FDA Greenlights Gilead/Kite’s Tecartus for Mantle Cell Lymphoma

Green signal to Tecartus 

The U.S. Food and Drug Administration (FDA) approved Kite Pharma’s Tecartus (brexucabtagene autoleucel) for adults with relapsed or refractory mantle cell lymphoma (MCL). Kite is a Gilead Science company.

Tecartus is the first and only approved chimeric antigen receptor (CAR) T-cell therapy for this indication. It was approved under Priority Review and also had the FDA’s Breakthrough Therapy Designation.

The approval was built on the results of ZUMA-2, a single-arm, open-label trial. In it, 87% of patients responded to a single infusion of the drug. Of them, 62% had a complete response (CR). The drug is approved with a Boxed Warning over the risk of cytokine release syndrome (CRS) and neurologic toxicities, a risk found with CAR-T and other immuno-therapies. As such, the company is required to have a Risk Evaluation and Mitigation Strategy (REMS), which is used to educate healthcare professionals on the therapy’s risks and provide training and certification.

“Despite promising advances, there are still major gaps in treatment for patients with MCL who progress following initial therapy,” said Michael Wang, ZUMA-2 Lead Investigator and professor, Department of Lymphoma and Myeloma, Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center.

Wang added, “Many patients have high-risk disease and are more likely to keep progressing, even after subsequent treatments. 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% and early clinical evidence suggesting durable remissions in later lines of therapy.”

Gilead Sciences completed the acquisition of Kite Pharma in October 2017, which it bought for about $11.9 billion. One of the big reasons for the acquisition was Kite’s Yescarta (axicatagene ciloleucel), which was approved by the FDA in the same month. Yescarta, also a CAR-T therapy, was approved for relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (CLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma (PMBCL), high-grade B-cell lymphoma, and DLBCL arising from follicular lymphoma (transformed follicular lymphoma, or TFL).

It was approved only shortly after the first CAR-T product, Novartis’ Kymriah (tisagenlecleucel) for acute lymphoblastic leukemia.

In CAR-T therapies, a patient’s T-cells are collected, shipped to a manufacturing site, engineered to attack the patient’s unique cancer cells, and delivered back to the patient’s physician, who infuses the treatment back into the patient. This becomes something of a “living therapy.” But for certain indications, it can be very effective.

And expensive. In the U.S., Yescarta has a list price of about $373,000. Kymriah has a price tag of about $475,000.

Tescartus uses a different technology than Yescarta. Tecartus requires T-cell selection and lymphocyte enrichment, which according to Ken Takeshita, Kite’s global head of clinical development, is “necessary in B-cell malignancies such as mantle cell in which there are circulating lymphoblasts in the peripheral blood. The manufacturing method was tailored to this particular type of lymphoma.”

One possible market advantage for Tecartus is that for this indication, patients will not necessarily require to have been treated by a BTK inhibitor, such as Johnson & Johnson and AbbVie’s Imbruvica.

MCL is a rare form of non-Hodgkin lymphoma (NHL) that originates from cells in the “mantle zone” of the lymph node. It mostly affects men over the age of 60. It is very aggressive after relapse.

“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,” said Meghan Gutierrez, chief executive officer of the Lymphoma Research Foundation. “In the past decade, researchers have made significant progress in our understanding of this disease and 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. Today’s news builds upon this progress and provides hope to mantle cell patients and their loved ones.”