- Novartis and Gilead Sciences separately announced Monday that the European Commission had approved their respective CAR-T therapies, Kymriah and Yescarta.
- Kymriah is now cleared for European patients younger than 25 years old with B-cell acute lymphoblastic leukemia that is either refractory, has relapsed after a transplant or has relapsed at least twice overall. It's also OK'd as a third-line therapy for adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).
- Yescarta received the same DLBCL approval, as well as one for primary mediastinal large B-cell lymphoma after two or more lines of systemic therapy. The regulatory wins should boost sales for both Kymriah and Yescarta, though they'll also create greater manufacturing demands for their parent companies.
Patients eligible for CAR-T therapies are extremely sick and in need of quick treatment. In their attempts to meet that need, Gilead and Novartis are extracting, engineering and reinfusing CAR-T cell therapies in about two and a half to three weeks.
That's still a fast turnaround, requiring substantial investment in manufacturing capabilities and supply chain logistics. And as the approval footprints for Yescarta (axicabtagene ciloleucel) and Kymriah (tisagenlecleucel) grow, so too do the production challenges.
Earlier this year, Gilead disclosed it had leased a facility near the Schiphol airport in Amsterdam to support Yescarta manufacturing. The biotech expects the nearly 120,000-square-foot site to be fully operational by 2020.
That's around the same time Novartis anticipates European patients will begin receiving the first shipments of Kymriah from the company's manufacturing plant in Stein, Switzerland. The big pharma plans to inject 90 million Swiss francs ($92 million) into the plant in a staggered fashion over the next three years, possibly creating up to 450 new jobs in the process, according to a company spokesperson.
"Novartis is already working to establish a network of select treatment centers that will offer Kymriah in the EU," the spokesperson wrote in an emailed statement to BioPharma Dive, adding "the centers are required to undergo training to adhere to quality standards for cell supply and manufacturing in order to ensure patient safety. At this time, we cannot comment on which countries will have the first treatment centers qualified."
Ensuring manufacturing quality and capacity is vital for all drug classes, yet it's especially necessary for personalized medicines like CAR-T therapies where supply chain delays or mix-ups can have dire consequences. It's a burden even big pharmas are having trouble with — exemplified by Novartis, which discussed on its most recent quarterly earnings call some difficulties it was having in making Kymriah for adult lymphoma patients.
Perhaps to that end, second quarter Kymriah sales were lower than some analysts had predicted. They totaled $16 million, slightly up from the $12 million the therapy fetched in the previous quarter but still significantly behind the $68 million posted by Yescarta.
Novartis is looking to avoid such setbacks as it rolls out Kymriah in Europe. It already has deals in place with French contract manufacturer Cell for Cure, Germany's Fraunhofer Institute, and a Japanese contract manufacturing and development organization.
The company spokesperson noted that Kymriah's European launch will initially be aimed at the B-cell acute lymphoblastic leukemia indication, while the launch in DLBCL will happen "progressively, in line with managing recently identified variability in meeting commercial product specifications for DLBCL."