Kite Submits sBLA to FDA for Yescarta as Second-Line Therapy in Relapsed/Refractory Large B-Cell Lymphoma

October 15, 2021 /BioonBIOON/ -- Gilead Sciences (Gilead)'s cell therapy subsidiary, Kite Pharma, recently announced that it has submitted to the U.S. Food and Drug Administration (FDA) submittedCD19 CAR-T cell therapy Yescarta (Axicabtagene Ciloleucel, Axi-Cel)a supplemental Biologics License Application (sBLA) to expand its current indications:Included adult patients with relapsed or refractory large B-cell lymphoma (LBCL) for second-line treatment. If approved,Yescarta will become the first CAR-T cell therapy for adult patients with LBCL who are relapsed after prior first-line therapy or refractory to first-line therapy.

This sBLA is based on the results of the landmark ZUMA-7 study, which is the first randomized trial to compare CAR-T with standard of care (SOC) in the second-line setting.Clinical Trial, and it is also the trial with the longest follow-up data (2 years) among all Phase III CAR-T trials. The results showed that,In the second-line treatment of relapsed or refractory LBCL, Yescarta demonstrated highly statistically and clinically significant treatment benefits compared with SOC.

Approximately 40% of LBCL patients require second-line therapy due to disease relapse or refractoriness to the treatment regimen. The standard of care for second-line R/R LBCL consists of two steps: reintroduction of immunochemotherapy, and if the patient responds and can tolerate further treatment, proceeding to high-dose chemotherapy andStem CellsTransplantation. The top-line results of the landmark ZUMA-7 study highlight a potential paradigm shift in the treatment of LBCL. The study demonstrated that among patients with LBCL who were relapsed or refractory to first-line chemotherapy, a single infusion of Yescarta significantly improved outcomes compared with conventional long-term second-line standard of care (chemotherapy and consolidative autologous transplantation).

ZUMA-7 is a randomized, open-label, global, multicenter phase 3 study conducted in adult patients with second-line relapsed or refractory large B-cell lymphoma (2nd-line R/R LBCL), comparing Yescarta (single infusion) with standard of care (SOC: chemotherapy +Stem Celltransplantation) were compared. The ZUMA-7 study was initiated in 2017 and enrolled 359 patients across 77 centers worldwide (age range: 22 to 81 years), 30% of whom were aged 65 years or older. The primary endpoint of the study was event-free survival (EFS), defined as the time from randomization to disease progression, initiation of new lymphoma therapy, or death from any cause. The ZUMA-7 study was conducted under a Special Protocol Assessment (SPA) with the U.S. FDA, pursuant to which the trial design, clinical endpoints, and statistical analysis were prospectively agreed upon with theFDAReached an agreement.

The results from the ZUMA-7 trial represent the longest follow-up to date in second-line R/R LBCL, with a median follow-up of 2 years. The results demonstrated that the study met the primary EFS endpoint:Yescarta demonstrated superiority over SOC in the second-line treatment of R/R LBCL, reducing the risk of an EFS event by 60% (HR = 0.398, p < 0.0001),Clinically significant. Furthermore,The study also met the key secondary endpoint of objective response rate (ORR). An interim analysis of overall survival (OS) showed a trend favoring Yescarta., but the current data are not yet mature, and further analysis is planned for the future.

The safety results of this study were consistent with or lower than the known safety profile of Yescarta in third-line treatment of LBCL. Grade 3 or higher cytokine release syndrome (CRS) occurred in 6% of patients, with a median time to onset of 3 days, and grade 3 or higher neurologic events (NE) occurred in 21% of patients. No new safety concerns were identified in the second-line treatment setting.

Yescarta (axicabtagene ciloleucel, axi-cel) is a CD19 CAR-T cell therapy, acquired by Gilead for $11.9 billion through its acquisition of Kite Pharma. In the United States, Yescarta receivedFDAApproved, it is the first CAR-T cell therapy for adult patients with relapsed or refractory large B-cell lymphoma (R/R LBCL).

In March 2021, Yescarta receivedFDAApproval of a new indication: for the treatment of adult patients with relapsed or refractory (R/R) follicular lymphoma (FL) who have received two or more prior lines of systemic therapy. With this latest approval, Yescarta becomes the first CAR T-cell therapy approved for the treatment of FL.

In China, this June, the National Medical Products Administration (NMPA) approved axicabtagene ciloleucel injection (brand name: Yikaida), submitted by Fosun Kite Biotechnology Co., Ltd. (FOSUN Kite), for market launch through the priority review and approval program.. This drug isChina's first approved cell therapy product,For the treatment of adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy (including diffuse large B-cell lymphoma, not otherwise specified, primary mediastinal large B-cell lymphoma, high-grade B-cell lymphoma, and diffuse large B-cell lymphoma transformed from follicular lymphoma).

Axicabtagene Ciloleucel Injection (Yikaida) is based on Kite Pharma’s Yescarta (Axicabtagene Ciloleucel, Axi-Cel) through technology transfer and is intended for localized production in China (excluding Hong Kong, Macau, and Taiwan).. The product was licensed by Fosun Kite from Kite Pharma, granting Fosun Kite the technology and commercialization rights in Mainland China, the Hong Kong Special Administrative Region, and the Macao Special Administrative Region.

This product is the first CAR-T cell therapy product commercialized by Fosun Kite in China, and also the first CAR-T cell therapy product officially approved for marketing by the National Medical Products Administration (NMPA). As a novelTumorAs a treatment option, axicabtagene ciloleucel injection (Yescarta) can bring new hope and opportunities for a new life to Chinese patients with relapsed or refractory large B-cell lymphoma who have received two or more lines of systemic therapy. (Bioon.com)

Original Source:Kite Submits Supplemental Biologics License Application to U.S. Food and Drug Administration for Earlier Use of Yescarta in Large B-cell Lymphoma