FDA has accepted novartis' application for complementary biologics license for its Car-T cell therapy Kymriah

Novartis' Kymriah (Tisagenlecleucel) for the treatment of relapsed or refractory (R/R) follicular lymphoma (FL) in adults has been accepted for review by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA), respectively.

Previously, the FDA also granted priority review for complementary Biologics Licensing applications (sBLA) for CAR T-cell therapies for this indication. Kymriah has also been granted orphan drug designation by the European Commission. Kymriah is a CD19-directed gene-modified autologous T cell immune cell therapy. Unlike conventional small molecule or biologic therapies, CAR T cell therapy is a live T cell therapy product. Kymriah works by genetically modifying a patient's T cells to express a chimeric antigen receptor (CAR) designed to target the antigen CD19, an antigenic protein expressed on the surface of a variety of blood tumor cells, including B-cell lymphoma and leukemia cells.

Novartis' application is based on data from the Phase II ELARA trial, which investigated the efficacy and safety of Kymriah in adult patients with R /rFL. The study was conducted in patients with relapsed or refractory follicular lymphoma (R/RFL) who had previously received multiple therapies. The complete response rate (CR) and total response rate (ORR) of Kymriah were 65% and 83%, respectively, after at least 3 months of follow-up. For patients in complete remission, the vast majority (90%) of remission lasted ≥6 months. In a statement, Novartis said Kymriah met its primary endpoint of a "strong efficacy response" in a heavily pretreated patient population.

Safety results from the ELARA trial showed no new safety signals for Kymriah. Cytokine release syndrome CRS occurred in 49% of patients, and grade 3 to 4 CRS occurred in none of the patients. In the treatment of CRS, 15% of patients were treated with tocilizumab and 3% with steroids. Neurological events occurred in 9% of patients. Three patients died of progressive disease, and there were no treatment-related deaths. In the ELARA study, 18 percent of patients received Kymriah on an outpatient basis.

"This is an important milestone in Novartis' mission to bring Kymriah to adult patients with relapsed or refractory follicular lymphoma," said Jeff Legos, Executive vice president, Global head of Oncology and hematology development at Novartis. Legos that designated orphan drug designation for the eu and FDA priority review highlighting the patients' unmet clinical needs and urgency, as Kymriah in defeated ELARA trials showed an impressive results, novartis wants to be able to provide a unique and may determine the treatment, in order to minimize the burden.

But trials of the treatment have not been smooth. In August, Novartis announced the failure of a Phase III BELINDA study of Kymriah in patients with aggressive B-cell non-Hodgkin's lymphoma (NHL) who have relapsed or failed to respond to first-line therapy. Compared with standard therapy (SOC), the study failed to meet the primary endpoint of event-free survival. Kymriah is currently approved by the U.S. FDA and the European Union EMA, as well as other regulatory agencies, for the treatment of acute lymphoblastic leukemia (ALL) and diffuse Large B-cell lymphoma (DLBCL) in children and young adults.