SHANGHAI – Although China still has a way to go to approve any CAR T therapy, clinical development is robust with various targets being studied, and the regulatory environment is improving, cell therapy experts said at the Chinatrials 12 Summit.
China is conducting more clinical trials in CAR T therapy than the U.S., according to Hongliang Fang, medical director of Hrain Biotechnology Co. Ltd. In 2017, there were 77 new trials in China, compared to 33 in the U.S. In total, China has 160 clinical trials while the U.S. has 127.
“In 2015, China saw a sharp increase in the number of these trials,” said Fang. “One thing to note is that most of these trials in China are investigator-initiated trials that are not for registration purpose.”
For now, Chinese regulators have approved 16 CAR T products to enter trials. A majority target CD19; BCMA is the second most popular target. They are mostly designed to treat non-Hodgkin lymphoma, acute lymphoblastic leukemia and multiple myelomas. One CAR T candidate targets GPC3 for solid tumors.
In the CAR T competition landscape, Hrain is one of the forerunners, with three products undergoing clinical trials. Another is Nanjing Legend Pharmaceutical & Chemical Co. Ltd., which was the first company to file for an IND. It partnered with Janssen Biotech Inc. to develop LCAR-B38M for relapsed or refractory multiple myelomas.
Another company that receives much attention is Shanghai-based Fosun Kite Biotechnology Co. Ltd., which has advanced its FKC-876 to clinical trials in China. Targeting large B-cell lymphomas, the therapy is already marketed under the brand name Yescarta (axicabtagene ciloleucel) in the U.S. and EU.
Other competitors in the space include Carsgen Therapeutics Ltd., JW Therapeutics (Shanghai) Co. Ltd., Beijing-based Juventas Cell Therapy Ltd., Beijing Immunochina Medical Science and Technology, Cellular Biomedicine Group, Guangzhou Bio-gene Technology Co. Ltd. and Shanghai Unicar-Therapy Biomedicine Technology Co. Ltd.
When comparing CAR T development in China and the U.S., Fang said China is still playing catch-up, but the country is encouraging robust clinical development through improving the regulatory environment.
“We still need to follow the U.S. standards. There’s still a gap between us,” said Fang.
“But we have a few advantages over the U.S. We have a lot of investigator-initiated trials that companies can take over for further development. They involve more new targets, namely CD19, CD20, CD22 and BCMA, for treating lymphoma and leukemia.
“And clinical data from investigator-initiated trials can be used to support an IND submission to waive phase I or even phase II trials,” he added.
Since 2009, the Chinese government has been rolling out regulations on human cell therapy. The most important one, known as the Technical Guiding Principles for Research and Evaluation of Cell Therapy Products, came in 2017. It confirmed that cell therapies will go through regulatory processes in the same manner drugs do.
More detailed regulations have followed to specify how to file for an IND for cell therapies. One advantage that Fang noted was that an institutional ethical and safety review for CAR T clinical trials can be obtained before IND submission, so companies can start clinical trials faster.
But researchers also need to keep in mind the requirements for trial designs. “The NMPA requires clinical trials for CAR T therapies to adopt a 3+3 dose-escalation design and the treatment to be over two weeks. Investigators need to have better time management when designing the clinical trial,” Fang said.
So far, China has yet to approve any CAR T products, but companies that have products under clinical development will eventually have to think about how to enhance their manufacturing capability and commercialize their products.
“CAR T therapy is a complicated product and the risks are high,” said commercialization strategist Howard Chen, principal of management consulting at IQVIA. “Companies need thorough financial planning ahead of time.
“In terms of operation, companies will also need to think about logistics to ensure the safety of the products and education to ensure the product is used correctly. There needs to be training for this process,” he added.
Cellular immunotherapy is a budding area for research in China. According to market intelligence firm Frost & Sullivan, the size of China’s cellular immunotherapy market is expected to increase from ¥1.3 billion (US$181 million) to ¥10.2 billion from 2021 to 2023 at a CAGR of 181.5%.
Frost & Sullivan also predicts that Chinese players will explore more indications for cellular immunotherapy, especially for solid tumors, and the potential of cellular immunotherapy to be used in combination with other therapies. Research into the field is expected to be further diversified.