Browse result page of ThPDB2
This is the result page of the browse module of ThPDB2. This page gives the information about the query submitted by the user as per the browse category. Further details of the entries can be seen by clicking on the ID or THPP_ID. Further the user can sort the entries on the basis of various fields by clicking on the respective headers. The user can also download the results in various formats.
Tabular representation:
| ID | THPP_ID | Therapeutic Name | Sequence | Molecular Weight | Chemical Formula | Isoelectric Point | Hydrophobicity | Melting Point | Half Life | Description | Disease/Indication | Pharmacodynamics | Mechanism of Action | Toxicity | Metabolism | Absorption | Volume of Distribution | Clearance | Categories | Patent Number | Date of Issue | Date of Expiry | Drug Interaction | Target | Brand Name | Company | Brand Description | Prescribed for | Chemical Name | Formulation | Physical Appearance | Route of Administation | Recommended Dosage | Contraindication | Side Effects | Useful Links 1 | Useful Links 2 | Remarks |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 15583 | Th1610 | Emapalumab | >Th1610_Emapalumab EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKDGSSGWYVPHWFDPWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | 154400 | C6430H9898N1718O2038S46 | 6.6 - 7.2 | NA | 78 ºC | Emapalumab elimination half-life is of approximately 22 days in healthy subjects and it ranges between 2.5-18.9 in HLH patients.[FDA label] | Emapalumab, also known as NI-0501, is a fully human monoclonal antibody that targets interferon gamma. Emapalumab development was sponsored by NovImmune SA, further developed by Sobi and FDA approved on November 20, 2018.[A38676, L4840] The approval of emapalumab was followed by the designation of orphan drug, priority review and breakthrough therapy.[L4840] As well, emapalumab was given the status of PRIME by the EMA.[L4845] | Emapalumab is indicated for the treatment of pediatric and adult patients with primary hemophagocytic lymphohistiocytosis (HLH) with refractory, recurrent or progressive disease or intolerance to conventional HLH therapy.[L4840] The HLH condition is a hyperinflammatory status characterized by the overwhelming activation of normal T lymphocytes and macrophages which can lead to disturbances in the hematology profile and even death. As part of the condition profile, there have been reports proving a massive overexpression of interferon-gamma which is thought to drive the immune hyperactivation leading to organ failure.[A38676] This condition is usually developed and present the symptomatic profile within the first months or years of life. These symptoms consist of fever, enlarged liver or spleen and a lower number of blood cells.[L4840] | In phase 2/3 clinical trials, emapalumab administered concomitantly with dexamethasone reported an overall response in 63% of the patients. The overall response was defined as achievement of a complete or partial response or HLH improvement.[L4841] In this trial and as a proof of interferon-gamma neutralization, there was registered a sharp decrease in serum CXCL9 and to avoid QT prolongation in the presence of low doses of emapalumab.[L4846] | Emapalumab acts by binding and neutralizing interferon-gamma.[A38676] The specific interaction between emapalumab and interferon-gamma produces an inhibition in the interaction between interferon-gamma and its cognate receptor on T-cells which produces the neutralizing activity.[L4845] It is important to consider that emapalumab inhibits both free and IFNGR1-bound interferon-gamma as well as the interaction with IFNGR1 and IFNGR2 at the cell surface.[A40061] HLH is an immune dysregulation syndrome in which several cytokines are involved but it has been reported that interferon-gamma plays a pivotal role in the development of this disease as studies have shown a vast increase in the interferon-gamma levels in HLH patients.[A40059] | There are no reported effects in male or female reproductive organs after an 8- or 13-week repeat-dose toxicity study in animals.[FDA label] | Monoclonal antibodies are thought to be internalized in endothelial cells bound to Fc receptor and rescued from metabolism by recycling. Later, they are degraded in the reticuloendothelial system to small peptides and amino acids which can be used for de-novo protein synthesis.[A31470] | In clinical pharmacokinetic studies, a dose of 1 mg/kg of emapalumab was administered which generated a peak concentration at steady state of 44 mcg/ml and a median steady-state concentration of 25 mcg/ml. The serum concentration of emapalumab increases proportionally between a dose of 1-3 mg/kg and the steady-state is attained by the 7th infusion.[FDA label] | The central and peripheral volume of distribution of emapalumab are 4.2 and 5.6 L, respectively.[FDA label] | Emapalumab clearance is reported to be 0.007 L/h in healthy subjects. This clearance rate can vary in HLH patients depending on the production of interferon-gamma.[FDA label] | Agents reducing cytokine levels | NA | NA | NA | NA | Interferon gamma | Gamifant | SWEDISH ORPHAN BIOVITRUM AB (PUBL) | SWEDISH ORPHAN BIOVITRUM AB (PUBL) | Intravenous | 10 mg/2mL | None. | infections, high blood pressure (hypertension), infusion-related reactions (rash, redness, and increased sweating), fever, low blood potassium (hypokalemia), constipation, abdominal pain, cytomegalovirus infection, diarrhea, increased white blood cells, cough, irritability, fast heart rate, and rapid/shallow breathing | Gamifant is used together with a medicine called dexamethasone to treat hemophagocytic lymphohistiocytosis (HLH), a rare disease that is sometimes inherited. HLH causes your immune system to attack healthy blood cells, which can lead to serious or life-threatening side effects on your spleen or liver.... | Gamifant is a prescription medicine used to treat the symptoms of Hemophagocytic Lymphohistiocytosis. Gamifant may be used alone or with other medications. | NA | GAMIFANT (emapalumab-lzsg) injection for intravenous use is a sterile, preservative-free, clear to slightly opalescent, colorless to slightly yellow solution provided in single-dose vials that require dilution prior to intravenous infusion. | Link | Link | NA |
| 15584 | Th1610 | Emapalumab | >Th1610_Emapalumab EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKDGSSGWYVPHWFDPWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | 154400 | C6430H9898N1718O2038S46 | 6.6 - 7.2 | NA | 78 ºC | Emapalumab elimination half-life is of approximately 22 days in healthy subjects and it ranges between 2.5-18.9 in HLH patients.[FDA label] | Emapalumab, also known as NI-0501, is a fully human monoclonal antibody that targets interferon gamma. Emapalumab development was sponsored by NovImmune SA, further developed by Sobi and FDA approved on November 20, 2018.[A38676, L4840] The approval of emapalumab was followed by the designation of orphan drug, priority review and breakthrough therapy.[L4840] As well, emapalumab was given the status of PRIME by the EMA.[L4845] | Emapalumab is indicated for the treatment of pediatric and adult patients with primary hemophagocytic lymphohistiocytosis (HLH) with refractory, recurrent or progressive disease or intolerance to conventional HLH therapy.[L4840] The HLH condition is a hyperinflammatory status characterized by the overwhelming activation of normal T lymphocytes and macrophages which can lead to disturbances in the hematology profile and even death. As part of the condition profile, there have been reports proving a massive overexpression of interferon-gamma which is thought to drive the immune hyperactivation leading to organ failure.[A38676] This condition is usually developed and present the symptomatic profile within the first months or years of life. These symptoms consist of fever, enlarged liver or spleen and a lower number of blood cells.[L4840] | In phase 2/3 clinical trials, emapalumab administered concomitantly with dexamethasone reported an overall response in 63% of the patients. The overall response was defined as achievement of a complete or partial response or HLH improvement.[L4841] In this trial and as a proof of interferon-gamma neutralization, there was registered a sharp decrease in serum CXCL9 and to avoid QT prolongation in the presence of low doses of emapalumab.[L4846] | Emapalumab acts by binding and neutralizing interferon-gamma.[A38676] The specific interaction between emapalumab and interferon-gamma produces an inhibition in the interaction between interferon-gamma and its cognate receptor on T-cells which produces the neutralizing activity.[L4845] It is important to consider that emapalumab inhibits both free and IFNGR1-bound interferon-gamma as well as the interaction with IFNGR1 and IFNGR2 at the cell surface.[A40061] HLH is an immune dysregulation syndrome in which several cytokines are involved but it has been reported that interferon-gamma plays a pivotal role in the development of this disease as studies have shown a vast increase in the interferon-gamma levels in HLH patients.[A40059] | There are no reported effects in male or female reproductive organs after an 8- or 13-week repeat-dose toxicity study in animals.[FDA label] | Monoclonal antibodies are thought to be internalized in endothelial cells bound to Fc receptor and rescued from metabolism by recycling. Later, they are degraded in the reticuloendothelial system to small peptides and amino acids which can be used for de-novo protein synthesis.[A31470] | In clinical pharmacokinetic studies, a dose of 1 mg/kg of emapalumab was administered which generated a peak concentration at steady state of 44 mcg/ml and a median steady-state concentration of 25 mcg/ml. The serum concentration of emapalumab increases proportionally between a dose of 1-3 mg/kg and the steady-state is attained by the 7th infusion.[FDA label] | The central and peripheral volume of distribution of emapalumab are 4.2 and 5.6 L, respectively.[FDA label] | Emapalumab clearance is reported to be 0.007 L/h in healthy subjects. This clearance rate can vary in HLH patients depending on the production of interferon-gamma.[FDA label] | Amino Acids, Peptides, and Proteins | NA | NA | NA | NA | Interferon gamma | Gamifant | SWEDISH ORPHAN BIOVITRUM AB (PUBL) | SWEDISH ORPHAN BIOVITRUM AB (PUBL) | Intravenous | 50 mg/10mL | None. | infections, high blood pressure (hypertension), infusion-related reactions (rash, redness, and increased sweating), fever, low blood potassium (hypokalemia), constipation, abdominal pain, cytomegalovirus infection, diarrhea, increased white blood cells, cough, irritability, fast heart rate, and rapid/shallow breathing | Gamifant is used together with a medicine called dexamethasone to treat hemophagocytic lymphohistiocytosis (HLH), a rare disease that is sometimes inherited. HLH causes your immune system to attack healthy blood cells, which can lead to serious or life-threatening side effects on your spleen or liver.... | Gamifant is a prescription medicine used to treat the symptoms of Hemophagocytic Lymphohistiocytosis. Gamifant may be used alone or with other medications. | NA | GAMIFANT (emapalumab-lzsg) injection for intravenous use is a sterile, preservative-free, clear to slightly opalescent, colorless to slightly yellow solution provided in single-dose vials that require dilution prior to intravenous infusion. | Link | Link | NA |
