The market for cell therapy products such as CAR-T is expected to expand rapidly based on increasing investment from the industry and the implementation of advanced technologies.
Chimeric antigen receptor (CAR) T-cell therapy is a novel and effective therapeutic approach that has emerged to revolutionize cancer treatment, especially for blood cancers. This therapy achieves a therapeutic effect or heals disease through repairing or reconstructing damaged genetic materials. Since Roseberg isolated tumour-infiltrating lymphocytes (TILs) in 1986 to treat melanoma for the first time , modified T cell therapy has been gaining great momentum for the development. After the first CAR-T therapy Kymriah was approved by FDA in 2017, CAR-T market has witnessed rapid growth. According to Frost & Sullivan, the global CAR-T market size is expected to grow from USD 10 million in 2017 to USD 1.08 billion in 2020, then reach USD 9.05 billion in 2025 with a compound annual growth rate (CAGR) of 55% from 2019 to 2025, which makes it the fastest growing sector in the global cell and gene therapies (CGT) market.
CAR-T therapy is one of the subsegments in CGT therapy. Based on the origin of T cells, CAR-T therapy can be classified into two types. Autologous CAR T-cell therapy that uses patient’s own immune cells, and allogeneic CAR T-cell therapy that uses T cells from donor blood or sometimes umbilical cord blood. Most CAR-T therapies belong to autologous CAR T-cell therapies, which typically involves the following steps: 1) T cells are first harvested from patient’s peripheral blood cells; 2) viral vectors such as AAV then modify T cells with CAR genes that are directed against a specific cell-surface protein on cancer cells; 3) then the modified CAR-T cells population is expanded according to the patient’s weight; 4) finally the expanded CAR-T cells are reinfused back into the patient. The whole manufacturing process lasts for one to three weeks and requires the compliance with GMP practice under ultra clean environment.
To date, CAR-T therapy has achieved unprecedented efficacy in the treatment of chemotherapy-resistant or refractory B-cell malignancies such as R/R, B-ALL, NHL, and MM. The effectiveness in solid tumors is now also being investigated. For all the CAR-T therapies, CD19-targeting and BCMA-targeting CAR-T therapy achieve greater clinical success. Among six FDA-approved CAR-T therapies, four therapies choose CD19 target and two choose BCMA target.
Compared to small and large molecule drugs, the most prominent advantage is that patients can replace lifelong treatment of chronic disease with the administration of a limited number of doses or even just one. Dr. Zheng, the CEO of BRL Biotech (Chinese: 邦耀生物), explains to EqualOcean: "CAR-T therapy is a backbone therapy in blood cancer and is potentially a sing-dose curative gene therapy".
US is the pioneer that led the development of CAR-T industry. But in the mid-2010s, China learned fast and has been chasing up with US. The key drivers can be mainly ascribed to Chinese government’s support to build a CGT ecosystem that includes biotech companies, academics, healthcare providers, investors, and the government. After biotechnology was prioritized in the 13th Five-Year Plan, Chinese government explicitly emphasized its strategy to accelerate the pace of innovation and development of biotech industries, including cell therapy. Relevant ministries have also issued encouraging acting regulations.
The capital market also became active after the publication of Opinions of the State Council on Reform of the System of Evaluation, Review and Approval of Drugs and Medical Devices in 2015. From 2018 to 2021, Chinese cell-therapy companies have raised approximately USD 2.4 billion in funding, growing at a compound annual growth rate of 45%.
Under this energetic ecosystem, by 2018, the number of CAR-T therapy trials in China had surpassed those in US. As of June 2022, 342 clinical CAR-T trials have been conducted by Chinese companies. B-lineage malignancies were among the most frequent indications. Among many drug candidates, two CAR-T products have gained commercial application, Yescarta approved in June 2021 and Relma-cel approved in September 2021.
The domestic CAR-T market size is expected to grow from CNY 0.2 billion in 2021 to 8 billion in 2025, and reach 28.9 billion in 2030 with a CAGR of 45% from 2022 to 2030, according to Frost & Sullivan. Although Chinese CAR-T market is still in its infancy stage, strong driving force exists.
