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GEN News Highlights
Novartis’ Kymriah Wins FDA Approval as Very first CAR-T Cancer Therapy
The FDA today approved Novartis` Kymriah (tisagenlecleucel), with the agency hailing the chimeric antigen receptor T-cell (CAR-T) treatment as the very first gene therapy to be available in the U.S.
Kymriah, previously known as CTL019, is indicated for the second-line (or later) treatment of relapsed or refractory (r/r) patients up to age twenty five with B-cell acute lymphoblastic leukemia (ALL).
«With the approval of Kymriah, we are once again delivering on our commitment to switch the course of cancer care,” Novatrtis CEO Joseph Jimenez said in a company statement.
Added FDA Commissioner Scott Gottlieb, M.D., in an agency statement: «We`re coming in a fresh frontier in medical innovation with the capability to reprogram a patient`s own cells to attack a deadly cancer. At the FDA, we`re committed to helping expedite the development and review of groundbreaking treatments that have the potential to be life-saving,» Dr. Gottlieb added.
Novartis is one of two leading developers of CAR-T therapies. The other is Kite Pharma, which is awaiting an FDA decision on its CAR-T treatment axicabtagene ciloleucel (formerly KTE-C19) for treating relapsed or refractory aggressive non-Hodgkin lymphoma (NHL) in patients who are ineligible for autologous stem cell transplant.
Novartis is one of two leading developers of CAR-T therapies. The other is Kite Pharma, which is awaiting an FDA decision on its CAR-T treatment axicabtagene ciloleucel (formerly KTE-C19) for treating relapsed or refractory aggressive non-Hodgkin lymphoma (NHL) in patients who are ineligible for autologous stem cell transplant. Kite has agreed to be acquired by Gilead Sciences for $11.9 billion, a deal announced Monday.
The FDA accepted Novartis` Biologics License Application (BLA) for Kymriah, filed in March 2017, for Priority Review–under which FDA set a objective of taking activity on Novartis` CAR T-cell candidate within six months. The standard review period is ten months.
The FDA acted more than a month ahead of its Prescription Drug User Fee Act (PDUFA) target decision date, which had been set for early October 2017.
In a Twitter tweet, Dr. Gottlieb said the FDA «has granted more than five hundred fifty active INDs related to gene therapy products and seventy six active INDs related to CAR-T cell products.»
Kymriah is not the very first gene therapy ever approved. That distinction was obtained in October two thousand twelve by uniQure`s Glybera, which won European Commission approval to treat hereditary lipoprotein lipase deficiency (LPLD), but whose price tag of €1.1 million ($1.Two million) proved too high. In April, uniQure said it would not renew its European marketing approval for Glybera.
Soon after gaining European approval, uniQure pursued FDA approval, but dropped that effort in two thousand fifteen after the agency requested that the company submit data from more than one clinical probe to support a BLA.
The FDA based its approval of Kymriah on the results of the pivotal Phase II ELIANA trial (NCT02435849), an open-label, multicenter, single-arm examine and the very first pediatric global CAR-T cell therapy registration trial. ELIANA assessed patients in twenty five centers in the U.S, as well as in Europe, Canada, Australia and Japan.
83% Finish Remission
In ELIANA, sixty eight patients were infused and sixty three were evaluable for efficacy. Results demonstrated 83% of patients (52 of 63) who received treatment with Kymriah achieved finish remission (CR) or CR with incomplete blood count recovery (CRi) within three months of infusion. Results among responding patients also showcased no minimal residual disease (MRD), a blood marker that indicates potential relapse.
Novartis also submitted data from a U.S. multicenter trial and a single-site trial examining the safety and efficacy of Kymriah among pediatric and youthful adult patients with r/r B-cell ALL.
The agency`s approval came six weeks after an advisory committee unanimously recommended in favor of the company`s leukemia-fighting treatment.
Very first developed by the University of Pennsylvania, Kymriah uses the 4-1BB costimulatory domain in its CAR to enhance cellular responses as well as persistence of the treatment after it is infused into the patient, which may be associated with long-lasting remissions in patients.
In 2012, Novartis and Penn launched their global collaboration to further research, develop, and commercialize CAR T-cell therapies, including Kymriah, for the investigational treatment of cancers. Children`s Hospital of Philadelphia (CHOP) was the very first institution to investigate Kymriah in the treatment of pediatric patients and led the single-site trial.