| 15585 | Th1610 | Emapalumab | >Th1610_Emapalumab EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKDGSSGWYVPHWFDPWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | 154400 | C6430H9898N1718O2038S46 | 6.6 - 7.2 | NA | 78 ºC | Emapalumab elimination half-life is of approximately 22 days in healthy subjects and it ranges between 2.5-18.9 in HLH patients.[FDA label] | Emapalumab, also known as NI-0501, is a fully human monoclonal antibody that targets interferon gamma. Emapalumab development was sponsored by NovImmune SA, further developed by Sobi and FDA approved on November 20, 2018.[A38676, L4840] The approval of emapalumab was followed by the designation of orphan drug, priority review and breakthrough therapy.[L4840] As well, emapalumab was given the status of PRIME by the EMA.[L4845] | Emapalumab is indicated for the treatment of pediatric and adult patients with primary hemophagocytic lymphohistiocytosis (HLH) with refractory, recurrent or progressive disease or intolerance to conventional HLH therapy.[L4840] The HLH condition is a hyperinflammatory status characterized by the overwhelming activation of normal T lymphocytes and macrophages which can lead to disturbances in the hematology profile and even death. As part of the condition profile, there have been reports proving a massive overexpression of interferon-gamma which is thought to drive the immune hyperactivation leading to organ failure.[A38676] This condition is usually developed and present the symptomatic profile within the first months or years of life. These symptoms consist of fever, enlarged liver or spleen and a lower number of blood cells.[L4840] | In phase 2/3 clinical trials, emapalumab administered concomitantly with dexamethasone reported an overall response in 63% of the patients. The overall response was defined as achievement of a complete or partial response or HLH improvement.[L4841] In this trial and as a proof of interferon-gamma neutralization, there was registered a sharp decrease in serum CXCL9 and to avoid QT prolongation in the presence of low doses of emapalumab.[L4846] | Emapalumab acts by binding and neutralizing interferon-gamma.[A38676] The specific interaction between emapalumab and interferon-gamma produces an inhibition in the interaction between interferon-gamma and its cognate receptor on T-cells which produces the neutralizing activity.[L4845] It is important to consider that emapalumab inhibits both free and IFNGR1-bound interferon-gamma as well as the interaction with IFNGR1 and IFNGR2 at the cell surface.[A40061] HLH is an immune dysregulation syndrome in which several cytokines are involved but it has been reported that interferon-gamma plays a pivotal role in the development of this disease as studies have shown a vast increase in the interferon-gamma levels in HLH patients.[A40059] | There are no reported effects in male or female reproductive organs after an 8- or 13-week repeat-dose toxicity study in animals.[FDA label] | Monoclonal antibodies are thought to be internalized in endothelial cells bound to Fc receptor and rescued from metabolism by recycling. Later, they are degraded in the reticuloendothelial system to small peptides and amino acids which can be used for de-novo protein synthesis.[A31470] | In clinical pharmacokinetic studies, a dose of 1 mg/kg of emapalumab was administered which generated a peak concentration at steady state of 44 mcg/ml and a median steady-state concentration of 25 mcg/ml. The serum concentration of emapalumab increases proportionally between a dose of 1-3 mg/kg and the steady-state is attained by the 7th infusion.[FDA label] | The central and peripheral volume of distribution of emapalumab are 4.2 and 5.6 L, respectively.[FDA label] | Emapalumab clearance is reported to be 0.007 L/h in healthy subjects. This clearance rate can vary in HLH patients depending on the production of interferon-gamma.[FDA label] | Antibodies | NA | NA | NA | NA | Interferon gamma | Gamifant | NovImmune SA | NovImmune SA | Intravenous | 10 mg/2mL | None. | infections, high blood pressure (hypertension), infusion-related reactions (rash, redness, and increased sweating), fever, low blood potassium (hypokalemia), constipation, abdominal pain, cytomegalovirus infection, diarrhea, increased white blood cells, cough, irritability, fast heart rate, and rapid/shallow breathing | Gamifant is used together with a medicine called dexamethasone to treat hemophagocytic lymphohistiocytosis (HLH), a rare disease that is sometimes inherited. HLH causes your immune system to attack healthy blood cells, which can lead to serious or life-threatening side effects on your spleen or liver.... | Gamifant is a prescription medicine used to treat the symptoms of Hemophagocytic Lymphohistiocytosis. Gamifant may be used alone or with other medications. | NA | GAMIFANT (emapalumab-lzsg) injection for intravenous use is a sterile, preservative-free, clear to slightly opalescent, colorless to slightly yellow solution provided in single-dose vials that require dilution prior to intravenous infusion. | Link | Link | NA |
| 15586 | Th1610 | Emapalumab | >Th1610_Emapalumab EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKDGSSGWYVPHWFDPWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | 154400 | C6430H9898N1718O2038S46 | 6.6 - 7.2 | NA | 78 ºC | Emapalumab elimination half-life is of approximately 22 days in healthy subjects and it ranges between 2.5-18.9 in HLH patients.[FDA label] | Emapalumab, also known as NI-0501, is a fully human monoclonal antibody that targets interferon gamma. Emapalumab development was sponsored by NovImmune SA, further developed by Sobi and FDA approved on November 20, 2018.[A38676, L4840] The approval of emapalumab was followed by the designation of orphan drug, priority review and breakthrough therapy.[L4840] As well, emapalumab was given the status of PRIME by the EMA.[L4845] | Emapalumab is indicated for the treatment of pediatric and adult patients with primary hemophagocytic lymphohistiocytosis (HLH) with refractory, recurrent or progressive disease or intolerance to conventional HLH therapy.[L4840] The HLH condition is a hyperinflammatory status characterized by the overwhelming activation of normal T lymphocytes and macrophages which can lead to disturbances in the hematology profile and even death. As part of the condition profile, there have been reports proving a massive overexpression of interferon-gamma which is thought to drive the immune hyperactivation leading to organ failure.[A38676] This condition is usually developed and present the symptomatic profile within the first months or years of life. These symptoms consist of fever, enlarged liver or spleen and a lower number of blood cells.[L4840] | In phase 2/3 clinical trials, emapalumab administered concomitantly with dexamethasone reported an overall response in 63% of the patients. The overall response was defined as achievement of a complete or partial response or HLH improvement.[L4841] In this trial and as a proof of interferon-gamma neutralization, there was registered a sharp decrease in serum CXCL9 and to avoid QT prolongation in the presence of low doses of emapalumab.[L4846] | Emapalumab acts by binding and neutralizing interferon-gamma.[A38676] The specific interaction between emapalumab and interferon-gamma produces an inhibition in the interaction between interferon-gamma and its cognate receptor on T-cells which produces the neutralizing activity.[L4845] It is important to consider that emapalumab inhibits both free and IFNGR1-bound interferon-gamma as well as the interaction with IFNGR1 and IFNGR2 at the cell surface.[A40061] HLH is an immune dysregulation syndrome in which several cytokines are involved but it has been reported that interferon-gamma plays a pivotal role in the development of this disease as studies have shown a vast increase in the interferon-gamma levels in HLH patients.[A40059] | There are no reported effects in male or female reproductive organs after an 8- or 13-week repeat-dose toxicity study in animals.[FDA label] | Monoclonal antibodies are thought to be internalized in endothelial cells bound to Fc receptor and rescued from metabolism by recycling. Later, they are degraded in the reticuloendothelial system to small peptides and amino acids which can be used for de-novo protein synthesis.