Novartis Seeks Second Indication for Tisagenlecleucel: DLBCL

Novartis has filed for an expanded indication for its chimeric antigen receptor (CAR) T-cell treatment, tisagenlecleucel (Kymriah), for use in patients with diffuse large B-cell lymphoma (DLBCL), the most common form of non-Hodgkin’s lymphoma. If approved, the product will compete with axicabtagene ciloleucel (Yescarta)—developed by Kite Pharma, which has been acquired by Gilead Sciences.Yescarta was approved earlier this month in patients with DLBCL who have not responded to or who have relapsed after at least 2 other kinds of treatment.

Kymriah, developed by Novartis, created history when it became the first CAR T treatment to be approved in the United States for the treatment of B-cell precursor acute lymphoblastic leukemia (ALL) in certain pediatric and young adult patients. However, pediatric ALL is a relatively rare disease, with about 3000 new annual diagnoses—this compared with DLBCL, which is estimated to be diagnosed in about 70,000 patients each year in the United States. These numbers provide a perspective on the available market for these gene therapy treatments.

The new filing for Kymriah is based on results from the JULIET trial, a phase 2, single arm, multicenter trial in adult patients with relapsed or refractory DLBCL. Initiated in July 2015, the trial is estimated to continue until January 2024; the primary outcome measure is overall response rate (ORR) and the secondary measures include duration of overall response, progression-free survival, and overall survival, among others.

“The data show this therapy could change the treatment paradigm for patients with r/r DLBCL as we've seen durable complete responses in patients who previously relapsed or were refractory to prior therapies, and this second filing is a significant step toward realizing its potential for even more patients who are currently battling fatal blood cancers,” said Stephen Schuster, MD, director of the Lymphoma Program and Lymphoma Translational Research, University of Pennsylvania Perelman School of Medicine, in a statement.