«This therapy is a significant step forward in individualized cancer treatment that may have a tremendous influence on patients’ lives,» Carl June, M.D., the leader of the Penn team, said in Novartis` statement. Dr. June is the Richard W. Vague Professor of Immunotherapy, director of the Center for Cellular Immunotherapies in Penn`s Perelman School of Medicine and director of the Parker Institute for Cancer Immunotherapy at Penn.
The FDA acknowledged Kymriah`s potential for severe side effects by approving the treatment with a boxed warning for cytokine release syndrome (CRS), a systemic response to the activation and proliferation of CAR T-cells causing high fever and flu-like symptoms, and for neurological events. Other severe side effects of Kymriah include serious infections, low blood pressure (hypotension), acute kidney injury, fever, and decreased oxygen (hypoxia).
Novartis is also required to conduct a post-marketing observational explore involving patients treated with Kymriah, to further evaluate the long-term safety of the CAR-T therapy.
In its registrational ELIANA trial, 49% of patients treated with Kymriah experienced grade three or four CRS. Also, CRS was among the most common adverse reactions in the trial, along with hypogammaglobulinemia, infections, pyrexia, decreased appetite, headache, encephalopathy, hypotension, bleeding gigs, tachycardia, nausea, diarrhea, vomiting, viral infectious disorders, hypoxia, tiredness, acute kidney injury, and delirium.
The FDA has approved a Risk Evaluation and Mitigation Strategy (REMS) for Kymriah designed to educate healthcare professionals about risks that may be associated with the treatment. Novartis said it will establishing a network of certified treatment centers across the country which will be fully trained on the use of Kymriah and adequate patient care, in order to ensure safe patient access.
$475,000 Price
Novartis plans extra filings for Kymriah in the U.S. and E.U. later this year, including applications with the FDA and European Medicines Agency (EMA), seeking approval for the extra indication of adult patients with r/r diffuse large B-cell lymphoma (DLBCL).
Filings beyond the US and EU are anticipated in 2018, Novartis added.
Novartis has set a $475,000 price for Kymriah–but added it has developed programs to support safe and timely access to the treatment, including support for patients pursuing insurance coverage and financial assistance for uninsured or underinsured patients.
To that end, Novartis also announced a fresh collaboration with the U.S. Centers for Medicare and Medicaid Services (CMS) aimed at ensuring access for Kymriah`s patient population by basing pricing on clinical outcomes–a basis Novartis said would result in «value-based» care through the elimination of inefficiencies.
Other value-based approaches related to future indications for Kymriah and CAR-T cell therapies are under discussion, Novartis said.
The company added that it is working with CMS and private payers to be paid when pediatric and youthful adult ALL patients react to Kymriah by the end of the very first month, with future potential indications to be reviewed for the «most relevant» outcomes-based treatment.
Cost and reimbursement are among key challenges to the development of cell-based therapies, as are commercialization, market access, patient and physician adoption, and manufacturing scale-up, the International Society for Cellular Therapy (ISCT) said in a statement on Kymriah`s approval.
«The approval for CTL019 (tisagenlecleucel) will increase the chance of, and potentially reduce the time for approval for treatments for other critical or fatal diseases with no alternative therapeutic option,» Catherine Bollard, ISCT President and an invited pro to the FDA advisory panel that recommended Kymriah`s approval. «The FDA approval by Novartis is a critical validation of the significant international efforts into the CAR-T field.»
According to the Society, more than forty companies are developing redirected T cells or NK cells for therapeutic use, with more than eight hundred cell therapy clinical trials underway worldwide.
«We are so proud to be part of this historic moment in cancer treatment and are deeply grateful to our researchers, collaborators, and the patients and families who participated in the Kymriah clinical program,» added Bruno Strigini, CEO of Novartis Oncology.
To love more articles like this from GEN, click here to subscribe now!