[A31470] | In clinical pharmacokinetic studies, a dose of 1 mg/kg of emapalumab was administered which generated a peak concentration at steady state of 44 mcg/ml and a median steady-state concentration of 25 mcg/ml. The serum concentration of emapalumab increases proportionally between a dose of 1-3 mg/kg and the steady-state is attained by the 7th infusion.[FDA label] | The central and peripheral volume of distribution of emapalumab are 4.2 and 5.6 L, respectively.[FDA label] | Emapalumab clearance is reported to be 0.007 L/h in healthy subjects. This clearance rate can vary in HLH patients depending on the production of interferon-gamma.[FDA label] | Antibodies, Monoclonal | NA | NA | NA | NA | Interferon gamma | Gamifant | NovImmune SA | NovImmune SA | Intravenous | 50 mg/10mL | None. | infections, high blood pressure (hypertension), infusion-related reactions (rash, redness, and increased sweating), fever, low blood potassium (hypokalemia), constipation, abdominal pain, cytomegalovirus infection, diarrhea, increased white blood cells, cough, irritability, fast heart rate, and rapid/shallow breathing | Gamifant is used together with a medicine called dexamethasone to treat hemophagocytic lymphohistiocytosis (HLH), a rare disease that is sometimes inherited. HLH causes your immune system to attack healthy blood cells, which can lead to serious or life-threatening side effects on your spleen or liver.... | Gamifant is a prescription medicine used to treat the symptoms of Hemophagocytic Lymphohistiocytosis. Gamifant may be used alone or with other medications. | NA | GAMIFANT (emapalumab-lzsg) injection for intravenous use is a sterile, preservative-free, clear to slightly opalescent, colorless to slightly yellow solution provided in single-dose vials that require dilution prior to intravenous infusion. | Link | Link | NA |
| 15587 | Th1610 | Emapalumab | >Th1610_Emapalumab EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKDGSSGWYVPHWFDPWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | 154400 | C6430H9898N1718O2038S46 | 6.6 - 7.2 | NA | 78 ºC | Emapalumab elimination half-life is of approximately 22 days in healthy subjects and it ranges between 2.5-18.9 in HLH patients.[FDA label] | Emapalumab, also known as NI-0501, is a fully human monoclonal antibody that targets interferon gamma. Emapalumab development was sponsored by NovImmune SA, further developed by Sobi and FDA approved on November 20, 2018.[A38676, L4840] The approval of emapalumab was followed by the designation of orphan drug, priority review and breakthrough therapy.[L4840] As well, emapalumab was given the status of PRIME by the EMA.[L4845] | Emapalumab is indicated for the treatment of pediatric and adult patients with primary hemophagocytic lymphohistiocytosis (HLH) with refractory, recurrent or progressive disease or intolerance to conventional HLH therapy.[L4840] The HLH condition is a hyperinflammatory status characterized by the overwhelming activation of normal T lymphocytes and macrophages which can lead to disturbances in the hematology profile and even death. As part of the condition profile, there have been reports proving a massive overexpression of interferon-gamma which is thought to drive the immune hyperactivation leading to organ failure.[A38676] This condition is usually developed and present the symptomatic profile within the first months or years of life. These symptoms consist of fever, enlarged liver or spleen and a lower number of blood cells.[L4840] | In phase 2/3 clinical trials, emapalumab administered concomitantly with dexamethasone reported an overall response in 63% of the patients. The overall response was defined as achievement of a complete or partial response or HLH improvement.[L4841] In this trial and as a proof of interferon-gamma neutralization, there was registered a sharp decrease in serum CXCL9 and to avoid QT prolongation in the presence of low doses of emapalumab.[L4846] | Emapalumab acts by binding and neutralizing interferon-gamma.[A38676] The specific interaction between emapalumab and interferon-gamma produces an inhibition in the interaction between interferon-gamma and its cognate receptor on T-cells which produces the neutralizing activity.[L4845] It is important to consider that emapalumab inhibits both free and IFNGR1-bound interferon-gamma as well as the interaction with IFNGR1 and IFNGR2 at the cell surface.[A40061] HLH is an immune dysregulation syndrome in which several cytokines are involved but it has been reported that interferon-gamma plays a pivotal role in the development of this disease as studies have shown a vast increase in the interferon-gamma levels in HLH patients.[A40059] | There are no reported effects in male or female reproductive organs after an 8- or 13-week repeat-dose toxicity study in animals.[FDA label] | Monoclonal antibodies are thought to be internalized in endothelial cells bound to Fc receptor and rescued from metabolism by recycling. Later, they are degraded in the reticuloendothelial system to small peptides and amino acids which can be used for de-novo protein synthesis.[A31470] | In clinical pharmacokinetic studies, a dose of 1 mg/kg of emapalumab was administered which generated a peak concentration at steady state of 44 mcg/ml and a median steady-state concentration of 25 mcg/ml. The serum concentration of emapalumab increases proportionally between a dose of 1-3 mg/kg and the steady-state is attained by the 7th infusion.[FDA label] | The central and peripheral volume of distribution of emapalumab are 4.2 and 5.6 L, respectively.[FDA label] | Emapalumab clearance is reported to be 0.007 L/h in healthy subjects. This clearance rate can vary in HLH patients depending on the production of interferon-gamma.[FDA label] | Antineoplastic and Immunomodulating Agents | NA | NA | NA | NA | Interferon gamma | Gamifant | SWEDISH ORPHAN BIOVITRUM AB (PUBL) | SWEDISH ORPHAN BIOVITRUM AB (PUBL) | Intravenous | 100 mg/20mL | None. | infections, high blood pressure (hypertension), infusion-related reactions (rash, redness, and increased sweating), fever, low blood potassium (hypokalemia), constipation, abdominal pain, cytomegalovirus infection, diarrhea, increased white blood cells, cough, irritability, fast heart rate, and rapid/shallow breathing | Gamifant is used together with a medicine called dexamethasone to treat hemophagocytic lymphohistiocytosis (HLH), a rare disease that is sometimes inherited. HLH causes your immune system to attack healthy blood cells, which can lead to serious or life-threatening side effects on your spleen or liver.... | Gamifant is a prescription medicine used to treat the symptoms of Hemophagocytic Lymphohistiocytosis. Gamifant may be used alone or with other medications. | NA | GAMIFANT (emapalumab-lzsg) injection for intravenous use is a sterile, preservative-free, clear to slightly opalescent, colorless to slightly yellow solution provided in single-dose vials that require dilution prior to intravenous infusion. | Link | Link | NA |
| 15588 | Th1610 | Emapalumab | >Th1610_Emapalumab EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKDGSSGWYVPHWFDPWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | 154400 | C6430H9898N1718O2038S46 | 6.6 - 7.2 | NA | 78 ºC | Emapalumab elimination half-life is of approximately 22 days in healthy subjects and it ranges between 2.5-18.9 in HLH patients.[FDA label] | Emapalumab, also known as NI-0501, is a fully human monoclonal antibody that targets interferon gamma. Emapalumab development was sponsored by NovImmune SA, further developed by Sobi and FDA approved on November 20, 2018.[A38676, L4840] The approval of emapalumab was followed by the designation of orphan drug, priority review and breakthrough therapy.[L4840] As well, emapalumab was given the status of PRIME by the EMA.[L4845] | Emapalumab is indicated for the treatment of pediatric and adult patients with primary hemophagocytic lymphohistiocytosis (HLH) with refractory, recurrent or progressive disease or intolerance to conventional HLH therapy.[L4840] The HLH condition is a hyperinflammatory status characterized by the overwhelming activation of normal T lymphocytes and macrophages which can lead to disturbances in the hematology profile and even death. As part of the condition profile, there have been reports proving a massive overexpression of interferon-gamma which is thought to drive the immune hyperactivation leading to organ failure.[A38676] This condition is usually developed and present the symptomatic profile within the first months or years of life. These symptoms consist of fever, enlarged liver or spleen and a lower number of blood cells.[L4840] | In phase 2/3 clinical trials, emapalumab administered concomitantly with dexamethasone reported an overall response in 63% of the patients. The overall response was defined as achievement of a complete or partial response or HLH improvement.[L4841] In this trial and as a proof of interferon-gamma neutralization, there was registered a sharp decrease in serum CXCL9 and to avoid QT prolongation in the presence of low doses of emapalumab.[L4846] | Emapalumab acts by binding and neutralizing interferon-gamma.[A38676] The specific interaction between emapalumab and interferon-gamma produces an inhibition in the interaction between interferon-gamma and its cognate receptor on T-cells which produces the neutralizing activity.[L4845] It is important to consider that emapalumab inhibits both free and IFNGR1-bound interferon-gamma as well as the interaction with IFNGR1 and IFNGR2 at the cell surface.[A40061] HLH is an immune dysregulation syndrome in which several cytokines are involved but it has been reported that interferon-gamma plays a pivotal role in the development of this disease as studies have shown a vast increase in the interferon-gamma levels in HLH patients.[A40059] | There are no reported effects in male or female reproductive organs after an 8- or 13-week repeat-dose toxicity study in animals.