U.S. FDA Approves Label Update for Yescarta® Including Prophylactic Corticosteroid Use to Improve CRS Management

News on February 11, 2022 /BioValleyBIOON/ -- Gilead Sciences' cell therapy company, Kite Pharma, recently announced that the U.S. Food and Drug Administration (FDA) has approved the updated prescribing information for the CD19 CAR-T cell therapy Yescarta (Axicabtagene Ciloleucel, Axi-Cel):Inclusion of prophylactic use of corticosteroids in all approved indicationsIt is worth mentioning that,Yescarta is now the first and only CAR-T cell therapy with information included in the label to help physicians manage and potentially provide preventive treatment for side effects.。Updated toxicity management strategies can improve certain adverse events without affecting the activity of Yescarta.。

This label update is based on the results of a new safety management cohort (Cohort 6) from the pivotal ZUMA-1 study, which aims to evaluate the impact of prophylactic use of corticosteroids, early use of corticosteroids and/or tocilizumab (anti-IL-6R antibody), and prophylactic use of levetiracetam on the incidence and severity of cytokine release syndrome (CRS) and neurologic events (NE).

The ZUMA-1 study also included Cohort 4, which was added in May 2021.FDATags. Column 4 evaluated the early treatment with corticosteroids and/or tocilizumab and prophylactic levetiracetam. Cohort 6 was built on the growing knowledge gained over the years in developing Yescarta regarding how to manage and minimize side effects. Cohort 6 evaluated 39 patients with relapsed or refractory LBCL. Before Yescarta infusion, patients began receiving oral dexamethasone 10 mg once daily for three consecutive days. Compared with the pivotal cohorts (Cohorts 1 and 2) of the ZUMA-1 study, the initiation time of corticosteroids and tocilizumab was earlier in Cohort 6, and the levels of CRS and neurologic events were lower. All 39 patients received three doses of prophylactic corticosteroids.

In Cohort 6, no ≥Grade 3 CRS events occurred (0%, 0/39), compared to an incidence of 13% (14/108) in the pivotal Cohorts 1/2. In Cohort 6, 13% of patients experienced ≥Grade 3 neurologic events (13%, 5/39) as of the data cutoff, with one patient experiencing a late-onset Grade 5 event after the data cutoff; whereas the incidence in the pivotal Cohorts 1/2 was 31% (33/108).In addition, Cohort 6 showed that in patients experiencing CRS and neurologic events, the median time to onset of CRS was 5 days (range, 1-15 days) and the median time to onset of neurotoxicity was 6 days (range, 1-274 days).

Other recently released data show that 68% (27/40) of patientsNo CRS or neurologic events were reported within 72 hours after Yescarta infusion.The one-year updated data of Cohort 6 submitted in December 2021 to the American Society of Hematology (ASH) indicated that the toxicity management strategy of Cohort 6 could improve specific adverse events without compromising the activity of Yescarta, which helped address the potential issue that steroid use might affect efficacy. Patients in Cohort 4 and Cohort 6 were found to have received a median cumulative steroid dose lower than the median cumulative steroid dose used in the matched Cohort 1/2 receiving steroid treatment for CRS or neurological events.

Frank Neumann, Global Head of Clinical Development at Kite, stated: "These new data will enable physicians to manage patient treatment more easily and with greater confidence. Since the initial approval of Yescarta, Kite has been working closely with physicians to optimize every aspect of CAR-T cell therapy, allowing as many patients as possible to benefit from this treatment. Our responsibility includes expanding research into new diseases and earlier lines of therapy, as well as continuously enhancing the efficacy and safety of our existing CAR-T therapies."

Yescarta (Axicabtagene Ciloleucel, Axi-Cel) is a CD19 CAR-T cell therapy acquired by Gilead Sciences for $11.9 billion through the acquisition of Kite Pharma. In the United States, Yescarta was approved in October 2017.FDAApproved, it is the first CAR-T cell therapy for the treatment of adult patients with relapsed or refractory large B-cell lymphoma (R/R LBLC).

In March 2021, Yescarta was approved in China.FDAApproval of a new indication: for the treatment of adult patients with relapsed or refractory (R/R) follicular lymphoma (FL) who have previously received two or more systemic therapies. Based on this latest approval, Yescarta is the first CAR-T cell therapy approved for the treatment of FL.

In China, in June 2021, the National Medical Products Administration (NMPA) approved FOSUN Kite's axicabtagene ciloleucel injection (trade name: Yikaida) for marketing through the priority review and approval process. This drug is the first cell therapy product to be approved for marketing in China, used for treating adult patients with relapsed or refractory large B-cell lymphoma who have received 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 a product based on Kite Pharma's Yescarta (Axicabtagene Ciloleucel, Axi-Cel), which has undergone technology transfer and is intended for localized production within China (excluding Hong Kong, Macao, and Taiwan). The product was introduced by Fosun Kite from Kite Pharma, which obtained the technical and commercial 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 that Fosun Kite has advanced to commercialization in China, and it is also the first CAR-T cell therapy product officially approved for marketing by the National Medical Products Administration (NMPA). As a completely newTumorTreatment Method: Axicabtagene Ciloleucel Injection (Yikaida) Offers New Hope and Opportunities for Chinese Patients with Relapsed or Refractory Large B-Cell Lymphoma After Receiving Second-Line or Above Systemic Therapy. (Bioon.com)

Source of Original Text:U.S. FDA Approves New Label Update for CAR T-Cell Therapy Yescarta® Showing Prophylactic Steroid Use Improves Management of Cytokine Release Syndrome