FDA Grants Priority Review to Novartis's CAR-T Cell Therapy
Novartis announced that the US Food and Drug Administration (FDA) has accepted the company’s Biologics License Application (BLA) filing and granted priority review for CTL019 (tisagenlecleucel-T), an investigational chimeric antigen receptor T cell (CAR-T) therapy, in relapsed and refractory (r/r) pediatric and youthful adult patients with B-cell acute lymphoblastic leukemia (ALL). This is the very first BLA subordination by Novartis for a CAR-T. The priority review designation is expected to shorten the anticipated review time by the FDA.
CAR-T is different from typical puny molecule or biologic therapies presently 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 voicing a particular antigen.
"With CTL019, Novartis is at the forefront of the science and development of immunocellular therapy as a potential fresh innovative treatment to treating certain cancers where there are limited options," said Vas Narasimhan, Global Head of Drug Development and Chief Medical Officer, Novartis. "The priority review and file acceptance of CTL019 by the FDA brings us one step closer to delivering this novel treatment option to children and youthful adults with r/r B-cell ALL in the United States."
CTL019 was very first developed by the University of Pennsylvania. In 2012, Novartis and the University of Pennsylvania entered into a global collaboration to further research, develop and then commercialize CAR-T cell therapies for the investigational treatment of cancers, including CTL019. Through the collaboration, Novartis holds the worldwide rights to CARs developed through the collaboration with the University of Pennsylvania for all cancer indications.
"The past five years have seen tremendous progress in the development and application of cellular engineering in an effort to personalize the treatment of cancer," said the Penn team’s leader, Carl June, MD, director of the Center for Cellular Immunotherapies in the Perelman School of Medicine at the University of Pennsylvania. "We now know that it is possible to treat patients in clinical trials across the world using this treatment, and the results we have observed mark a potential fresh paradigm in the treatment of blood cancers that have not responded to standard therapies."
The priority review designation and BLA obedience for CTL019 is based on the results from the Novartis-sponsored ELIANA explore (NCT02435849), the very first global CAR-T cell trial with probe enrollment having occurred across twenty five centers in the US, EU, Canada, Australia and Japan. In the Phase II explore, 82% (41 of 50) of patients infused with CAR-T cells achieved finish remission or finish remission with incomplete blood count recovery at three months post CTL019 infusion. The data were introduced at the American Society of Hematology meeting in December two thousand sixteen (Abstract #221)[1].
Forty-eight percent of patients in the ELIANA trial experienced grade three or four cytokine release syndrome (CRS), a known complication of an investigational therapy that may occur when the engineered cells become activated in the patient’s assets. 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 three neurological and psychiatric events including confusion, delirium, encephalopathy, agitation and seizure. No cerebral edema was reported and no grade four neurological and psychiatric events were observed[1].
The subordination 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 youthfull adult patients with r/r B-cell ALL. Stephan Grupp, MD, PhD, from CHOP was the lead investigator of the trials.
"Even if a patient has difficult-to-treat relapsed/refractory leukemia, we have seen treatment with CTL019 in clinical trials put cancer into remission," said Grupp, Director of the Cancer Immunotherapy Frontier Program and Director of Translational Research for the Center for Childhood Cancer Research at CHOP. "This could be a first-of-its-kind treatment with titillating potential to help pediatric and youthfull adult r/r B-cell ALL patients."
Acute lymphoblastic leukemia makes up approximately 25% of cancer diagnoses among children under fifteen years old and is the most common childhood cancer in the US[Two]. Patients with r/r ALL have limited treatment options, and the chance of survival for children with the disease who relapse or fail to attain remission is inbetween 16% to 30%[Trio].
According to the FDA guidelines, Priority Review status may potentially shorten the window for the agency to take activity on an application to within six months of the filing acceptance compared to a standard review. The designation aims to prioritize the evaluation of products that have the potential to provide significant improvements in the treatment, diagnosis or prevention of serious conditions when compared to standard applications. CTL019 previously received Breakthrough Therapy designation from the FDA for the treatment of patients with r/r ALL.
Novartis plans extra 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.
Because CTL019 is an investigational therapy, the safety and efficacy profile has not yet been established. Access to investigational therapies is available only through cautiously managed and monitored clinical trials. These trials are designed to better understand the potential benefits and risks of the therapy. Because of the uncertainty of clinical trials, there is no ensure that CTL019 will ever be commercially available anywhere in the world.
