BioPharma, Pharma

In-house CAR-T manufacturing preferable to outsourcing, execs say

Keeping manufacturing close to home allows for greater flexibility, lower long-term costs and building up native manufacturing capability, panelists said at the B. Riley Health Conference Tuesday.

With manufacturing emerging as a hot topic in CAR-T, one question is whether companies should go to outside vendors or do it themselves. At a recent conference, industry executives showed a preference for the latter.

The B. Riley Health Conference took place in New York Tuesday, bringing together executives from several drug companies, as well as academic researchers. One panel discussion, “A Beginner’s Guide to T-Cell Cancer Therapy,” included Mustang Bio CEO Manuel Litchman; Cellular Biomedicine Group CEO Tony Liu; Sorrento Therapeutics president for clinical research, regulatory, drug safety and medical affairs Jerome Zeldis; and Mount Sinai Icahn School of Medicine Professor Miriam Merad, with B. Riley analyst Andrew D’Silva serving as moderator.

With their Food and Drug Administration approval last year and European Medicines Association approval this year, the two marketed CAR-T products – Novartis’ Kymriah (tisagenlecleucel) and Gilead Sciences’ Yescarta (axicabtagene ciloleucel) – now face the test of global, commercial production. In July, Novartis CEO Vasant Narasimhan said in the company’s second quarter earnings call that Kymriah for diffuse large B-cell lymphoma had run into manufacturing problems related to product variability.

In response to a question from D’Silva on whether it was preferable to go with contract manufacturing organizations or manufacture in-house, the executives all said they preferred the in-house option.

For Mustang, analysis showed there were two huge advantages to manufacturing in-house, Litchman said in the panel. While the initial cost is higher than using a CMO, there is quickly a break-even point, and once companies have more than one or two CAR-Ts in development, making the products themselves is the way to go from a cost perspective. The other advantage is flexibility because it allows things to be changed around as clinical data emerge and also eases prioritization, Litchman said. He cited the example of Mustang’s partnership with St. Jude Children’s Research Hospital in Memphis around its gene therapy MB-107, for X-linked severe combined immunodeficiency, for which the company manufacturing its own products was a competitive advantage. Liu added that for his firm, the transition from technology transfer to research and development and then clinical development was made much more efficient through in-house manufacturing.

Moreover, Zeldis said, there is a paucity of CMOs that can do cell culture and gene therapy well. As a result, partnering with them means that companies build up the CMOs’ capacity rather than their own, he added.

One major CAR-T developer that has made significant use of a CMO is bluebird bio, which is partnered with Swiss vendor Lonza for part of the manufacturing of bb2121, its CAR-T that targets the BCMA antigen in multiple myeloma.

Novartis is also using a CMO in Leipzig, Germany, to manufacture Kymriah for the European market, but it plans to open a facility in Paris and is mulling further expansion in Asia; the company has its own plant in New Jersey that it uses for the US. Gilead manufacture products for the US market at a factory it built near Los Angeles International Airport, while for the European market it leased a 117,000-square-foot site near Amsterdam’s Schiphol International Airport. The EMA approved Kymriah and Yescarta near the end of August though they still face reimbursement negotiations with individual countries’ health authorities.

Photo: nopparit, Getty Images

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