Kite, Juno ramping up commercial manufacturing capacity for CAR-T

Next-generation T-cell cancer therapies have recently shown tremendous promise, with some small cancer trials demonstrating remission rates of 80% and higher. Biotechs like Kite and Juno have garnered substantial interest on the promise of these therapies, typically known as CAR-T. Both companies plan to back that up with significant spending plans as they compete to beat each other to FDA approval and market. 

But, as they ramp up, manufacturing challenges and the responses each company takes will become more important. The unique problems of engineering T-cells for the cancer therapies amplifies the need for responsive manufacturing.

Challenges of CAR-T manufacturing

CAR-T therapies, or chimeric antigen receptor T-cells, work by extracting the immune system T-cells from a patient and genetically modifying them to seek out and destroy cancer cells. The T-cells are altered by adding antigen receptors, and then reintroduced into the patient.

Both Kite and Juno, along with their big pharma competitor Novartis, have taken an “autologous” approach to CAR-T, taking T-cells from each individual patient. But, because of this intensive process, the production process is both lengthy and individualized. Furthermore, the re-engineered cells have to be durable enough to be reintroduced to the human body.

Other companies, like the French firm Cellectis, are attempting an “allogenic” approach, which uses unmatched T-cells for universal treatment rather than individual by individual. This, however, runs the risk of graft-host rejection.

Kite versus Juno

Both Kite and Juno are aiming to generate data from their initial clinical trials by late 2016, and are targeting a 2017 US approval, according to a report from EP Vantage. Kite hopes its Zuma-1 lymphoma trial will yield interim results by the second half of the year, while Juno is expecting data from its Rocket study in late 2016.

Kite’s has four multi-center clinical studies ongoing for its CAR-T therapy, KTE-C19, studying its effect against large B cell lymphoma, relapsed mantle cell lymphoma, and acute lymphoblastic leukemia (ALL). It leases two plants, one of which will be used for the manufacturing of T-cells in clinical studies. The other is on track for qualification and validation for commercial production later this year, according to Kite’s fourth quarter earnings report.

Juno, on the other hand, aims to initiate operations at a leased plant in Bothell, Washington at the end of this quarter, writes EP Vantage. The Rocket study is for the treatment of adult ALL.

(Note: Neither company has received FDA approval for its therapies.. In reveiwing a drug for regulatory approval, the FDA will also inspect the manufacturing facilities and processes associated with the drug.)

Big pharma competition

The two companies will also be eyeing Novartis, which expects to file its CAR-T product CTL019 sometime in 2017. While its timeline has slipped, Novartis is already producing CAR-T cells for clinical use at a plant it owns in New Jersey.

According to Reuters, Novartis may have a manufacturing advantage over Kite and Juno with its larger footprint and experience in pharma manufacturing.

Key here will be cost. Intensive, individualized manufacturing processes for the CAR-T therapies will push prices up, potentially into the hundreds of thousands of dollars.

If Kite, Juno, or Novartis can push down the engineering time to modify the T-cells, they could become more competitive on price. However, in a therapy area fraught with risks, safety will remain paramount.

In addition to driving up costs, the individualized process for autologous CAR-T therapies limits uptake. This means costs have to be spread over fewer potential patients, at least initially.

As the EP Vantage report points out, the focus on getting commercial manufacturing processes up and running will burn a substantial amount of cash. Both Kite and Juno have bulked up on cash to meet future demands.

Kite had $614 million in cash and cash equivalents at the end of Q4, up from roughly $370 million a year early. Juno, on the other hand, is sitting on $940 million, more than double its cash at the end of 2014. Both companies generated an annual net loss last year. 

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Filed Under: Manufacturing