Novartis – Kymriah Wins FDA Approval as Very first CAR-T Cancer Therapy, GEN
GEN Exclusives
When Protein Characterization Is Used to Monitor Elusive Proteoforms in Elaborate Biological Samples, It Should Be Seen in Start-To-Finish Terms
Modifications to Histones Affect Gene Expression and Cell Fate Decisions
Predictions for 2017
Old Becomes Fresh Again
GEN News Highlights
Novartis’ Kymriah Wins FDA Approval as Very first CAR-T Cancer Therapy
The FDA today approved Novartis` Kymriah (tisagenlecleucel), with the agency hailing the chimeric antigen receptor T-cell (CAR-T) treatment as the very first gene therapy to be available in the U.S.
Kymriah, previously known as CTL019, is indicated for the second-line (or later) treatment of relapsed or refractory (r/r) patients up to age twenty five with B-cell acute lymphoblastic leukemia (ALL).
«With the approval of Kymriah, we are once again delivering on our commitment to switch the course of cancer care,” Novatrtis CEO Joseph Jimenez said in a company statement.
Added FDA Commissioner Scott Gottlieb, M.D., in an agency statement: «We`re injecting a fresh frontier in medical innovation with the capability to reprogram a patient`s own cells to attack a deadly cancer. At the FDA, we`re committed to helping expedite the development and review of groundbreaking treatments that have the potential to be life-saving,» Dr. Gottlieb added.
Novartis is one of two leading developers of CAR-T therapies. The other is Kite Pharma, which is awaiting an FDA decision on its CAR-T treatment axicabtagene ciloleucel (formerly KTE-C19) for treating relapsed or refractory aggressive non-Hodgkin lymphoma (NHL) in patients who are ineligible for autologous stem cell transplant.
Novartis is one of two leading developers of CAR-T therapies. The other is Kite Pharma, which is awaiting an FDA decision on its CAR-T treatment axicabtagene ciloleucel (formerly KTE-C19) for treating relapsed or refractory aggressive non-Hodgkin lymphoma (NHL) in patients who are ineligible for autologous stem cell transplant. Kite has agreed to be acquired by Gilead Sciences for $11.9 billion, a deal announced Monday.
The FDA accepted Novartis` Biologics License Application (BLA) for Kymriah, filed in March 2017, for Priority Review–under which FDA set a purpose of taking activity on Novartis` CAR T-cell candidate within six months. The standard review period is ten months.
The FDA acted more than a month ahead of its Prescription Drug User Fee Act (PDUFA) target decision date, which had been set for early October 2017.
In a Twitter tweet, Dr. Gottlieb said the FDA «has granted more than five hundred fifty active INDs related to gene therapy products and seventy six active INDs related to CAR-T cell products.»
Kymriah is not the very first gene therapy ever approved. That distinction was obtained in October two thousand twelve by uniQure`s Glybera, which won European Commission approval to treat hereditary lipoprotein lipase deficiency (LPLD), but whose price tag of €1.1 million ($1.Two million) proved too high. In April, uniQure said it would not renew its European marketing approval for Glybera.
Soon after gaining European approval, uniQure pursued FDA approval, but dropped that effort in two thousand fifteen after the agency requested that the company submit data from more than one clinical explore to support a BLA.
The FDA based its approval of Kymriah on the results of the pivotal Phase II ELIANA trial (NCT02435849), an open-label, multicenter, single-arm explore and the very first pediatric global CAR-T cell therapy registration trial. ELIANA assessed patients in twenty five centers in the U.S, as well as in Europe, Canada, Australia and Japan.
83% Accomplish Remission
In ELIANA, sixty eight patients were infused and sixty three were evaluable for efficacy. Results showcased 83% of patients (52 of 63) who received treatment with Kymriah achieved accomplish remission (CR) or CR with incomplete blood count recovery (CRi) within three months of infusion. Results among responding patients also displayed no minimal residual disease (MRD), a blood marker that indicates potential relapse.
Novartis also submitted data from a U.S. multicenter trial and a single-site trial examining the safety and efficacy of Kymriah among pediatric and youthful adult patients with r/r B-cell ALL.
The agency`s approval came six weeks after an advisory committee unanimously recommended in favor of the company`s leukemia-fighting treatment.
Very first developed by the University of Pennsylvania, Kymriah uses the 4-1BB costimulatory domain in its CAR to enhance cellular responses as well as persistence of the treatment after it is infused into the patient, which may be associated with long-lasting remissions in patients.
