Novartis’ lymphoma treatment receives FDA breakthrough therapy designation

The US Food and Drug Administration (FDA) has granted Breakthrough Therapy designation to Novartis’ CTL019, an investigational chimeric antigen receptor T cell (CAR-T) therapy, for the treatment of adult patients with relapsed and refractory (r/r) diffuse large B-cell lymphoma (DLBCL), who have failed two or more prior therapies.

This is the second indication for which CTL019 has received this designation; the first being for the treatment of r/r B-cell acute lymphoblastic leukaemia (ALL) in paediatric and young adult patients.

 "At Novartis, we are eager to unlock the full potential of CTL019, including the potential to help patients with r/r DLBCL," said Vas Narasimhan, Global Head of Drug Development and Chief Medical Officer, Novartis.  

CAR-T cell therapy is different from typical small molecule or biologic therapies currently on the market because it is manufactured for each individual patient. During the treatment process, T cells are drawn from a patient’s blood and reprogrammed in the laboratory to create T cells that are genetically coded to hunt the patient’s cancer cells and other B-cells expressing a particular antigen.

Partnership success

CTL019 was first developed by the University of Pennsylvania. In 2012, Novartis and Penn entered into a global collaboration to further research, develop and then commercialise CAR-T cell therapies, including CTL019, for the investigational treatment of cancers. Through the collaboration, Novartis holds the worldwide rights to CARs developed with Penn for all cancer indications.

In March 2017, Novartis announced that the FDA accepted the company’s Biologics License Application filing and granted priority review for CTL019 in the treatment of paediatric and young adult patients with B-cell ALL.

Supporting study

The Breakthrough Therapy designation is based on data from the multi-center Phase II JULIET study, which is evaluating the efficacy and safety of CTL019 in adult patients with r/r DLBCL. JULIET is the second global CAR-T trial, following the Novartis ELIANA study (NCT02435849) investigating CTL019 in r/r B-cell ALL. Findings from JULIET are expected to be presented at an upcoming medical congress.

 "We are encouraged by the FDA’s recognition in the potential of CTL019 for this indication, which follows our promising studies of this therapy for ALL and the FDA filing by Novartis in paediatric and young adult ALL that received priority review," said Carl June MD, University of Pennsylvania.

"Work with our collaborators at trial sites across the world is paving a path to bring personalised cell therapies to more patients with these devastating blood cancers."

DLBCL is the most common form of lymphoma and accounts for approximately 30% of all non-Hodgkin lymphoma cases and 10% – 15% of DLBCL patients fail to respond to initial therapy or relapse within three months of treatment, and an additional 20% – 25% percent relapse after initial response to therapy.

No safety or efficacy established

Because CTL019 is an investigational therapy, the safety and efficacy profile has not yet been established. Access to investigational therapies is available only through carefully controlled and monitored clinical trials. These trials are designed to better understand the potential benefits and risks of the therapy.

Due to the uncertainty of clinical trials, there is no guarantee that CTL019 will ever be commercially available anywhere in the world.