Novartis constructing $92m CAR-T plant as Kymriah arrives in EU

Up to 450 jobs will be created as Novartis commits to a production site for cell and gene therapies in Switzerland. The investment will support CAR-T drug Kymriah, which received European approval this week.

A year after the US Food and Drug Admistration (FDA) approved Kymriah (tisagenlecleucel), the European Commission (EC) has granted the Novartis’ therapy approval to treat B-cell acute lymphoblastic leukemia (ALL).

The Stein facility will be located about 100km east of Novartis’ headquarters in Basel, Switzerland. Image: iStock/Denis Linine.

The Stein facility will be located about 100km east of Novartis’ headquarters in Basel, Switzerland. Image: iStock/Denis Linine.”

In the US, the chimeric antigen receptor T cell (CAR-T) product is manufactured at Novartis’ Morris Plain, New Jersey facility. In Europe, the firm has prepared for approval through several manufacturing initiatives both in-house and out.

The manufacture of complex, autologous individualized cellular therapies poses specific challenges with regards to capacity planning, and as such specifics with regards to volume have not been divulged, a spokesperson told BioProcess Insider.

“As this innovative treatment approach is made available to more patients globally, Novartis has been actively pursuing options for additional manufacturing facilities beyond our Morris Plains facility in New Jersey,” we were told.

Swiss manufacturing

This includes plans for a new cell and gene therapy production facility in Stein, Switzerland, unveiled by Novartis this week.

The plant for innovative cell and gene therapies “will drive forward the adoption of breakthrough cell-based therapies in Europe,” the firm told us. “The manufacturing site will include manufacturing for commercial and clinical trial product, and will help to offer additional manufacturing capacity in Europe for Kymriah.”

Phased investments totalling approximately CHF 90 million [US$92 million] will be made over the next few years to support the new facility.

“Initially, around 260 new positions will be created with a potential of 450 new jobs over the next three years. The first delivery out of Stein to patients in Europe is expected by early 2020.”

CDMO use

The investment comes in addition to a recent deal with French contract development and manufacturing organization (CDMOs) CELLforCURE, inked in July.

“The agreement with CELLforCURE includes manufacturing commercial and clinical products and helps to offer additional manufacturing capacity in Europe,” Novartis said. “Technology transfer involves a gradual process; production could start in 2019 following transfer of our innovative manufacturing technology to CELLforCURE.”

Anticipated CELLforCURE capacity has not been divulged, due to proprietary reasons.

Novartis also has manufacturing capacity at the Fraunhofer-Institut for cell therapy and immunology (Fraunhofer-Institut für Zelltherapie und Immunologie) facility in Leipzig, Germany.

“Novartis has successfully transferred the Kymriah manufacturing process at the Fraunhofer-Institut for cell therapy and immunology… and has expanded their alliance to support the manufacturing of Kymriah for clinical trials and for post approval manufacturing, including in support of certain agreed compassionate use programs.”

Asia and beyond

Novartis also has one eye on the Asian market, having procured the services of a CDMO in Japan. Technology transfer efforts to the firm have begun, the firm confirmed but further details – including the name of the CDMO – have not been divulged.

Last month, Novartis reported some issues in the manufacturing of Kymriah around the variability in its product specifications. “This is something we’re looking at now in DLBCL to make sure that we can continue to ramp-up the demand,” CEO Vasant Narasimhan said on a conference call.

In related news, the EC has also approved Gilead/Kite’s CAR-T therapy Yescarta (axicabtagene ciloleucel) for the treatment of patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) and primary mediastinal large B-cell lymphoma (PMBCL).