[FDA label] | Monoclonal antibodies are thought to be internalized in endothelial cells bound to Fc receptor and rescued from metabolism by recycling. Later, they are degraded in the reticuloendothelial system to small peptides and amino acids which can be used for de-novo protein synthesis.[A31470] | In clinical pharmacokinetic studies, a dose of 1 mg/kg of emapalumab was administered which generated a peak concentration at steady state of 44 mcg/ml and a median steady-state concentration of 25 mcg/ml. The serum concentration of emapalumab increases proportionally between a dose of 1-3 mg/kg and the steady-state is attained by the 7th infusion.[FDA label] | The central and peripheral volume of distribution of emapalumab are 4.2 and 5.6 L, respectively.[FDA label] | Emapalumab clearance is reported to be 0.007 L/h in healthy subjects. This clearance rate can vary in HLH patients depending on the production of interferon-gamma.[FDA label] | Blood Proteins | NA | NA | NA | NA | Interferon gamma | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 15589 | Th1610 | Emapalumab | >Th1610_Emapalumab EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKDGSSGWYVPHWFDPWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | 154400 | C6430H9898N1718O2038S46 | 6.6 - 7.2 | NA | 78 ºC | Emapalumab elimination half-life is of approximately 22 days in healthy subjects and it ranges between 2.5-18.9 in HLH patients.[FDA label] | Emapalumab, also known as NI-0501, is a fully human monoclonal antibody that targets interferon gamma. Emapalumab development was sponsored by NovImmune SA, further developed by Sobi and FDA approved on November 20, 2018.[A38676, L4840] The approval of emapalumab was followed by the designation of orphan drug, priority review and breakthrough therapy.[L4840] As well, emapalumab was given the status of PRIME by the EMA.[L4845] | Emapalumab is indicated for the treatment of pediatric and adult patients with primary hemophagocytic lymphohistiocytosis (HLH) with refractory, recurrent or progressive disease or intolerance to conventional HLH therapy.[L4840] The HLH condition is a hyperinflammatory status characterized by the overwhelming activation of normal T lymphocytes and macrophages which can lead to disturbances in the hematology profile and even death. As part of the condition profile, there have been reports proving a massive overexpression of interferon-gamma which is thought to drive the immune hyperactivation leading to organ failure.[A38676] This condition is usually developed and present the symptomatic profile within the first months or years of life. These symptoms consist of fever, enlarged liver or spleen and a lower number of blood cells.[L4840] | In phase 2/3 clinical trials, emapalumab administered concomitantly with dexamethasone reported an overall response in 63% of the patients. The overall response was defined as achievement of a complete or partial response or HLH improvement.[L4841] In this trial and as a proof of interferon-gamma neutralization, there was registered a sharp decrease in serum CXCL9 and to avoid QT prolongation in the presence of low doses of emapalumab.[L4846] | Emapalumab acts by binding and neutralizing interferon-gamma.[A38676] The specific interaction between emapalumab and interferon-gamma produces an inhibition in the interaction between interferon-gamma and its cognate receptor on T-cells which produces the neutralizing activity.[L4845] It is important to consider that emapalumab inhibits both free and IFNGR1-bound interferon-gamma as well as the interaction with IFNGR1 and IFNGR2 at the cell surface.[A40061] HLH is an immune dysregulation syndrome in which several cytokines are involved but it has been reported that interferon-gamma plays a pivotal role in the development of this disease as studies have shown a vast increase in the interferon-gamma levels in HLH patients.[A40059] | There are no reported effects in male or female reproductive organs after an 8- or 13-week repeat-dose toxicity study in animals.[FDA label] | Monoclonal antibodies are thought to be internalized in endothelial cells bound to Fc receptor and rescued from metabolism by recycling. Later, they are degraded in the reticuloendothelial system to small peptides and amino acids which can be used for de-novo protein synthesis.[A31470] | In clinical pharmacokinetic studies, a dose of 1 mg/kg of emapalumab was administered which generated a peak concentration at steady state of 44 mcg/ml and a median steady-state concentration of 25 mcg/ml. The serum concentration of emapalumab increases proportionally between a dose of 1-3 mg/kg and the steady-state is attained by the 7th infusion.[FDA label] | The central and peripheral volume of distribution of emapalumab are 4.2 and 5.6 L, respectively.[FDA label] | Emapalumab clearance is reported to be 0.007 L/h in healthy subjects. This clearance rate can vary in HLH patients depending on the production of interferon-gamma.[FDA label] | Globulins | NA | NA | NA | NA | Interferon gamma | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 15590 | Th1610 | Emapalumab | >Th1610_Emapalumab EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKDGSSGWYVPHWFDPWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | 154400 | C6430H9898N1718O2038S46 | 6.6 - 7.2 | NA | 78 ºC | Emapalumab elimination half-life is of approximately 22 days in healthy subjects and it ranges between 2.5-18.9 in HLH patients.[FDA label] | Emapalumab, also known as NI-0501, is a fully human monoclonal antibody that targets interferon gamma. Emapalumab development was sponsored by NovImmune SA, further developed by Sobi and FDA approved on November 20, 2018.[A38676, L4840] The approval of emapalumab was followed by the designation of orphan drug, priority review and breakthrough therapy.[L4840] As well, emapalumab was given the status of PRIME by the EMA.[L4845] | Emapalumab is indicated for the treatment of pediatric and adult patients with primary hemophagocytic lymphohistiocytosis (HLH) with refractory, recurrent or progressive disease or intolerance to conventional HLH therapy.[L4840] The HLH condition is a hyperinflammatory status characterized by the overwhelming activation of normal T lymphocytes and macrophages which can lead to disturbances in the hematology profile and even death. As part of the condition profile, there have been reports proving a massive overexpression of interferon-gamma which is thought to drive the immune hyperactivation leading to organ failure.[A38676] This condition is usually developed and present the symptomatic profile within the first months or years of life. These symptoms consist of fever, enlarged liver or spleen and a lower number of blood cells.[L4840] | In phase 2/3 clinical trials, emapalumab administered concomitantly with dexamethasone reported an overall response in 63% of the patients. The overall response was defined as achievement of a complete or partial response or HLH improvement.[L4841] In this trial and as a proof of interferon-gamma neutralization, there was registered a sharp decrease in serum CXCL9 and to avoid QT prolongation in the presence of low doses of emapalumab.[L4846] | Emapalumab acts by binding and neutralizing interferon-gamma.[A38676] The specific interaction between emapalumab and interferon-gamma produces an inhibition in the interaction between interferon-gamma and its cognate receptor on T-cells which produces the neutralizing activity.[L4845] It is important to consider that emapalumab inhibits both free and IFNGR1-bound interferon-gamma as well as the interaction with IFNGR1 and IFNGR2 at the cell surface.[A40061] HLH is an immune dysregulation syndrome in which several cytokines are involved but it has been reported that interferon-gamma plays a pivotal role in the development of this disease as studies have shown a vast increase in the interferon-gamma levels in HLH patients.[A40059] | There are no reported effects in male or female reproductive organs after an 8- or 13-week repeat-dose toxicity study in animals.[FDA label] | Monoclonal antibodies are thought to be internalized in endothelial cells bound to Fc receptor and rescued from metabolism by recycling. Later, they are degraded in the reticuloendothelial system to small peptides and amino acids which can be used for de-novo protein synthesis.[A31470] | In clinical pharmacokinetic studies, a dose of 1 mg/kg of emapalumab was administered which generated a peak concentration at steady state of 44 mcg/ml and a median steady-state concentration of 25 mcg/ml. The serum concentration of emapalumab increases proportionally between a dose of 1-3 mg/kg and the steady-state is attained by the 7th infusion.[FDA label] | The central and peripheral volume of distribution of emapalumab are 4.2 and 5.6 L, respectively.[FDA label] | Emapalumab clearance is reported to be 0.007 L/h in healthy subjects. This clearance rate can vary in HLH patients depending on the production of interferon-gamma.[FDA label] | Immunoglobulins | NA | NA | NA | NA | Interferon gamma | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 15591 | Th1610 | Emapalumab | >Th1610_Emapalumab EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKDGSSGWYVPHWFDPWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | 154400 | C6430H9898N1718O2038S46 | 6.6 - 7.2 | NA | 78 ºC | Emapalumab elimination half-life is of approximately 22 days in healthy subjects and it ranges between 2.5-18.9 in HLH patients.[FDA label] | Emapalumab, also known as NI-0501, is a fully human monoclonal antibody that targets interferon gamma. Emapalumab development was sponsored by NovImmune SA, further developed by Sobi and FDA approved on November 20, 2018.[A38676, L4840] The approval of emapalumab was followed by the designation of orphan drug, priority review and breakthrough therapy.[L4840] As well, emapalumab was given the status of PRIME by the EMA.[L4845] | Emapalumab is indicated for the treatment of pediatric and adult patients with primary hemophagocytic lymphohistiocytosis (HLH) with refractory, recurrent or progressive disease or intolerance to conventional HLH therapy.