In 2012, Novartis and Penn launched their global collaboration to further research, develop, and commercialize CAR T-cell therapies, including Kymriah, for the investigational treatment of cancers. Children`s Hospital of Philadelphia (CHOP) was the very first institution to investigate Kymriah in the treatment of pediatric patients and led the single-site trial.
«This therapy is a significant step forward in individualized cancer treatment that may have a tremendous influence on patients’ lives,» Carl June, M.D., the leader of the Penn team, said in Novartis` statement. Dr. June is the Richard W. Vague Professor of Immunotherapy, director of the Center for Cellular Immunotherapies in Penn`s Perelman School of Medicine and director of the Parker Institute for Cancer Immunotherapy at Penn.
The FDA acknowledged Kymriah`s potential for severe side effects by approving the treatment with a boxed warning for cytokine release syndrome (CRS), a systemic response to the activation and proliferation of CAR T-cells causing high fever and flu-like symptoms, and for neurological events. Other severe side effects of Kymriah include serious infections, low blood pressure (hypotension), acute kidney injury, fever, and decreased oxygen (hypoxia).
Novartis is also required to conduct a post-marketing observational explore involving patients treated with Kymriah, to further evaluate the long-term safety of the CAR-T therapy.
In its registrational ELIANA trial, 49% of patients treated with Kymriah experienced grade three or four CRS. Also, CRS was among the most common adverse reactions in the trial, along with hypogammaglobulinemia, infections, pyrexia, decreased appetite, headache, encephalopathy, hypotension, bleeding scenes, tachycardia, nausea, diarrhea, vomiting, viral infectious disorders, hypoxia, exhaustion, acute kidney injury, and delirium.
The FDA has approved a Risk Evaluation and Mitigation Strategy (REMS) for Kymriah designed to educate healthcare professionals about risks that may be associated with the treatment. Novartis said it will establishing a network of certified treatment centers across the country which will be fully trained on the use of Kymriah and suitable patient care, in order to ensure safe patient access.
$475,000 Price
Novartis plans extra filings for Kymriah in the U.S. and E.U. later this year, including applications with the FDA and European Medicines Agency (EMA), seeking approval for the extra indication of adult patients with r/r diffuse large B-cell lymphoma (DLBCL).
Filings beyond the US and EU are anticipated in 2018, Novartis added.
Novartis has set a $475,000 price for Kymriah–but added it has developed programs to support safe and timely access to the treatment, including support for patients pursuing insurance coverage and financial assistance for uninsured or underinsured patients.
To that end, Novartis also announced a fresh collaboration with the U.S. Centers for Medicare and Medicaid Services (CMS) aimed at ensuring access for Kymriah`s patient population by basing pricing on clinical outcomes–a basis Novartis said would result in «value-based» care through the elimination of inefficiencies.
Other value-based approaches related to future indications for Kymriah and CAR-T cell therapies are under discussion, Novartis said.
The company added that it is working with CMS and private payers to be paid when pediatric and youthfull adult ALL patients react to Kymriah by the end of the very first month, with future potential indications to be reviewed for the «most relevant» outcomes-based treatment.
Cost and reimbursement are among key challenges to the development of cell-based therapies, as are commercialization, market access, patient and physician adoption, and manufacturing scale-up, the International Society for Cellular Therapy (ISCT) said in a statement on Kymriah`s approval.
«The approval for CTL019 (tisagenlecleucel) will increase the chance of, and potentially reduce the time for approval for treatments for other critical or fatal diseases with no alternative therapeutic option,» Catherine Bollard, ISCT President and an invited accomplished to the FDA advisory panel that recommended Kymriah`s approval. «The FDA approval by Novartis is a critical validation of the significant international efforts into the CAR-T field.»
According to the Society, more than forty companies are developing redirected T cells or NK cells for therapeutic use, with more than eight hundred cell therapy clinical trials underway worldwide.
«We are so proud to be part of this historic moment in cancer treatment and are deeply grateful to our researchers, collaborators, and the patients and families who participated in the Kymriah clinical program,» added Bruno Strigini, CEO of Novartis Oncology.
To love more articles like this from GEN, click here to subscribe now!
