developing CAR-T therapies seem to take a keen interest in CD-19. In China, the number of in progress CAR-T trials involving CD-19 reached 175 among the 357 total by the first half of 2020.4 Therefore, the competition is expected to be intense, especially for the products with the same target.
Though CAR-T is a magnet for pharma companies, developing and commercializing the therapy is never a piece of cake. Each patient should use customized batch of products. Also, work is demanding with each batch in terms of manufacturing, quality control, cold chain transportation and services.
CAR-T therapy also faces the challenge of how to reach more people. As a personalized treatment, CAR-T therapy is not appropriate for mass production, which cannot be an approach to cutting costs.
The current costs of CAR-T therapy may daunt the patients. JAMA Oncology estimated that the mean expected total costs for Kymriah and Yescarta per patient are $510,963 and $402,647, respectively.5 As for Yescarta, its price in China has not been announced by Fosun Kite yet.
Lastly, China might rein in the overheating development of me-too antineoplastic drugs. Currently CDE is consulting on the Guideline on the Research & Development during Clinical Trials of Clinical Value-Oriented Antineoplastic Drugs6. According to the consultation draft, the new drug research and development should aim to provide patients with better treatment options. If not referring to the best support care (BSC), the clinical trial, which even reaches the preset research goal, can neither prove that the trial drug can meet patients' clinical needs, nor prove the drug's therapeutic effect for patients.
The statement implies a higher requirement for new drugs, especially me-too drugs; and China tends to guide local pharmaceutical companies to reduce investment in developing new drugs with the same hot biological targets. Thus, players in CAR-T market may not be as many as the companies which are developing such therapies.