[L4840] The HLH condition is a hyperinflammatory status characterized by the overwhelming activation of normal T lymphocytes and macrophages which can lead to disturbances in the hematology profile and even death. As part of the condition profile, there have been reports proving a massive overexpression of interferon-gamma which is thought to drive the immune hyperactivation leading to organ failure.[A38676] This condition is usually developed and present the symptomatic profile within the first months or years of life. These symptoms consist of fever, enlarged liver or spleen and a lower number of blood cells.[L4840] | In phase 2/3 clinical trials, emapalumab administered concomitantly with dexamethasone reported an overall response in 63% of the patients. The overall response was defined as achievement of a complete or partial response or HLH improvement.[L4841] In this trial and as a proof of interferon-gamma neutralization, there was registered a sharp decrease in serum CXCL9 and to avoid QT prolongation in the presence of low doses of emapalumab.[L4846] | Emapalumab acts by binding and neutralizing interferon-gamma.[A38676] The specific interaction between emapalumab and interferon-gamma produces an inhibition in the interaction between interferon-gamma and its cognate receptor on T-cells which produces the neutralizing activity.[L4845] It is important to consider that emapalumab inhibits both free and IFNGR1-bound interferon-gamma as well as the interaction with IFNGR1 and IFNGR2 at the cell surface.[A40061] HLH is an immune dysregulation syndrome in which several cytokines are involved but it has been reported that interferon-gamma plays a pivotal role in the development of this disease as studies have shown a vast increase in the interferon-gamma levels in HLH patients.[A40059] | There are no reported effects in male or female reproductive organs after an 8- or 13-week repeat-dose toxicity study in animals.[FDA label] | Monoclonal antibodies are thought to be internalized in endothelial cells bound to Fc receptor and rescued from metabolism by recycling. Later, they are degraded in the reticuloendothelial system to small peptides and amino acids which can be used for de-novo protein synthesis.[A31470] | In clinical pharmacokinetic studies, a dose of 1 mg/kg of emapalumab was administered which generated a peak concentration at steady state of 44 mcg/ml and a median steady-state concentration of 25 mcg/ml. The serum concentration of emapalumab increases proportionally between a dose of 1-3 mg/kg and the steady-state is attained by the 7th infusion.[FDA label] | The central and peripheral volume of distribution of emapalumab are 4.2 and 5.6 L, respectively.[FDA label] | Emapalumab clearance is reported to be 0.007 L/h in healthy subjects. This clearance rate can vary in HLH patients depending on the production of interferon-gamma.[FDA label] | Immunoproteins | NA | NA | NA | NA | Interferon gamma | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 15592 | Th1610 | Emapalumab | >Th1610_Emapalumab EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKDGSSGWYVPHWFDPWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | 154400 | C6430H9898N1718O2038S46 | 6.6 - 7.2 | NA | 78 ºC | Emapalumab elimination half-life is of approximately 22 days in healthy subjects and it ranges between 2.5-18.9 in HLH patients.[FDA label] | Emapalumab, also known as NI-0501, is a fully human monoclonal antibody that targets interferon gamma. Emapalumab development was sponsored by NovImmune SA, further developed by Sobi and FDA approved on November 20, 2018.[A38676, L4840] The approval of emapalumab was followed by the designation of orphan drug, priority review and breakthrough therapy.[L4840] As well, emapalumab was given the status of PRIME by the EMA.[L4845] | Emapalumab is indicated for the treatment of pediatric and adult patients with primary hemophagocytic lymphohistiocytosis (HLH) with refractory, recurrent or progressive disease or intolerance to conventional HLH therapy.[L4840] The HLH condition is a hyperinflammatory status characterized by the overwhelming activation of normal T lymphocytes and macrophages which can lead to disturbances in the hematology profile and even death. As part of the condition profile, there have been reports proving a massive overexpression of interferon-gamma which is thought to drive the immune hyperactivation leading to organ failure.[A38676] This condition is usually developed and present the symptomatic profile within the first months or years of life. These symptoms consist of fever, enlarged liver or spleen and a lower number of blood cells.[L4840] | In phase 2/3 clinical trials, emapalumab administered concomitantly with dexamethasone reported an overall response in 63% of the patients. The overall response was defined as achievement of a complete or partial response or HLH improvement.[L4841] In this trial and as a proof of interferon-gamma neutralization, there was registered a sharp decrease in serum CXCL9 and to avoid QT prolongation in the presence of low doses of emapalumab.[L4846] | Emapalumab acts by binding and neutralizing interferon-gamma.[A38676] The specific interaction between emapalumab and interferon-gamma produces an inhibition in the interaction between interferon-gamma and its cognate receptor on T-cells which produces the neutralizing activity.[L4845] It is important to consider that emapalumab inhibits both free and IFNGR1-bound interferon-gamma as well as the interaction with IFNGR1 and IFNGR2 at the cell surface.[A40061] HLH is an immune dysregulation syndrome in which several cytokines are involved but it has been reported that interferon-gamma plays a pivotal role in the development of this disease as studies have shown a vast increase in the interferon-gamma levels in HLH patients.[A40059] | There are no reported effects in male or female reproductive organs after an 8- or 13-week repeat-dose toxicity study in animals.[FDA label] | Monoclonal antibodies are thought to be internalized in endothelial cells bound to Fc receptor and rescued from metabolism by recycling. Later, they are degraded in the reticuloendothelial system to small peptides and amino acids which can be used for de-novo protein synthesis.[A31470] | In clinical pharmacokinetic studies, a dose of 1 mg/kg of emapalumab was administered which generated a peak concentration at steady state of 44 mcg/ml and a median steady-state concentration of 25 mcg/ml. The serum concentration of emapalumab increases proportionally between a dose of 1-3 mg/kg and the steady-state is attained by the 7th infusion.[FDA label] | The central and peripheral volume of distribution of emapalumab are 4.2 and 5.6 L, respectively.[FDA label] | Emapalumab clearance is reported to be 0.007 L/h in healthy subjects. This clearance rate can vary in HLH patients depending on the production of interferon-gamma.[FDA label] | Immunosuppressive Agents | NA | NA | NA | NA | Interferon gamma | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 15593 | Th1610 | Emapalumab | >Th1610_Emapalumab EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKDGSSGWYVPHWFDPWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | 154400 | C6430H9898N1718O2038S46 | 6.6 - 7.2 | NA | 78 ºC | Emapalumab elimination half-life is of approximately 22 days in healthy subjects and it ranges between 2.5-18.9 in HLH patients.[FDA label] | Emapalumab, also known as NI-0501, is a fully human monoclonal antibody that targets interferon gamma. Emapalumab development was sponsored by NovImmune SA, further developed by Sobi and FDA approved on November 20, 2018.[A38676, L4840] The approval of emapalumab was followed by the designation of orphan drug, priority review and breakthrough therapy.[L4840] As well, emapalumab was given the status of PRIME by the EMA.[L4845] | Emapalumab is indicated for the treatment of pediatric and adult patients with primary hemophagocytic lymphohistiocytosis (HLH) with refractory, recurrent or progressive disease or intolerance to conventional HLH therapy.[L4840] The HLH condition is a hyperinflammatory status characterized by the overwhelming activation of normal T lymphocytes and macrophages which can lead to disturbances in the hematology profile and even death. As part of the condition profile, there have been reports proving a massive overexpression of interferon-gamma which is thought to drive the immune hyperactivation leading to organ failure.[A38676] This condition is usually developed and present the symptomatic profile within the first months or years of life. These symptoms consist of fever, enlarged liver or spleen and a lower number of blood cells.[L4840] | In phase 2/3 clinical trials, emapalumab administered concomitantly with dexamethasone reported an overall response in 63% of the patients. The overall response was defined as achievement of a complete or partial response or HLH improvement.[L4841] In this trial and as a proof of interferon-gamma neutralization, there was registered a sharp decrease in serum CXCL9 and to avoid QT prolongation in the presence of low doses of emapalumab.[L4846] | Emapalumab acts by binding and neutralizing interferon-gamma.[A38676] The specific interaction between emapalumab and interferon-gamma produces an inhibition in the interaction between interferon-gamma and its cognate receptor on T-cells which produces the neutralizing activity.[L4845] It is important to consider that emapalumab inhibits both free and IFNGR1-bound interferon-gamma as well as the interaction with IFNGR1 and IFNGR2 at the cell surface.[A40061] HLH is an immune dysregulation syndrome in which several cytokines are involved but it has been reported that interferon-gamma plays a pivotal role in the development of this disease as studies have shown a vast increase in the interferon-gamma levels in HLH patients.