Novartis has submitted a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) for CTL019 (tisagenlecleucel) for two indications. The application is for the treatment of children and young adults with relapsed or refractory (r/r) B-cell acute lymphoblastic leukemia (ALL) and for adult patients with r/r diffuse large B-cell lymphoma (DLBCL) who are ineligible for autologous stem cell transplant (ASCT). CTL019 is a novel immunocellular therapy and a one-time treatment that uses a patient's own T cells to fight cancer.

"Since the historic FDA approval of Kymriah, formerly CTL019, we have launched, manufactured and supplied this highly individualized immunocelluar therapy in a commercial setting and the submission to the EMA is a major step toward our goal of delivering it to more critically ill cancer patients around the world," said Vas Narasimhan, Global Head of Drug Development and chief medical officer, Novartis. "We look forward to working with the EMA to make CTL019 available to the children and adults who may benefit from this novel therapy."

There has been a dire need for innovative therapies to treat pediatric and young adult patients with r/r B-cell ALL and adult patients with r/r DLBCL, who have few options and historically poor outcomes. DLBCL is the most common subtype of non-Hodgkin lymphoma (NHL), accounting for 40% of all NHL cases globally. If left untreated, r/r DLBCL has a life expectancy of three to four months. In Europe, ALL accounts for approximately 80% of leukemia cases among children. Less than 10% of patients with relapsed or refractory ALL survive five years.

"When tisagenlecleucel became a reality for certain patients and their families in the US after approval by the FDA for patients with relapsed or refractory ALL this year, I believe it forever changed the face of cancer treatment," 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 Penn's Perelman School of Medicine and director of the Lymphoma Program at the Abramson Cancer Center. "The data show this is a groundbreaking immunocellular therapy that has the potential to alter outcomes in patients who have limited options. This submission brings us closer to realizing that potential for more patients with fatal blood cancers."

CTL019 is an innovative immunocellular therapy that is a one-time treatment. CTL019 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 CTL019, for the investigational treatment of cancers.

"For patients in the EU living with these aggressive forms of blood cancer, we have very limited options to improve their chances of sustained remission after their disease has relapsed or become refractory to initial treatment," said Professor Gilles Salles, MD, PhD, Head of Hematology Department, Hospices Civils de Lyon, Lyon, France. "The data for tisagenlecleucel has provided an optimistic look at the potential to achieve durable responses in two distinct and difficult-to-treat patient populations, helping to address a dire unmet need for patients."

The MAA submission is based on the Novartis-sponsored global, multicenter, phase II ELIANA and JULIET trials, which were conducted in collaboration with Penn. ELIANA is the first pediatric global CAR-T cell therapy registration trial, examining patients in 25 centers in the US, Canada, Australia, Japan and the EU, including: Austria, Belgium, France, Germany, Italy Norway, and Spain.

JULIET is the first multi-center global registration study for CTL019 in adult patients with r/r DLBCL. JULIET is the largest study examining a CAR-T therapy exclusively in DLBCL, enrolling patients from 27 sites in 10 countries across the US, Canada, Australia, Japan and Europe, including: Austria, France, Germany, Italy, Norway and the Netherlands. 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 additional regulatory submissions for CTL019 in pediatric and young adult patients with r/r B-cell ALL and adult patients with r/r DLBCL outside the US and EU in 2018.