HONG KONG – Cellular Biomedicine Group Inc. has inked a partnership with Novartis AG to bring Kymriah (tisagenlecleucel) to market in China, putting it in a race with competing CAR T-cell therapy Yescarta (axicabtagene ciloleucel, Gilead Sciences Inc.), which is expected to soon start clinical trials in the country. (See BioWorld, Sept. 13, 2018.)
Both are the only approved CD19-directed CAR T-cell therapies on the market, currently approved in the U.S., EU and Canada. In August 2017, Kymriah was approved by the FDA to treat relapsed or refractory acute B-cell precursor acute lymphoblastic leukemia (ALL) in patients aged 25 or below. In May, it obtained the second FDA approval for treating diffuse large B-cell lymphoma (DLBCL) – the most common form of non-Hodgkin's lymphoma (NHL) – as well as high grade B-cell lymphoma and DLBCL arising from follicular lymphoma. It got green lights in the EU and Canada in August and September, respectively.
But China's approval is so far nowhere to be seen. "China is where the number of patients in need remains the highest in the world," said Tony Liu, CEO of CBMG.
In China, the number of new annual NHL patients is said to reach 73,000, with DLBCL making up the largest proportion.
Under the terms of its Novartis deal, CBMG will manufacture and supply Kymriah, while the Swiss pharma will handle the distribution, registration and commercialization of the leukemia therapy and hold the marketing license. CBMG will receive $40 million from Novartis through selling about 1.5 million shares – around a 9 percent stake – at $27.43 per share. The Chinese firm will also get a single-digit escalating percentage collaboration payment based on net sales of Kymriah and a markup on the manufacturing cost.
"This agreement provides for certain technical transfer services from Novartis to CBMG, while at the same time, CBMG will transfer certain royalty-free worldwide intellectual property rights to Novartis," Liu told BioWorld Asia.
After the $40 million initial investment, the "next step is to work out the technology transfer and align our Shanghai GMP facility with Novartis' requirements to bring Kymriah to patients in China," said Liu.
"CBMG currently has ample production capacity to support Kymriah," he added. In November 2017, the company opened a 100,000-square-foot facility in Shanghai for CAR T clinical studies.
Pascal Touchon, senior vice president and global head of Cell & Gene at Novartis Oncology, said the collaboration could expand that company's Kymriah manufacturing capabilities.
The target turnaround time for manufacturing Kymriah in China is not immediately known. In the U.S., it is 22 days.
Yescarta ahead so far
Meanwhile, Kymriah's competitor, Yescarta, is ahead. On Sept. 6, Shanghai-based Fosun Kite Biotechnology Co. Ltd, received approval to start clinical trials, taking advantage of recent efforts by Chinese regulators to streamline the drug development and approval process.
Richard Wang, CEO of Fosun Kite, told BioWorld Asia the approval arrived in less than 70 working days, earlier than other CAR T-cell therapies.
Fosun Kite, a joint venture set up by Shanghai Fosun Pharmaceutical Ltd. and California-based Kite Pharma Inc. (now part of Gilead Sciences), has the rights to develop, manufacture and market it in the Chinese mainland and the Hong Kong and Macau special administrative regions.
CBMG and Fosun Kite are not the only Chinese biopharma firms developing CAR T therapy for blood cancers.
In March, Nanjing Legend Pharmaceutical & Chemical Co. Ltd. became the first Chinese drugmaker to be approved to push its CAR T-cell therapy, LCAR-B38M, into clinical trials. The company entered a $350 million deal with Janssen Biotech Inc. to develop LCAR-B38M to treat relapsed or refractory multiple myeloma in December 2017.
Six other Chinese cell therapy developers are awaiting approvals for their clinical trial applications, including Beijing Immunochina Pharmaceuticals Co. Ltd., Guangzhou Bio-gene Technology Co. Ltd, Pregene (Shenzhen) Biotechnology Co. Ltd., Hrain Biotechnology Co. Ltd., Carsgen Therapeutics Ltd. and Shenzhen Innovation Immunotechnology Co. Ltd.
Their applications were accepted by the Chinese regulators between February and July this year.
Such competition is encouraged by the Chinese regulators recently giving clearer guidance regarding cell therapies. In December, China published technical guidelines on research and evaluation of cellular therapies products. Three months later, it issued guidance on the pharmaceutical research in clinical trials and submission of application documentation.
Both documents provide the framework for the development of cell therapies, including the clinical trial application procedure.
As one of the players in the space, CBMG focuses on immunotherapies for cancer and stem cell therapies for degenerative diseases, based on technologies developed both in-house and obtained from partners.
"Our current priority is to collaborate with Novartis to bring Kymriah to China," said Liu. "At the same time, we remain committed to developing our existing pipeline of immunotherapy candidates for hematologic and solid tumor cancers to meet the unmet demand."
Liu said China has four times as many cancer patients as the U.S. and there are about 4.3 million new cancer patients annually.
"Our oncology pipeline includes preclinical compounds targeting CD20-, CD22- and B-cell maturation antigen-specific CAR T compounds, and T-cell receptor and tumor-infiltrating lymphocyte technologies," said Liu.
Its anti-CD19 CAR T therapy, C-CAR011, for treating ALL has been pending IND approval in China since April.