[A40059] | There are no reported effects in male or female reproductive organs after an 8- or 13-week repeat-dose toxicity study in animals.[FDA label] | Monoclonal antibodies are thought to be internalized in endothelial cells bound to Fc receptor and rescued from metabolism by recycling. Later, they are degraded in the reticuloendothelial system to small peptides and amino acids which can be used for de-novo protein synthesis.[A31470] | In clinical pharmacokinetic studies, a dose of 1 mg/kg of emapalumab was administered which generated a peak concentration at steady state of 44 mcg/ml and a median steady-state concentration of 25 mcg/ml. The serum concentration of emapalumab increases proportionally between a dose of 1-3 mg/kg and the steady-state is attained by the 7th infusion.[FDA label] | The central and peripheral volume of distribution of emapalumab are 4.2 and 5.6 L, respectively.[FDA label] | Emapalumab clearance is reported to be 0.007 L/h in healthy subjects. This clearance rate can vary in HLH patients depending on the production of interferon-gamma.[FDA label] | Interferon gamma Antagonists | NA | NA | NA | NA | Interferon gamma | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 15594 | Th1610 | Emapalumab | >Th1610_Emapalumab EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKDGSSGWYVPHWFDPWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | 154400 | C6430H9898N1718O2038S46 | 6.6 - 7.2 | NA | 78 ºC | Emapalumab elimination half-life is of approximately 22 days in healthy subjects and it ranges between 2.5-18.9 in HLH patients.[FDA label] | Emapalumab, also known as NI-0501, is a fully human monoclonal antibody that targets interferon gamma. Emapalumab development was sponsored by NovImmune SA, further developed by Sobi and FDA approved on November 20, 2018.[A38676, L4840] The approval of emapalumab was followed by the designation of orphan drug, priority review and breakthrough therapy.[L4840] As well, emapalumab was given the status of PRIME by the EMA.[L4845] | Emapalumab is indicated for the treatment of pediatric and adult patients with primary hemophagocytic lymphohistiocytosis (HLH) with refractory, recurrent or progressive disease or intolerance to conventional HLH therapy.[L4840] The HLH condition is a hyperinflammatory status characterized by the overwhelming activation of normal T lymphocytes and macrophages which can lead to disturbances in the hematology profile and even death. As part of the condition profile, there have been reports proving a massive overexpression of interferon-gamma which is thought to drive the immune hyperactivation leading to organ failure.[A38676] This condition is usually developed and present the symptomatic profile within the first months or years of life. These symptoms consist of fever, enlarged liver or spleen and a lower number of blood cells.[L4840] | In phase 2/3 clinical trials, emapalumab administered concomitantly with dexamethasone reported an overall response in 63% of the patients. The overall response was defined as achievement of a complete or partial response or HLH improvement.[L4841] In this trial and as a proof of interferon-gamma neutralization, there was registered a sharp decrease in serum CXCL9 and to avoid QT prolongation in the presence of low doses of emapalumab.[L4846] | Emapalumab acts by binding and neutralizing interferon-gamma.[A38676] The specific interaction between emapalumab and interferon-gamma produces an inhibition in the interaction between interferon-gamma and its cognate receptor on T-cells which produces the neutralizing activity.[L4845] It is important to consider that emapalumab inhibits both free and IFNGR1-bound interferon-gamma as well as the interaction with IFNGR1 and IFNGR2 at the cell surface.[A40061] HLH is an immune dysregulation syndrome in which several cytokines are involved but it has been reported that interferon-gamma plays a pivotal role in the development of this disease as studies have shown a vast increase in the interferon-gamma levels in HLH patients.[A40059] | There are no reported effects in male or female reproductive organs after an 8- or 13-week repeat-dose toxicity study in animals.[FDA label] | Monoclonal antibodies are thought to be internalized in endothelial cells bound to Fc receptor and rescued from metabolism by recycling. Later, they are degraded in the reticuloendothelial system to small peptides and amino acids which can be used for de-novo protein synthesis.[A31470] | In clinical pharmacokinetic studies, a dose of 1 mg/kg of emapalumab was administered which generated a peak concentration at steady state of 44 mcg/ml and a median steady-state concentration of 25 mcg/ml. The serum concentration of emapalumab increases proportionally between a dose of 1-3 mg/kg and the steady-state is attained by the 7th infusion.[FDA label] | The central and peripheral volume of distribution of emapalumab are 4.2 and 5.6 L, respectively.[FDA label] | Emapalumab clearance is reported to be 0.007 L/h in healthy subjects. This clearance rate can vary in HLH patients depending on the production of interferon-gamma.[FDA label] | Interferon gamma Blocker | NA | NA | NA | NA | Interferon gamma | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 15595 | Th1610 | Emapalumab | >Th1610_Emapalumab EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKDGSSGWYVPHWFDPWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | 154400 | C6430H9898N1718O2038S46 | 6.6 - 7.2 | NA | 78 ºC | Emapalumab elimination half-life is of approximately 22 days in healthy subjects and it ranges between 2.5-18.9 in HLH patients.[FDA label] | Emapalumab, also known as NI-0501, is a fully human monoclonal antibody that targets interferon gamma. Emapalumab development was sponsored by NovImmune SA, further developed by Sobi and FDA approved on November 20, 2018.[A38676, L4840] The approval of emapalumab was followed by the designation of orphan drug, priority review and breakthrough therapy.[L4840] As well, emapalumab was given the status of PRIME by the EMA.[L4845] | Emapalumab is indicated for the treatment of pediatric and adult patients with primary hemophagocytic lymphohistiocytosis (HLH) with refractory, recurrent or progressive disease or intolerance to conventional HLH therapy.[L4840] The HLH condition is a hyperinflammatory status characterized by the overwhelming activation of normal T lymphocytes and macrophages which can lead to disturbances in the hematology profile and even death. As part of the condition profile, there have been reports proving a massive overexpression of interferon-gamma which is thought to drive the immune hyperactivation leading to organ failure.[A38676] This condition is usually developed and present the symptomatic profile within the first months or years of life. These symptoms consist of fever, enlarged liver or spleen and a lower number of blood cells.[L4840] | In phase 2/3 clinical trials, emapalumab administered concomitantly with dexamethasone reported an overall response in 63% of the patients. The overall response was defined as achievement of a complete or partial response or HLH improvement.[L4841] In this trial and as a proof of interferon-gamma neutralization, there was registered a sharp decrease in serum CXCL9 and to avoid QT prolongation in the presence of low doses of emapalumab.[L4846] | Emapalumab acts by binding and neutralizing interferon-gamma.[A38676] The specific interaction between emapalumab and interferon-gamma produces an inhibition in the interaction between interferon-gamma and its cognate receptor on T-cells which produces the neutralizing activity.[L4845] It is important to consider that emapalumab inhibits both free and IFNGR1-bound interferon-gamma as well as the interaction with IFNGR1 and IFNGR2 at the cell surface.[A40061] HLH is an immune dysregulation syndrome in which several cytokines are involved but it has been reported that interferon-gamma plays a pivotal role in the development of this disease as studies have shown a vast increase in the interferon-gamma levels in HLH patients.[A40059] | There are no reported effects in male or female reproductive organs after an 8- or 13-week repeat-dose toxicity study in animals.[FDA label] | Monoclonal antibodies are thought to be internalized in endothelial cells bound to Fc receptor and rescued from metabolism by recycling. Later, they are degraded in the reticuloendothelial system to small peptides and amino acids which can be used for de-novo protein synthesis.[A31470] | In clinical pharmacokinetic studies, a dose of 1 mg/kg of emapalumab was administered which generated a peak concentration at steady state of 44 mcg/ml and a median steady-state concentration of 25 mcg/ml. The serum concentration of emapalumab increases proportionally between a dose of 1-3 mg/kg and the steady-state is attained by the 7th infusion.[FDA label] | The central and peripheral volume of distribution of emapalumab are 4.2 and 5.6 L, respectively.[FDA label] | Emapalumab clearance is reported to be 0.007 L/h in healthy subjects. This clearance rate can vary in HLH patients depending on the production of interferon-gamma.[FDA label] | Interferon-gamma | NA | NA | NA | NA | Interferon gamma | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 15596 | Th1610 | Emapalumab | >Th1610_Emapalumab EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKDGSSGWYVPHWFDPWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | 154400 | C6430H9898N1718O2038S46 | 6.6 - 7.2 | NA | 78 ºC | Emapalumab elimination half-life is of approximately 22 days in healthy subjects and it ranges between 2.5-18.9 in HLH patients.[FDA label] | Emapalumab, also known as NI-0501, is a fully human monoclonal antibody that targets interferon gamma. Emapalumab development was sponsored by NovImmune SA, further developed by Sobi and FDA approved on November 20, 2018.[A38676, L4840] The approval of emapalumab was followed by the designation of orphan drug, priority review and breakthrough therapy.