Novartis – Kymriah Wins FDA Approval as Very first CAR-T Cancer Therapy, GEN
GEN Exclusives
Fresh Sensors Are Enhancing the Monitoring of Diverse Parameters While Reducing the Need for Extractive Sampling
When Protein Characterization Is Used to Monitor Elusive Proteoforms in Elaborate Biological Samples, It Should Be Seen in Start-To-Finish Terms
Modifications to Histones Affect Gene Expression and Cell Fate Decisions
Predictions for 2017
GEN News Highlights
Novartis’ Kymriah Wins FDA Approval as Very first CAR-T Cancer Therapy
The FDA today approved Novartis` Kymriah (tisagenlecleucel), with the agency hailing the chimeric antigen receptor T-cell (CAR-T) treatment as the very first gene therapy to be available in the U.S.
Kymriah, previously known as CTL019, is indicated for the second-line (or later) treatment of relapsed or refractory (r/r) patients up to age twenty five with B-cell acute lymphoblastic leukemia (ALL).
«With the approval of Kymriah, we are once again delivering on our commitment to switch the course of cancer care,” Novatrtis CEO Joseph Jimenez said in a company statement.
Added FDA Commissioner Scott Gottlieb, M.D., in an agency statement: «We`re coming in a fresh frontier in medical innovation with the capability to reprogram a patient`s own cells to attack a deadly cancer. At the FDA, we`re committed to helping expedite the development and review of groundbreaking treatments that have the potential to be life-saving,» Dr. Gottlieb added.
Novartis is one of two leading developers of CAR-T therapies. The other is Kite Pharma, which is awaiting an FDA decision on its CAR-T treatment axicabtagene ciloleucel (formerly KTE-C19) for treating relapsed or refractory aggressive non-Hodgkin lymphoma (NHL) in patients who are ineligible for autologous stem cell transplant.
Novartis is one of two leading developers of CAR-T therapies. The other is Kite Pharma, which is awaiting an FDA decision on its CAR-T treatment axicabtagene ciloleucel (formerly KTE-C19) for treating relapsed or refractory aggressive non-Hodgkin lymphoma (NHL) in patients who are ineligible for autologous stem cell transplant. Kite has agreed to be acquired by Gilead Sciences for $11.9 billion, a deal announced Monday.
The FDA accepted Novartis` Biologics License Application (BLA) for Kymriah, filed in March 2017, for Priority Review–under which FDA set a aim of taking act on Novartis` CAR T-cell candidate within six months. The standard review period is ten months.
The FDA acted more than a month ahead of its Prescription Drug User Fee Act (PDUFA) target decision date, which had been set for early October 2017.
In a Twitter tweet, Dr. Gottlieb said the FDA «has granted more than five hundred fifty active INDs related to gene therapy products and seventy six active INDs related to CAR-T cell products.»
Kymriah is not the very first gene therapy ever approved. That distinction was obtained in October two thousand twelve by uniQure`s Glybera, which won European Commission approval to treat hereditary lipoprotein lipase deficiency (LPLD), but whose price tag of €1.1 million ($1.Two million) proved too high. In April, uniQure said it would not renew its European marketing approval for Glybera.
Soon after gaining European approval, uniQure pursued FDA approval, but dropped that effort in two thousand fifteen after the agency requested that the company submit data from more than one clinical probe to support a BLA.
The FDA based its approval of Kymriah on the results of the pivotal Phase II ELIANA trial (NCT02435849), an open-label, multicenter, single-arm explore and the very first pediatric global CAR-T cell therapy registration trial. ELIANA assessed patients in twenty five centers in the U.S, as well as in Europe, Canada, Australia and Japan.
83% Finish Remission
In ELIANA, sixty eight patients were infused and sixty three were evaluable for efficacy. Results displayed 83% of patients (52 of 63) who received treatment with Kymriah achieved finish remission (CR) or CR with incomplete blood count recovery (CRi) within three months of infusion. Results among responding patients also displayed no minimal residual disease (MRD), a blood marker that indicates potential relapse.
Novartis also submitted data from a U.S. multicenter trial and a single-site trial examining the safety and efficacy of Kymriah among pediatric and youthfull adult patients with r/r B-cell ALL.
The agency`s approval came six weeks after an advisory committee unanimously recommended in favor of the company`s leukemia-fighting treatment.
Very first developed by the University of Pennsylvania, Kymriah uses the 4-1BB costimulatory domain in its CAR to enhance cellular responses as well as persistence of the treatment after it is infused into the patient, which may be associated with long-lasting remissions in patients.
In 2012, Novartis and Penn launched their global collaboration to further research, develop, and commercialize CAR T-cell therapies, including Kymriah, for the investigational treatment of cancers. Children`s Hospital of Philadelphia (CHOP) was the very first institution to investigate Kymriah in the treatment of pediatric patients and led the single-site trial.
«This therapy is a significant step forward in individualized cancer treatment that may have a tremendous influence on patients’ lives,» Carl June, M.D., the leader of the Penn team, said in Novartis` statement. Dr. June is the Richard W. Vague Professor of Immunotherapy, director of the Center for Cellular Immunotherapies in Penn`s Perelman School of Medicine and director of the Parker Institute for Cancer Immunotherapy at Penn.
The FDA acknowledged Kymriah`s potential for severe side effects by approving the treatment with a boxed warning for cytokine release syndrome (CRS), a systemic response to the activation and proliferation of CAR T-cells causing high fever and flu-like symptoms, and for neurological events. Other severe side effects of Kymriah include serious infections, low blood pressure (hypotension), acute kidney injury, fever, and decreased oxygen (hypoxia).
Novartis is also required to conduct a post-marketing observational probe involving patients treated with Kymriah, to further evaluate the long-term safety of the CAR-T therapy.
In its registrational ELIANA trial, 49% of patients treated with Kymriah experienced grade three or four CRS. Also, CRS was among the most common adverse reactions in the trial, along with hypogammaglobulinemia, infections, pyrexia, decreased appetite, headache, encephalopathy, hypotension, bleeding scenes, tachycardia, nausea, diarrhea, vomiting, viral infectious disorders, hypoxia, tiredness, acute kidney injury, and delirium.
The FDA has approved a Risk Evaluation and Mitigation Strategy (REMS) for Kymriah designed to educate healthcare professionals about risks that may be associated with the treatment. Novartis said it will establishing a network of certified treatment centers via the country which will be fully trained on the use of Kymriah and suitable patient care, in order to ensure safe patient access.
$475,000 Price
Novartis plans extra filings for Kymriah in the U.S. and E.U. later this year, including applications with the FDA and European Medicines Agency (EMA), seeking approval for the extra indication of adult patients with r/r diffuse large B-cell lymphoma (DLBCL).
Filings beyond the US and EU are anticipated in 2018, Novartis added.
Novartis has set a $475,000 price for Kymriah–but added it has developed programs to support safe and timely access to the treatment, including support for patients pursuing insurance coverage and financial assistance for uninsured or underinsured patients.
To that end, Novartis also announced a fresh collaboration with the U.S. Centers for Medicare and Medicaid Services (CMS) aimed at ensuring access for Kymriah`s patient population by basing pricing on clinical outcomes–a basis Novartis said would result in «value-based» care through the elimination of inefficiencies.
Other value-based approaches related to future indications for Kymriah and CAR-T cell therapies are under discussion, Novartis said.
The company added that it is working with CMS and private payers to be paid when pediatric and youthfull adult ALL patients react to Kymriah by the end of the very first month, with future potential indications to be reviewed for the «most relevant» outcomes-based treatment.
Cost and reimbursement are among key challenges to the development of cell-based therapies, as are commercialization, market access, patient and physician adoption, and manufacturing scale-up, the International Society for Cellular Therapy (ISCT) said in a statement on Kymriah`s approval.
«The approval for CTL019 (tisagenlecleucel) will increase the chance of, and potentially reduce the time for approval for treatments for other critical or fatal diseases with no alternative therapeutic option,» Catherine Bollard, ISCT President and an invited accomplished to the FDA advisory panel that recommended Kymriah`s approval. «The FDA approval by Novartis is a critical validation of the significant international efforts into the CAR-T field.»
According to the Society, more than forty companies are developing redirected T cells or NK cells for therapeutic use, with more than eight hundred cell therapy clinical trials underway worldwide.
«We are so proud to be part of this historic moment in cancer treatment and are deeply grateful to our researchers, collaborators, and the patients and families who participated in the Kymriah clinical program,» added Bruno Strigini, CEO of Novartis Oncology.
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