Kite Pharma, a Santa Monica, California-headquartered cell therapy company, has advanced its lead its lead investigational chimeric antigen receptor T cell (CAR-T) therapy, axicabtagene ciloleucel, in safety cohorts of clinical trials in the European Union (EU). The move follows earlier submissions for marketing authorization to the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA). In a separate development, Kite also submitted an investigational new drug application (IND) to the FDA to initiate a Phase I, first-in-human trial of KITE-585, another CAR-T therapy.

Axicabtagene ciloleucel is an investigational therapy in which a patient’s T cells are engineered to express a chimeric antigen receptor to target the antigen CD19, a protein expressed on the cell surface of B-cell lymphomas and leukemias, and redirect the T cells to kill cancer cells.

Kite is currently enrolling in the EU adult patients with relapsed/refractory diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, and transformed follicular lymphoma at multiple EU medical centers. The company initiated the rolling filing in aggressive B-cell non-Hodgkin’s lymphomas in December 2016. In July 2017, Kite filed a marketing authorization application to the European Medicines Agency (EMA) for axicabtagene ciloleucel.

The first patient treated in the safety expansion cohort was at the Academic Medical Center in Amsterdam. Additional patients are expected to be treated in multiple clinical sites across Europe in 2017. Kite has been granted access to Priority Medicines (PRIME) regulatory support in the EU for treating refractory DLBCL. Access to the PRIME initiative is granted by the EMA to support the development and accelerate the review of new therapies to treat patients with a high unmet need.

Axicabtagene ciloleucel is currently under review by the FDA for aggressive non-Hodgkin’s lymphoma and was granted breakthrough therapy designation status for diffuse large B-cell lymphoma, transformed follicular lymphoma, and primary mediastinal B-cell lymphoma. The drug has a FDA action review date of November 29, 2017.

Some analysts have projected near blockbuster status for the drug. A recent analysis by Clarivate Analytics projects near-blockbuster status with sales of more than $900 million in 2021.

In a separate development, Kite submitted a IND to the FDA for KITE-585, a therapy engineered to target B-cell maturation antigen (BCMA) in patients with relapsed/refractory multiple myeloma. It is an anti-BCMA CAR construct designed for high binding affinity to BCMA expressed on the cell surface. KITE-585 contains a receptor derived from a fully human monoclonal antibody and a CD28 protein costimulatory domain intended for optimized T-cell expansion and function. In the presence of cell-bound BCMA, KITE-585 induced polyfunctional T cell expansion, and no tonic signaling in its absence, according to Kite Pharma.

Other companies are advancing CAR T therapies as well. In July 2017, the FDA’s Oncologic Drugs Advisory Committee unanimously recommended for approval Novartis’ CAR-T therapy, CTL019 (tisagenlecleucel), for treating relapsed or refractory pediatric and young adult patients with B-cell acute lymphoblastic leukemia. A biologics license application for this indication is under FDA priority review.

Source: Kite Pharma (Program Initiation) and Kite Pharma (IND Submission)