[L4840] As well, emapalumab was given the status of PRIME by the EMA.[L4845] | Emapalumab is indicated for the treatment of pediatric and adult patients with primary hemophagocytic lymphohistiocytosis (HLH) with refractory, recurrent or progressive disease or intolerance to conventional HLH therapy.[L4840] The HLH condition is a hyperinflammatory status characterized by the overwhelming activation of normal T lymphocytes and macrophages which can lead to disturbances in the hematology profile and even death. As part of the condition profile, there have been reports proving a massive overexpression of interferon-gamma which is thought to drive the immune hyperactivation leading to organ failure.[A38676] This condition is usually developed and present the symptomatic profile within the first months or years of life. These symptoms consist of fever, enlarged liver or spleen and a lower number of blood cells.[L4840] | In phase 2/3 clinical trials, emapalumab administered concomitantly with dexamethasone reported an overall response in 63% of the patients. The overall response was defined as achievement of a complete or partial response or HLH improvement.[L4841] In this trial and as a proof of interferon-gamma neutralization, there was registered a sharp decrease in serum CXCL9 and to avoid QT prolongation in the presence of low doses of emapalumab.[L4846] | Emapalumab acts by binding and neutralizing interferon-gamma.[A38676] The specific interaction between emapalumab and interferon-gamma produces an inhibition in the interaction between interferon-gamma and its cognate receptor on T-cells which produces the neutralizing activity.[L4845] It is important to consider that emapalumab inhibits both free and IFNGR1-bound interferon-gamma as well as the interaction with IFNGR1 and IFNGR2 at the cell surface.[A40061] HLH is an immune dysregulation syndrome in which several cytokines are involved but it has been reported that interferon-gamma plays a pivotal role in the development of this disease as studies have shown a vast increase in the interferon-gamma levels in HLH patients.[A40059] | There are no reported effects in male or female reproductive organs after an 8- or 13-week repeat-dose toxicity study in animals.[FDA label] | Monoclonal antibodies are thought to be internalized in endothelial cells bound to Fc receptor and rescued from metabolism by recycling. Later, they are degraded in the reticuloendothelial system to small peptides and amino acids which can be used for de-novo protein synthesis.[A31470] | In clinical pharmacokinetic studies, a dose of 1 mg/kg of emapalumab was administered which generated a peak concentration at steady state of 44 mcg/ml and a median steady-state concentration of 25 mcg/ml. The serum concentration of emapalumab increases proportionally between a dose of 1-3 mg/kg and the steady-state is attained by the 7th infusion.[FDA label] | The central and peripheral volume of distribution of emapalumab are 4.2 and 5.6 L, respectively.[FDA label] | Emapalumab clearance is reported to be 0.007 L/h in healthy subjects. This clearance rate can vary in HLH patients depending on the production of interferon-gamma.[FDA label] | Proteins | NA | NA | NA | NA | Interferon gamma | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 15597 | Th1610 | Emapalumab | >Th1610_Emapalumab EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKDGSSGWYVPHWFDPWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | 154400 | C6430H9898N1718O2038S46 | 6.6 - 7.2 | NA | 78 ºC | Emapalumab elimination half-life is of approximately 22 days in healthy subjects and it ranges between 2.5-18.9 in HLH patients.[FDA label] | Emapalumab, also known as NI-0501, is a fully human monoclonal antibody that targets interferon gamma. Emapalumab development was sponsored by NovImmune SA, further developed by Sobi and FDA approved on November 20, 2018.[A38676, L4840] The approval of emapalumab was followed by the designation of orphan drug, priority review and breakthrough therapy.[L4840] As well, emapalumab was given the status of PRIME by the EMA.[L4845] | Emapalumab is indicated for the treatment of pediatric and adult patients with primary hemophagocytic lymphohistiocytosis (HLH) with refractory, recurrent or progressive disease or intolerance to conventional HLH therapy.[L4840] The HLH condition is a hyperinflammatory status characterized by the overwhelming activation of normal T lymphocytes and macrophages which can lead to disturbances in the hematology profile and even death. As part of the condition profile, there have been reports proving a massive overexpression of interferon-gamma which is thought to drive the immune hyperactivation leading to organ failure.[A38676] This condition is usually developed and present the symptomatic profile within the first months or years of life. These symptoms consist of fever, enlarged liver or spleen and a lower number of blood cells.[L4840] | In phase 2/3 clinical trials, emapalumab administered concomitantly with dexamethasone reported an overall response in 63% of the patients. The overall response was defined as achievement of a complete or partial response or HLH improvement.[L4841] In this trial and as a proof of interferon-gamma neutralization, there was registered a sharp decrease in serum CXCL9 and to avoid QT prolongation in the presence of low doses of emapalumab.[L4846] | Emapalumab acts by binding and neutralizing interferon-gamma.[A38676] The specific interaction between emapalumab and interferon-gamma produces an inhibition in the interaction between interferon-gamma and its cognate receptor on T-cells which produces the neutralizing activity.[L4845] It is important to consider that emapalumab inhibits both free and IFNGR1-bound interferon-gamma as well as the interaction with IFNGR1 and IFNGR2 at the cell surface.[A40061] HLH is an immune dysregulation syndrome in which several cytokines are involved but it has been reported that interferon-gamma plays a pivotal role in the development of this disease as studies have shown a vast increase in the interferon-gamma levels in HLH patients.[A40059] | There are no reported effects in male or female reproductive organs after an 8- or 13-week repeat-dose toxicity study in animals.[FDA label] | Monoclonal antibodies are thought to be internalized in endothelial cells bound to Fc receptor and rescued from metabolism by recycling. Later, they are degraded in the reticuloendothelial system to small peptides and amino acids which can be used for de-novo protein synthesis.[A31470] | In clinical pharmacokinetic studies, a dose of 1 mg/kg of emapalumab was administered which generated a peak concentration at steady state of 44 mcg/ml and a median steady-state concentration of 25 mcg/ml. The serum concentration of emapalumab increases proportionally between a dose of 1-3 mg/kg and the steady-state is attained by the 7th infusion.[FDA label] | The central and peripheral volume of distribution of emapalumab are 4.2 and 5.6 L, respectively.[FDA label] | Emapalumab clearance is reported to be 0.007 L/h in healthy subjects. This clearance rate can vary in HLH patients depending on the production of interferon-gamma.[FDA label] | Selective Immunosuppressants | NA | NA | NA | NA | Interferon gamma | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 15598 | Th1610 | Emapalumab | >Th1610_Emapalumab EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKDGSSGWYVPHWFDPWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK | 154400 | C6430H9898N1718O2038S46 | 6.6 - 7.2 | NA | 78 ºC | Emapalumab elimination half-life is of approximately 22 days in healthy subjects and it ranges between 2.5-18.9 in HLH patients.[FDA label] | Emapalumab, also known as NI-0501, is a fully human monoclonal antibody that targets interferon gamma. Emapalumab development was sponsored by NovImmune SA, further developed by Sobi and FDA approved on November 20, 2018.[A38676, L4840] The approval of emapalumab was followed by the designation of orphan drug, priority review and breakthrough therapy.[L4840] As well, emapalumab was given the status of PRIME by the EMA.[L4845] | Emapalumab is indicated for the treatment of pediatric and adult patients with primary hemophagocytic lymphohistiocytosis (HLH) with refractory, recurrent or progressive disease or intolerance to conventional HLH therapy.[L4840] The HLH condition is a hyperinflammatory status characterized by the overwhelming activation of normal T lymphocytes and macrophages which can lead to disturbances in the hematology profile and even death. As part of the condition profile, there have been reports proving a massive overexpression of interferon-gamma which is thought to drive the immune hyperactivation leading to organ failure.[A38676] This condition is usually developed and present the symptomatic profile within the first months or years of life. These symptoms consist of fever, enlarged liver or spleen and a lower number of blood cells.[L4840] | In phase 2/3 clinical trials, emapalumab administered concomitantly with dexamethasone reported an overall response in 63% of the patients. The overall response was defined as achievement of a complete or partial response or HLH improvement.[L4841] In this trial and as a proof of interferon-gamma neutralization, there was registered a sharp decrease in serum CXCL9 and to avoid QT prolongation in the presence of low doses of emapalumab.[L4846] | Emapalumab acts by binding and neutralizing interferon-gamma.[A38676] The specific interaction between emapalumab and interferon-gamma produces an inhibition in the interaction between interferon-gamma and its cognate receptor on T-cells which produces the neutralizing activity.[L4845] It is important to consider that emapalumab inhibits both free and IFNGR1-bound interferon-gamma as well as the interaction with IFNGR1 and IFNGR2 at the cell surface.