Although the two approved CAR-T products are from Sino-US JVs Fosun Kite (Chinese: 复星凯特) and JW Terapeutics (Chinese: 药明巨诺), domestic players have also made breakthroughs these years and caught up with global players. Legend Biotech (Chinese: 传奇生物), IASO Biotherapeutics (Chinese: 驯鹿生物), and CARsgen Therapeutics (Chinese: 科济药业) all receive NDA acceptance of their BCMA CAR-T products, making them the first tier company in BCMA CAR-T therapy. Juventas Therapeutics (合源生物), Gracell Biotechnologies (Chinese: 亘喜生物), Hrain Biotechnology (Chinese: 恒润达生), ImunoPharm (Chinese: 艺妙神州), Shanghai Cell Therapy Group (Chinese: 上海细胞治疗集团) and many domestic companies put efforts in CD19 CAR-T products. Juventas Therapeutics (Chinese: 合源生物) is the leader as NMPA accepted its NDA of CNCT19, which means a milestone in Chinese CD19 CAR-T therapy. CARsgen Therapeutics (Chinese: 科济药业) is a global leader in solid tumors and its CT041 is the world's first CAR-T candidate for the treatment of solid tumors entering Phase II clinical trial. Bioheng Biotech (Chinese: 北恒生物) and BRL Biotech (Chinese: 邦耀生物) develop new markets in allogeneic CAR-T.
Fosun Kite (Chinese: 复星凯特) is a joint venture between Fosun Pharmaceutical and Kite Pharma founded in 2017, focusing on the advancement and commercialization of innovative immune cell therapy. In June 2021, Fosun Kite's Axicabtagene Ciloleucel for the treatment of R/R LBCL gained the first CAR-T therapy approval in China. Axicabtagene Ciloleucel is an autologous CD19 CAR-T therapy manufactured in China pursuant to a license from Kite's Yescarta (axicabtagene ciloleucel), which is the world's first approved CAR-T therapy for adult patients with certain types of NHL.
JW Therapeutics (Chinese: 药明巨诺) is a Hong Kong listed joint venture between BMS’ Juno Therapeutics and WuXi AppTec founded in 2016, focusing on the development and commercialization of cell immunotherapy products. In September 2021, NMPA approved its autologous CD19 CAR-T therapy relmacabtagene autoleucel (relma-cel) to treat large B-cell lymphoma, making it the second approved CAR-T product and the first approved as Category 1 biologics product in China. In October 2022, NMPA approved its second indication and makes it the first cell immunotherapy product in China for the treatment of R/R FL patients.
Legend Biotech (Chinese: 传奇生物) is a global, commercial-stage biotechnology company listed on NASDAQ with seven clinical-stage products. It is the first Chinese company to achieve the overseas commercialization of self-developed CAR-T products. Its lead product candidate Cilta-Cel was the first Chinese CAR-T therapy to be approved by FDA in February 2022. Then the European Commission and Japan’s Ministry of Health, Labour and Welfare granted conditional marketing authorization of Cilta-Cel. In January 2023, NMPA formally accepted its NDA for Cilta-Cel. Cilta-Cel's successful commercialization in global markets is regarded as a milestone in Chinese innovative drug industry.
CARsgen Therapeutics (Chinese: 科济药业) is a clinical-stage company focusing on innovative CAR T therapies for the treatment of hematologic malignancies and is a leader in solid tumors. Now the company has four clinical-stage products. CT053 is an autologous BCMA CAR-T candidate for the treatment of R/R MM and received RMAT and Orphan Drug designations from FDA in 2019. In October 2022, NMPA accepted the NDA for CT053, making it the second BCMA-targeting therapy in China to receive the application. CT041 is another star candidate against the protein Claudin18.2 and has the potential to be first-in-class globally. CARsgen was the first in the world to successfully identify, validate and report CLDN18.2 as a solid tumor-associated antigen and conducted a Phase II clinical trial for the treatment of solid tumors.
Juventas Therapeutics (Chinese: 合源生物) is a biopharmaceutical company founded in 2018 focusing on developing and commercializing innovative therapeutics and pharmaceutical products. Now it has more than 10 product candidates represented by innovative single/multiple target products, universal cell therapy products. In December 2022, NMPA accepted the NDA for company's CNCT19 (Inaticabtagene Autoleucel) for the treatment of adult patients with R/R ALL, which was the first CAR-T therapy for the treatment of B-ALL and had the potential to be the first approved domestically developed CD19 CAR-T therapy in China. It has also been granted the Orphan Drug Designation from the FDA.
Bioheng Biotech (Chinese: 北恒生物) is a leading biomedical company specialized in the development and commercialization of allogeneic cellular immunotherapy. Founded in 2017, to date Bioheng has raised approximately CNY 620 million in Series A and Series B within 4 years. In March 2022, CDE approved the first Universal CAR-T drug Bioheng's CTA101. CTA101 is independently developed by Bioheng targeting CD19 and CD22, for the indication of adult R/R B-ALL.