Novartis has submitted a supplemental Biologics License Application (sBLA) to the US Food and Drug Administration (FDA) for Kymriah (tisagenlecleucel) suspension for intravenous 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 autologous stem cell transplant (ASCT). In April 2017, Novartis received Breakthrough Therapy designation for r/r DLBCL which, if approved, would be the second indication for Kymriah. In August 2017, Kymriah became the first available chimeric antigen receptor T cell (CAR-T) therapy when it received FDA approval five weeks prior to its PDUFA date and was launched for patients up to 25 years of age with B-cell precursor acute lymphoblastic leukemia (ALL) that is refractory or has relapsed at least twice. Kymriah is a novel immunocellular therapy and a one-time treatment that uses a patient's own T cells to fight cancer.

"Kymriah represents a historic breakthrough in the evolution of individualized immunotherapy and we are committed to bringing this innovation to as many patients who may benefit as possible," said Vas Narasimhan, Global Head of Drug Development and chief medical officer, Novartis. "The response rates we've seen in the JULIET trial show that Kymriah has the potential to transform treatment for these patients and we look forward to collaborating with the FDA to make it available to patients for this second indication."

DLBCL is the most common form of non-Hodgkin lymphoma (NHL), a cancer of the lymphatic system, accounting for up to 40% of all NHL cases globally. Roughly 50-60% of patients with DLBCL achieve and maintain complete remission after first-line therapy; however, roughly one-third of patients relapse after receiving first-line treatment. Only about 25% of patients with r/r DLBCL are eligible for ASCT, the mainstay of secondary treatment. If left untreated, r/r DLBCL has a life expectancy of three to four months.

"The approval of tisagenlecleucel in the treatment of children and young adults with second relapse or refractory B-cell ALL was a watershed moment in the journey for researchers to develop immunocellular therapies," said Stephen Schuster, MD, director of the Lymphoma Program and Lymphoma Translational Research, University of Pennsylvania Perelman School of Medicine. "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."

Kymriah is an innovative immunocellular therapy that is a one-time treatment. Kymriah uses the 4-1BB costimulatory domain in its chimeric antigen receptor to enhance cellular expansion and persistence. In 2012, Novartis and the University of Pennsylvania (Penn) entered into a global collaboration to further research, develop and commercialize CAR-T cell therapies, including Kymriah, for the investigational treatment of cancers.

The submission is based on results from the Novartis-sponsored, global, multi-center phase II JULIET study (NCT02445248), the first global, multi-center registration study for Kymriah in adult patients with r/r DLBCL. JULIET was conducted in collaboration with Penn and is the largest study examining a CAR-T therapy exclusively in DLBCL, enrolling patients from 27 sites in 10 countries across the US, Canada, Europe, Australia and Japan. Data from the six-month primary analysis of JULIET will be presented at the annual meeting of the American Society of Hematology (ASH) in December 2017.

Novartis plans to submit an additional application for marketing authorization for Kymriah with the European Medicines Agency (EMA) in both DLBCL and pediatric ALL later this year. Novartis plans additional regulatory filings for Kymriah outside the US and EU in 2018.