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The supplemental Biologics License Application (sBLA) for tisagenlecleucel suspension for IV infusion, formerly CTL019, for the treatment of adult patients with relapsed or refractory (r/r) diffuse large B-cell lymphoma (DLBCL) who are ineligible for or relapse after autologous stem cell transplant has been accepted by the FDA for Priority Review.

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Priority Review is granted to therapies that may provide a significant improvement in the safety and effectiveness of the treatment of a serious disease, and the designation is intended to expedite the standard review time.


Tisagenlecleucel became the first CAR T-cell therapy to receive regulatory approval when it was approved by the FDA in August 2017 for the treatment of patients up to 25 years of age with B-cell precursor ALL that is refractory or in second or later relapse.


Tisagenlecleucel is a novel immunocellular therapy and a one-time treatment that uses a patient's own T cells to fight cancer. It uses the 4-1BB costimulatory domain in its chimeric antigen receptor to enhance cellular expansion and persistence.


The regulatory application is based on data from the global clinical trial program of tisagenlecleucel in children and young adults with r/r B-cell ALL and adult patients with r/r DLBCL demonstrating the efficacy and safety of tisagenlecleucel across studies. Results from the pivotal phase II JULIET clinical trial served as the basis of the sBLA for tisagenlecleucel in adult patients with r/r DLCBL.


JULIET is the first multi-center, global registration study for tisagenlecleucel in adult patients with r/r DLBCL. It is the largest study examining a CAR-T therapy in DLBCL, enrolling patients from 27 sites in 10 countries across the U.S., Canada, Australia, Japan, and Europe, including Austria, France, Germany, Italy, Norway, and the Netherlands.


The data from this pivotal trial shows an overall response rate (ORR) of 53 percent (95% CI, 42%-64%; p<0.0001), with 40 percent achieving a complete response (CR) and 14 percent achieving a partial response among 81 infused patients with 3 or more months of follow-up or earlier discontinuation. At 6 months from infusion, the ORR was 37 percent with a CR rate of 30 percent.


"At the time of trial enrollment, these patients with DLBCL had been through multiple rounds of chemotherapy and many had unsuccessful stem cell transplants, leaving them with few options and a poor prognosis," said the study's principal investigator Stephen J. Schuster, MD, the Robert and Margarita Louis-Dreyfus Professor in Chronic Lymphocytic Leukemia and Lymphoma Clinical Care and Research in the University of Pennsylvania's Perelman School of Medicine and Director of the Lymphoma Program at Penn's Abramson Cancer Center, Philadelphia. "With tisagenlecleucel, we have been able to significantly increase their chance of achieving and maintaining a sustained response without stem cell transplant, demonstrating the therapy's benefit in the treatment of this lethal blood cancer."