FDA Grants Priority Review to Novartis s CAR-T Cell Therapy
FDA Grants Priority Review to Novartis's CAR-T Cell Therapy
Novartis announced that the US Food and Drug Administration (FDA) has accepted the company’s Biologics License Application (BLA) filing and granted priority review for CTL019 (tisagenlecleucel-T), an investigational chimeric antigen receptor T cell (CAR-T) therapy, in relapsed and refractory (r/r) pediatric and youthfull adult patients with B-cell acute lymphoblastic leukemia (ALL). This is the very first BLA conformity by Novartis for a CAR-T. The priority review designation is expected to shorten the anticipated review time by the FDA.
CAR-T is different from typical petite molecule or biologic therapies presently 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 voicing a particular antigen.
"With CTL019, Novartis is at the forefront of the science and development of immunocellular therapy as a potential fresh innovative treatment to treating certain cancers where there are limited options," said Vas Narasimhan, Global Head of Drug Development and Chief Medical Officer, Novartis. "The priority review and file acceptance of CTL019 by the FDA brings us one step closer to delivering this novel treatment option to children and youthful adults with r/r B-cell ALL in the United States."
CTL019 was very first developed by the University of Pennsylvania. In 2012, Novartis and the University of Pennsylvania entered into a global collaboration to further research, develop and then commercialize CAR-T cell therapies for the investigational treatment of cancers, including CTL019. Through the collaboration, Novartis holds the worldwide rights to CARs developed through the collaboration with the University of Pennsylvania for all cancer indications.
"The past five years have seen tremendous progress in the development and application of cellular engineering in an effort to personalize the treatment of cancer," said the Penn team’s leader, Carl June, MD, director of the Center for Cellular Immunotherapies in the Perelman School of Medicine at the University of Pennsylvania. "We now know that it is possible to treat patients in clinical trials across the world using this treatment, and the results we have observed mark a potential fresh paradigm in the treatment of blood cancers that have not responded to standard therapies."
The priority review designation and BLA conformity for CTL019 is based on the results from the Novartis-sponsored ELIANA explore (NCT02435849), the very first global CAR-T cell trial with investigate enrollment having occurred across twenty five centers in the US, EU, Canada, Australia and Japan. In the Phase II investigate, 82% (41 of 50) of patients infused with CAR-T cells achieved accomplish remission or finish remission with incomplete blood count recovery at three months post CTL019 infusion. The data were introduced at the American Society of Hematology meeting in December two thousand sixteen (Abstract #221)[1].
Forty-eight percent of patients in the ELIANA trial experienced grade three or four cytokine release syndrome (CRS), a known complication of an investigational therapy that may occur when the engineered cells become activated in the patient’s assets. 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 three neurological and psychiatric events including confusion, delirium, encephalopathy, agitation and seizure. No cerebral edema was reported and no grade four neurological and psychiatric events were observed[1].
The subordination 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 youthfull adult patients with r/r B-cell ALL. Stephan Grupp, MD, PhD, from CHOP was the lead investigator of the trials.
"Even if a patient has difficult-to-treat relapsed/refractory leukemia, we have seen treatment with CTL019 in clinical trials put cancer into remission," said Grupp, Director of the Cancer Immunotherapy Frontier Program and Director of Translational Research for the Center for Childhood Cancer Research at CHOP. "This could be a first-of-its-kind treatment with arousing potential to help pediatric and youthfull adult r/r B-cell ALL patients."
Acute lymphoblastic leukemia makes up approximately 25% of cancer diagnoses among children under fifteen years old and is the most common childhood cancer in the US[Two]. Patients with r/r ALL have limited treatment options, and the chance of survival for children with the disease who relapse or fail to attain remission is inbetween 16% to 30%[Three].
According to the FDA guidelines, Priority Review status may potentially shorten the window for the agency to take act on an application to within six months of the filing acceptance compared to a standard review. The designation aims to prioritize the evaluation of products that have the potential to provide significant improvements in the treatment, diagnosis or prevention of serious conditions when compared to standard applications. CTL019 previously received Breakthrough Therapy designation from the FDA for the treatment of patients with r/r ALL.
Novartis plans extra 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.
Because CTL019 is an investigational therapy, the safety and efficacy profile has not yet been established. Access to investigational therapies is available only through cautiously managed and monitored clinical trials. These trials are designed to better understand the potential benefits and risks of the therapy. Because of the uncertainty of clinical trials, there is no ensure that CTL019 will ever be commercially available anywhere in the world.
