Type of information: Positive opinion for the granting of a Market Authorisation in the US
Product name: CTL019 (tisagenlecleucel-T)
Therapeutic area: Cancer - Oncology
- cell therapy/gene therapy/CAR-T cell therapy. CTL019 is an investigational, personalized T cell therapy, which was pioneered by Carl June and his team at Penn. In a CTL019 treatment cycle, immune cells (T cells) are drawn from a patient's blood. Then, using CAR technology, the T cells are reprogrammed to "hunt" cancer cells that express specific proteins, called CD19. CTL019 uses the 4-1BB costimulatory domain in its chimeric antigen receptor to enhance cellular responses as well as persistence of CTL019 after it is infused into the patient, which may be associated with long-lasting remissions in patients.
- Novartis and Penn have an exclusive global agreement to research, develop and commercialize personalized CAR T cell therapies for the treatment of cancers. Novartis holds the worldwide rights to CARs developed through the collaboration for all cancer indications, including the lead program CTL019.
Company: Novartis (Switzerland)
Disease: B-cell acute lymphoblastic leukemia (ALL)
- • On July 12, 2017, Novartis announced that the FDA Oncologic Drugs Advisory Committee (ODAC) unanimously (10-0) recommended approval of CTL019 (tisagenlecleucel), an investigational chimeric antigen receptor T cell (CAR-T) therapy, for the treatment of relapsed or refractory (r/r) pediatric and young adult patients with B-cell acute lymphoblastic leukemia.
- The ODAC recommendation is based on review of the CTL019 r/r B-cell ALL development program, which includes the Novartis-led ELIANA study, the first pediatric global CAR-T cell therapy registration trial. Findings from a US multicenter trial and a single site trial examining the safety and efficacy of CTL019 among pediatric and young adult patients with r/r B-cell ALL also supported the recommendation and the Biologics License Application (BLA).
- Earlier this year, Novartis submitted a BLA for CTL019 to the FDA, marking the first submission by Novartis for a CAR-T cell therapy. CTL019 previously received FDA Breakthrough Therapy designation and is under Priority Review by the FDA. The FDA will consider the vote as it reviews the BLA, although it is not obligated to follow the recommendation. Novartis continues to invest in the necessary infrastructure for the potential commercialization of CTL019, including manufacturing and the establishment of a network of certified treatment centers.
- Novartis plans additional filings for CTL019 in the US and EU later this year, including applications with the FDA and European Medicines Agency (EMA) for the treatment of adults with r/r diffuse large B-cell lymphoma.
• On March 29, 2017, Novartis announced that the FDA has accepted the company's Biologics License Application (BLA) filing and granted priority review for CTL019 (tisagenlecleucel-T), in relapsed and refractory (r/r) pediatric and young adult patients with B-cell acute lymphoblastic leukemia. This is the first BLA submission by Novartis for a CAR-T.
- The priority review designation and BLA submission for CTL019 is based on the results from the Novartis-sponsored ELIANA study, the first global CAR-T cell trial with study enrollment having occurred across 25 centers in the US, EU, Canada, Australia and Japan. In the Phase II study, 82% (41 of 50) of patients infused with CAR-T cells achieved complete remission or complete remission with incomplete blood count recovery at three months post CTL019 infusion. The data were presented at the American Society of Hematology meeting in December 2016 (Abstract #221).
- Forty-eight percent of patients in the ELIANA trial experienced grade 3 or 4 cytokine release syndrome (CRS), a known complication of an investigational therapy that may occur when the engineered cells become activated in the patient's body. CRS was managed per protocol on a global scale using prior site education with implementation of the CRS treatment algorithm. There were no deaths due to CRS. Fifteen percent of patients experienced grade 3 neurological and psychiatric events including confusion, delirium, encephalopathy, agitation and seizure. No cerebral edema was reported and no grade 4 neurological and psychiatric events were observed.
- The submission is also supported by findings from a US multicenter trial and an earlier single site trial led by the Children's Hospital of Philadelphia (CHOP) examining the safety and efficacy of CTL019 among pediatric and young adult patients with r/r B-cell ALL. Stephan Grupp, MD, PhD, from CHOP was the lead investigator of the trials.
- CTL019 previously received Breakthrough Therapy designation from the FDA for the treatment of patients with r/r ALL. Novartis plans additional filings for CTL019 in the US and EU markets later this year, including a BLA with the FDA for treatment of adults with r/r diffuse large B-cell lymphoma (DLBCL) and applications for marketing authorization with the European Medicines Agency in r/r B-cell ALL and r/r DLBCL.
Submission of marketing authorization application USA :
Submission of marketing authorization application UE:
Withdrawal of marketing authorization application USA:
Withdrawal of marketing authorization application UE:
Favourable opinion UE:
Favourable opinion USA: 2017-07-12
Orphan status USA:
Orphan status UE:
Pediatric exclusivit _USA:
Pediatric exclusivity UE: