FDA approves first CAR T-cell therapy to treat ALL

Photo courtesy of Novartis

The US Food and Drug Administration (FDA) has approved the first chimeric antigen receptor (CAR) T-cell therapy, tisagenlecleucel (Kymriah^TM, formerly CTL019).

The therapy is approved for use in children and young adults up to 25 years of age who have B-cell precursor acute lymphoblastic leukemia (ALL) that is refractory or in second or later relapse.

Tisagenlecleucel consists of autologous T cells expressing a CD19-specific CAR.

The therapy was first developed by the University of Pennsylvania. In 2012, the university and Novartis entered into a global collaboration to further research, develop, and commercialize CAR T-cell therapies. Novartis holds the worldwide rights to tisagenlecleucel and other therapies developed through the collaboration.

The application for tisagenlecleucel was supported by results from 3 clinical trials:

• A pilot study presented at the 2015 ASH Annual Meeting
• The phase 2 ENSIGN trial, which was presented at the 2016 ASH Annual Meeting
• The phase 2 ELIANA study, which was recently presented at the 22nd Congress of the European Hematology Association (EHA).

Safety concerns

The prescribing information for tisagenlecleucel includes a boxed warning noting that the treatment poses a risk of cytokine release syndrome (CRS) and neurological toxicity, both of which can be life-threatening.

Because of the risk of CRS, the FDA has expanded the approved use of tocilizumab (Actemra) to include treatment of CAR T-cell-induced severe or life-threatening CRS in patients age 2 and older.

The risk of CRS and neurological toxicity also prompted the FDA to approve tisagenlecleucel with a risk evaluation and mitigation strategy (REMS), which includes elements to assure safe use.

The FDA is requiring that hospitals and their associated clinics that dispense tisagenlecleucel be specially certified. As part of that certification, staff involved in the prescribing, dispensing, or administration of tisagenlecleucel are required to be trained to recognize and manage CRS and neurological events.

Additionally, the certified healthcare settings are required to have protocols in place to ensure that tisagenlecleucel is only given to patients after verifying that tocilizumab is available for immediate administration.

The REMS program specifies that patients be informed of the signs and symptoms of CRS and neurological toxicities following infusion and of the importance of promptly returning to the treatment site if they develop fever or other adverse reactions after receiving tisagenlecleucel.

To further evaluate the long-term safety of tisagenlecleucel, Novartis is required to conduct a post-marketing observational study involving patients who received the treatment.

Access and cost

Tisagenlecleucel will be manufactured for each individual patient at Novartis’s facility in Morris Plains, New Jersey.

Novartis said it has designed a manufacturing and supply chain platform that allows for an individualized treatment approach on a global scale. This process includes cryopreservation of a patient’s harvested cells, providing the flexibility to initiate treatment with tisagenlecleucel based on the individual patient’s condition.

Tisagenlecleucel will reportedly cost $475,000 for a single course of treatment. However, Novartis said it will help patients navigate insurance coverage and provide financial assistance for those who are uninsured or underinsured.

In addition, patients will only be required to pay for tisagenlecleucel if they respond within a month of receiving the treatment. This is a result of a collaboration between Novartis and the US Centers for Medicare and Medicaid Services that is focused on delivering value-based care. The approach is intended to include indication-based pricing for medicines and supports payments for a medicine based on the clinical outcomes achieved.

Photo courtesy of Novartis

The US Food and Drug Administration (FDA) has approved the first chimeric antigen receptor (CAR) T-cell therapy, tisagenlecleucel (Kymriah^TM, formerly CTL019).

The therapy is approved for use in children and young adults up to 25 years of age who have B-cell precursor acute lymphoblastic leukemia (ALL) that is refractory or in second or later relapse.

Tisagenlecleucel consists of autologous T cells expressing a CD19-specific CAR.

The therapy was first developed by the University of Pennsylvania. In 2012, the university and Novartis entered into a global collaboration to further research, develop, and commercialize CAR T-cell therapies. Novartis holds the worldwide rights to tisagenlecleucel and other therapies developed through the collaboration.

The application for tisagenlecleucel was supported by results from 3 clinical trials:

• A pilot study presented at the 2015 ASH Annual Meeting
• The phase 2 ENSIGN trial, which was presented at the 2016 ASH Annual Meeting
• The phase 2 ELIANA study, which was recently presented at the 22nd Congress of the European Hematology Association (EHA).

Safety concerns

The prescribing information for tisagenlecleucel includes a boxed warning noting that the treatment poses a risk of cytokine release syndrome (CRS) and neurological toxicity, both of which can be life-threatening.

Because of the risk of CRS, the FDA has expanded the approved use of tocilizumab (Actemra) to include treatment of CAR T-cell-induced severe or life-threatening CRS in patients age 2 and older.

The risk of CRS and neurological toxicity also prompted the FDA to approve tisagenlecleucel with a risk evaluation and mitigation strategy (REMS), which includes elements to assure safe use.

The FDA is requiring that hospitals and their associated clinics that dispense tisagenlecleucel be specially certified. As part of that certification, staff involved in the prescribing, dispensing, or administration of tisagenlecleucel are required to be trained to recognize and manage CRS and neurological events.

Additionally, the certified healthcare settings are required to have protocols in place to ensure that tisagenlecleucel is only given to patients after verifying that tocilizumab is available for immediate administration.

The REMS program specifies that patients be informed of the signs and symptoms of CRS and neurological toxicities following infusion and of the importance of promptly returning to the treatment site if they develop fever or other adverse reactions after receiving tisagenlecleucel.

To further evaluate the long-term safety of tisagenlecleucel, Novartis is required to conduct a post-marketing observational study involving patients who received the treatment.

Access and cost

Tisagenlecleucel will be manufactured for each individual patient at Novartis’s facility in Morris Plains, New Jersey.

Novartis said it has designed a manufacturing and supply chain platform that allows for an individualized treatment approach on a global scale. This process includes cryopreservation of a patient’s harvested cells, providing the flexibility to initiate treatment with tisagenlecleucel based on the individual patient’s condition.

Tisagenlecleucel will reportedly cost $475,000 for a single course of treatment. However, Novartis said it will help patients navigate insurance coverage and provide financial assistance for those who are uninsured or underinsured.

In addition, patients will only be required to pay for tisagenlecleucel if they respond within a month of receiving the treatment. This is a result of a collaboration between Novartis and the US Centers for Medicare and Medicaid Services that is focused on delivering value-based care. The approach is intended to include indication-based pricing for medicines and supports payments for a medicine based on the clinical outcomes achieved.

Photo courtesy of Novartis

The US Food and Drug Administration (FDA) has approved the first chimeric antigen receptor (CAR) T-cell therapy, tisagenlecleucel (Kymriah^TM, formerly CTL019).

The therapy is approved for use in children and young adults up to 25 years of age who have B-cell precursor acute lymphoblastic leukemia (ALL) that is refractory or in second or later relapse.

Tisagenlecleucel consists of autologous T cells expressing a CD19-specific CAR.

The therapy was first developed by the University of Pennsylvania. In 2012, the university and Novartis entered into a global collaboration to further research, develop, and commercialize CAR T-cell therapies. Novartis holds the worldwide rights to tisagenlecleucel and other therapies developed through the collaboration.

The application for tisagenlecleucel was supported by results from 3 clinical trials:

• A pilot study presented at the 2015 ASH Annual Meeting
• The phase 2 ENSIGN trial, which was presented at the 2016 ASH Annual Meeting
• The phase 2 ELIANA study, which was recently presented at the 22nd Congress of the European Hematology Association (EHA).

Safety concerns

The prescribing information for tisagenlecleucel includes a boxed warning noting that the treatment poses a risk of cytokine release syndrome (CRS) and neurological toxicity, both of which can be life-threatening.

Because of the risk of CRS, the FDA has expanded the approved use of tocilizumab (Actemra) to include treatment of CAR T-cell-induced severe or life-threatening CRS in patients age 2 and older.

The risk of CRS and neurological toxicity also prompted the FDA to approve tisagenlecleucel with a risk evaluation and mitigation strategy (REMS), which includes elements to assure safe use.

The FDA is requiring that hospitals and their associated clinics that dispense tisagenlecleucel be specially certified. As part of that certification, staff involved in the prescribing, dispensing, or administration of tisagenlecleucel are required to be trained to recognize and manage CRS and neurological events.

Additionally, the certified healthcare settings are required to have protocols in place to ensure that tisagenlecleucel is only given to patients after verifying that tocilizumab is available for immediate administration.

The REMS program specifies that patients be informed of the signs and symptoms of CRS and neurological toxicities following infusion and of the importance of promptly returning to the treatment site if they develop fever or other adverse reactions after receiving tisagenlecleucel.

To further evaluate the long-term safety of tisagenlecleucel, Novartis is required to conduct a post-marketing observational study involving patients who received the treatment.

Access and cost

Tisagenlecleucel will be manufactured for each individual patient at Novartis’s facility in Morris Plains, New Jersey.

Novartis said it has designed a manufacturing and supply chain platform that allows for an individualized treatment approach on a global scale. This process includes cryopreservation of a patient’s harvested cells, providing the flexibility to initiate treatment with tisagenlecleucel based on the individual patient’s condition.

Tisagenlecleucel will reportedly cost $475,000 for a single course of treatment. However, Novartis said it will help patients navigate insurance coverage and provide financial assistance for those who are uninsured or underinsured.

In addition, patients will only be required to pay for tisagenlecleucel if they respond within a month of receiving the treatment. This is a result of a collaboration between Novartis and the US Centers for Medicare and Medicaid Services that is focused on delivering value-based care. The approach is intended to include indication-based pricing for medicines and supports payments for a medicine based on the clinical outcomes achieved.