The U.S. Food and Drug Administration (FDA) has granted accelerated approval to Kite Pharma’s CAR T-cell therapy Tecartus (brexucabtagene autoleucel) for adults with relapsed or refractory mantle cell lymphoma (MCL).
The decision comes less than six months after the FDA accepted to analyze, under priority review status, Kite’s biologics license application, shortening review time from the standard 10 months to six months. The therapy also previously received the FDA’s breakthrough therapy status for the same indication.
Tecartus will be used to treat people with a typically aggressive, rare form of non-Hodgkin lymphoma.
A similar application is being reviewed in the EU by the European Medicines Agency, which also granted a priority medicines designation to Tecartus.
“This approval marks the first CAR T cell therapy approved for mantle cell lymphoma patients and represents a new frontier in the treatment of this disease,” Meghan Gutierrez, CEO of the Lymphoma Research Foundation (LRF), said in a press release.
Formerly known as KTE-X19, and developed by Gilead Sciences-owned Kite, Tecartus is a type of immunotherapy that uses a person’s own modified T-cells — a type of immune cell — to fight cancer. The patient’s T-cells are collected and then modified in the lab, after which they are expanded and infused back into the individual.
Specifically, Tecartus contains T-cells modified to produce a chimeric antigen receptor or CAR, a man-made receptor that helps immune cells recognize a certain cancer protein called CD19.
It shares the same design as the company’s first approved CAR T-cell therapy, Yescarta (axicabtagene ciloleucel), used to treat adults with large B-cell non-Hodgkin lymphoma. However, Tecartus has an additional manufacturing step in which circulating tumor cells are separated from immune cells. This step, called white blood cell enrichment, is necessary for certain types of B-cell blood cancers, including MCL.
“Kite is committed to bringing the promise of CAR T therapy to patients with [blood] cancers, and as such, we are proud to launch our second cell therapy,” said Christi Shaw, Kite’s CEO.
“We look forward to partnering with the lymphoma community to deliver this potentially transformative therapy to patients with relapsed or refractory MCL,” Shaw added. Of note, refractory cancers are ones that do not respond to treatment.
The FDA’s approval was based on data from the ZUMA-2 Phase 2 trial (NCT02601313), which enrolled 105 people with MCL who had received up to five prior therapies, including a chemotherapy, an anti-CD20 antibody, and a Bruton’s tyrosine kinase inhibitor (BTKi).
The open-label study showed that a single dose of Tecartus significantly reduced tumor burden in 87% of adults with relapsed or refractory MCL, including a complete cancer eradication in 62% of participants.
These response rates were largely superior to those typically seen in people with MCL who progress on BTKi therapies, according to a Targeted Oncology’s news release. Those rates usually are between 25% and 42%, the release noted.
Previous results showed that one year after treatment, 83% of the first 28 participants were still alive, with 61% of them having shown no signs of disease progression.
Tecartus also showed a generally manageable safety profile. Severe or life-threatening adverse events included neurologic toxicity (37%) and cytokine release syndrome or CRS (18%), a serious inflammatory response triggered by the therapy.
Based on these safety concerns, Tecartus’ prescribing information includes a warning for the risk of CRS and neurologic toxicities.
The therapy is only available through a risk evaluation and mitigation strategy (REMS), which ensures that the benefits of Tecartus outweigh the risk of these side effects. Tecartus REMS has been combined with Yescarta’s REMS and is now called the Yescarta and Tecartus REMS program.
To be able to use Tecartus, treatment centers must be specially certified by the FDA and have properly trained staff to recognize and manage severe side effects.
“The availability of Tecartus as the first-ever cell therapy for patients with relapsed/refractory MCL provides an important option with a response rate of nearly 90 percent and early clinical evidence suggesting durable remissions in later lines of therapy,” said Michael Wang, MD, ZUMA-2’s lead investigator and a professor at the University of Texas MD Anderson Cancer Center.
The LRF’s Gutierrez noted that researchers have made significant progress in the last decade in increasing understanding of the disease.
“We have seen an increase in clinical trials for patients, which we hope will continue to improve treatment strategies and the options available to people with mantle cell lymphoma,” Gutierrez said. “Today’s news builds upon this progress and provides hope to mantle cell patients and their loved ones.”
Tecartus will be included in Kite’s integrated technology platform, called Kite Konnect. That platform provides assistance and information on the manufacturing, shipment, insurance benefits, and travel support available to eligible patients receiving Yescarta and Tecartus and to their healthcare teams.
The therapy also is being evaluated in Phase 1/2 trials as a potential treatment for people with acute lymphoblastic leukemia and chronic lymphocytic leukemia.
