Clinical outcomes are one of the gold standards for assessing the availability of new drugs, which often determines their reputation after listing. As a “living drug”, CAR-T therapy is to collect blood from patients, transport blood samples to the production GMP center, extract and purify T cells, lentivirus transfection and cell expansion, final formulation production and quality, and finally return to the hospital to return to the patient.
Novartis’s Kymriah (tisagenlecleucel) and Gilead’s Yescarta (axicabtagene ciloleucel) are facing global commercial production after being approved by the FDA and the European Union.
In July of this year, Novartis CEO Vas Narasimhan said, “While Kymriah has expanded from the treatment of diffuse large B-cell lymphoma to other indications, it still needs to continuously optimize the CAR-T process, and continuously research in CMC. Innovation.”
Switzerland’s “New Zurich News” reported on August 27 that the anti-cancer drug Kymriah developed by the Swiss Novartis Group can only be commissioned by other companies due to production capacity restrictions. Novartis has announced that it will spend three years expanding its production line in Stein, Aargau, northern Switzerland, to increase production of Kymriah to ensure market demand.
Since CMC is a key component in the preparation of CAR-T cells, it is necessary to find an external supplier (CDMO) to solve the problem that the company has to consider. At a recent seminar on “The Beginner’s Guide to T Cell Cancer Therapy”, industry executives showed a preference for the latter.
Manuel Litchman, CEO of Mustang Bio, showed that there are two major advantages to internal manufacturing. On the one hand, although the initial cost is higher than the use of CMO, there will soon be a break-even point, especially when the company has multiple CAR-T products developed, the cost-effectiveness will be significantly improved; on the other hand, he believes that internal manufacturing More flexibility, such as their company’s X-linked severe combined immunodeficiency drug candidate, can be improved according to the clinical trial results.
Tony Liu, CEO of Cellular Biomedicine Group, added that from the perspective of his company’s operating experience, whether it is technology transfer or pre-clinical research and development transition to clinical registration development, the self-controlled internal manufacturing is obviously more efficient.
Jerome Zeldis, president of clinical research supervision, drug safety and medical affairs at another CAR-T company, Sorrento Therapeutics, said that there is currently no CDMO available on the market for cell culture and gene therapy product development. The ability to build the latter in the opposite direction, rather than improving their own level.
However, there are also CAR-T developers who have chosen CDMO companies, such as bluebird bio, which works with Swiss supplier Lonza to produce bb2121, a drug that targets BCMA antigens for the treatment of multiple myeloma.
EMA approved Kymriah and Yescarta at the end of August. Novartis is currently using a CDMO from Leipzig, Germany to produce Kymriah for the European market, but it plans to open a factory in Paris and is considering further expansion in Asia; the products currently supplied to the US are It is produced at its own New Jersey facility. Gilead also adopted the principle of building its own factory. There are already factories near Los Angeles International Airport, and a 117,000-square-foot site has been leased near Amsterdam Airport Schiphol for the European market.
It is not difficult to see that although Novartis and Gilead’s products still face reimbursement negotiations with national health authorities, they even advocate self-built factories.