[A40061] HLH is an immune dysregulation syndrome in which several cytokines are involved but it has been reported that interferon-gamma plays a pivotal role in the development of this disease as studies have shown a vast increase in the interferon-gamma levels in HLH patients.[A40059] | There are no reported effects in male or female reproductive organs after an 8- or 13-week repeat-dose toxicity study in animals.[FDA label] | Monoclonal antibodies are thought to be internalized in endothelial cells bound to Fc receptor and rescued from metabolism by recycling. Later, they are degraded in the reticuloendothelial system to small peptides and amino acids which can be used for de-novo protein synthesis.[A31470] | In clinical pharmacokinetic studies, a dose of 1 mg/kg of emapalumab was administered which generated a peak concentration at steady state of 44 mcg/ml and a median steady-state concentration of 25 mcg/ml. The serum concentration of emapalumab increases proportionally between a dose of 1-3 mg/kg and the steady-state is attained by the 7th infusion.[FDA label] | The central and peripheral volume of distribution of emapalumab are 4.2 and 5.6 L, respectively.[FDA label] | Emapalumab clearance is reported to be 0.007 L/h in healthy subjects. This clearance rate can vary in HLH patients depending on the production of interferon-gamma.[FDA label] | Serum Globulins | NA | NA | NA | NA | Interferon gamma | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 15599 | Th1611 | Tagraxofusp | >Th1611_Tagraxofusp MGADDVVDSSKSFVMENFSSYHGTKPGYVDSIQKGIQKPKSGTQGNYDDDWKGFYSTDNKYDAAGYSVDNENPLSGKAGGVVKVTYPGLTKVLALKVDNAETIKKELGLSLTEPLMEQVGTEEFIKRFGDGASRVVLSLPFAEGSSSVEYINNWEQAKALSVELEINFETRGKRGQDAMYEYMAQACAGNRVRRSVGSSLSCINLDWDVIRDKTKTKIESLKEHGPIKNKMSESPNKTVSEEKAKQYLEEFHQTALEHPELSELKTVTGTNPVFAGANYAAWAVNVAQVIDSETADNLEKTTAALSILPGIGSVMGIADGAVHHNTEEIVAQSIALSSLMVAQAIPLVGELVDIGFAAYNFVESIINLFQVVHNSYNRPAYSPGHKTRPHMAPMTQTTSLKTSWVNCSNMIDEIITHLKQPPLPLLDFNNLNGEDQDILMENNLRRPNLEAFNRAVKSLQNASAIESILKNLLPCLPLATAAPTRHPIHIKDGDWNEFRRKLTFYLKTLENAQAQQTTLSLAIF | NA | C2553 H4026 N692 O798 S16 | NA | NA | NA | The reported half-life of tagraxofusp is of around 51 minutes.[L4897] | Tagraxofusp is an IL-3 conjugated truncated diphtheria toxin.[L4895] It is composed by the catalytic and translocation domains of diphtheria toxin fused via Met-His linker to a full-length human IL-3.[L4897, L4898] Tagraxofusp was developed by Stemline Therapeutics Inc and FDA approved on December 21, 2018, as the first therapy for blastic plasmacytoid dendritic cell neoplasm.[L4894] This drug achieved approval after being designated with the title of breakthrough therapy, priority review, and orphan drug status.[L4893] Tagraxofusp has been designated as an orphan drug in the EU since November 2015.[L4898] | Tagraxofusp is indicated for the treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN) in adults and pediatric patients over 2 years old. This treatment allows an alternative for the previous intense treatment which consisted of intensive chemotherapy followed by bone marrow transplantation.[L4893] BPDCN is a rare hematologic malignancy derived from plasmacytoid dendritic cells. It is characterized by the significantly increased expression of cells expressing CD4/CD56/CD123 and other markers restricted to plasmacytoid dendritic cells and a lack of expression of lymphoid, natural killer or myeloid lineage-associated antigens.[A40274] A key feature of the malignant cells is the overexpression of CD123, also known as interleukin-3 receptor, and the constant requirement of IL-3 for survival.[L4897] | In vitro studies showed that BPDCN blasts are ultrasensitive to tagraxofusp by presenting IC50 values in the femtomolar scale.[L4897] One of the main physiological changes of BPDCN is the presence of elevated interferon alpha and to produce an inflammatory response. In trials with tagraxofusp and following cell depletion, there was observed a significant reduction in the levels of interferon alpha and interleukin 6.[L4896] In clinical trials, tagraxofusp reported complete remission and complete remission with a skin abnormality not indicative of active disease in 54% of the treated patients.[L4893] | Tagraxofusp binds to cells expressing the IL-3 receptor and delivers in them the diphtheria toxin after binding. This is very useful as the malignant cells in BPDCN present a particularly high expression of IL-3 receptor (CD123+ pDC).[L4896] To be more specific, tagraxofusp gets internalized to the IL-3 receptor-expressing cell allowing for diphtheria toxin translocation to the cytosol and followed by the binding to ADP-ribosylation elongation factor 2 which is a key factor for protein translation. Once the protein synthesis is inhibited, the cell goes under a process of apoptosis.[L4895, L4897] As the apoptosis induction requires an active state of protein synthesis, tagraxofusp is not able to perform its apoptotic function in dormant cells.[L4897] | There haven't been analysis observing the carcinogenic, mutagenic potential nor the effect on fertility. However, in studies performed in cynomolgus monkeys at an overdose rate of 1.6 times the recommended dose, it was observed severe kidney tubular degeneration. Similar studies at the recommended dose reported the presence of degeneration and necrosis of choroid plexus in the brain were. This effect seems to be progressive even 3 weeks after therapy withdrawal.[FDA label] | For the metabolism, as tagraxofusp is a fusion protein, it is expected to get processed until small peptides and amino acids by the actions of proteases. | The reported Cmax in clinical trials was of around 23 ng/ml.[L4897] After a 15 min infusion of a dose of 12 mcg/kg the registered AUC and Cmax was 231 mcg.h/L and 162 mcg/L respectively.[FDA label] | In BPDCN patients, the reported volume of distribution is of 5.1 L.[FDA label] | The clearance of tagraxofusp was reported to fit a mono-exponential model.[L4897] The reported clearance rate is reported to be of 7.1 L/h.[FDA label] | Amino Acids, Peptides, and Proteins | NA | NA | NA | NA | Interleukin-3 receptor subunit alpha,ADP-ribosylation factor-like protein 2 | Elzonris | Stemline Therapeutics B.V. | Stemline Therapeutics B.V. | Intravenous | 1 mg/ml | None. | capillary leak syndrome, high or low blood pressure, nausea, fatigue, swelling of extremities, fever, weight gain, constipation, vomiting, diarrhea, chills, headache, dizziness, decreased appetite, back pain, pain in extremities, shortness of breath, cough, nosebleed, sore throat or mouth pain, insomnia, anxiety, confusion, fast heart rate, itching, small red or purple spots on the skin, or blood in the urine. | Elzonris is used to treat blastic plasmacytoid dendritic cell neoplasm, a rare blood and/or bone marrow cancer. Elzonris is for use in adults and children at least 2 years old. Elzonris may also be used for purposes not listed in this medication guide. | ELZONRIS is a CD123-directed cytotoxin for the treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN) in adults and in pediatric patients 2 years and older. | NA | NA | Link | Link | NA |
| 15600 | Th1611 | Tagraxofusp | >Th1611_Tagraxofusp MGADDVVDSSKSFVMENFSSYHGTKPGYVDSIQKGIQKPKSGTQGNYDDDWKGFYSTDNKYDAAGYSVDNENPLSGKAGGVVKVTYPGLTKVLALKVDNAETIKKELGLSLTEPLMEQVGTEEFIKRFGDGASRVVLSLPFAEGSSSVEYINNWEQAKALSVELEINFETRGKRGQDAMYEYMAQACAGNRVRRSVGSSLSCINLDWDVIRDKTKTKIESLKEHGPIKNKMSESPNKTVSEEKAKQYLEEFHQTALEHPELSELKTVTGTNPVFAGANYAAWAVNVAQVIDSETADNLEKTTAALSILPGIGSVMGIADGAVHHNTEEIVAQSIALSSLMVAQAIPLVGELVDIGFAAYNFVESIINLFQVVHNSYNRPAYSPGHKTRPHMAPMTQTTSLKTSWVNCSNMIDEIITHLKQPPLPLLDFNNLNGEDQDILMENNLRRPNLEAFNRAVKSLQNASAIESILKNLLPCLPLATAAPTRHPIHIKDGDWNEFRRKLTFYLKTLENAQAQQTTLSLAIF | NA | C2553 H4026 N692 O798 S16 | NA | NA | NA | The reported half-life of tagraxofusp is of around 51 minutes.[L4897] | Tagraxofusp is an IL-3 conjugated truncated diphtheria toxin.[L4895] It is composed by the catalytic and translocation domains of diphtheria toxin fused via Met-His linker to a full-length human IL-3.[L4897, L4898] Tagraxofusp was developed by Stemline Therapeutics Inc and FDA approved on December 21, 2018, as the first therapy for blastic plasmacytoid dendritic cell neoplasm.[L4894] This drug achieved approval after being designated with the title of breakthrough therapy, priority review, and orphan drug status.[L4893] Tagraxofusp has been designated as an orphan drug in the EU since November 2015.[L4898] | Tagraxofusp is indicated for the treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN) in adults and pediatric patients over 2 years old. This treatment allows an alternative for the previous intense treatment which consisted of intensive chemotherapy followed by bone marrow transplantation.[L4893] BPDCN is a rare hematologic malignancy derived from plasmacytoid dendritic cells. It is characterized by the significantly increased expression of cells expressing CD4/CD56/CD123 and other markers restricted to plasmacytoid dendritic cells and a lack of expression of lymphoid, natural killer or myeloid lineage-associated antigens.[A40274] A key feature of the malignant cells is the overexpression of CD123, also known as interleukin-3 receptor, and the constant requirement of IL-3 for survival.[L4897] | In vitro studies showed that BPDCN blasts are ultrasensitive to tagraxofusp by presenting IC50 values in the femtomolar scale.[L4897] One of the main physiological changes of BPDCN is the presence of elevated interferon alpha and to produce an inflammatory response. In trials with tagraxofusp and following cell depletion, there was observed a significant reduction in the levels of interferon alpha and interleukin 6.[L4896] In clinical trials, tagraxofusp reported complete remission and complete remission with a skin abnormality not indicative of active disease in 54% of the treated patients.[L4893] | Tagraxofusp binds to cells expressing the IL-3 receptor and delivers in them the diphtheria toxin after binding. This is very useful as the malignant cells in BPDCN present a particularly high expression of IL-3 receptor (CD123+ pDC).[L4896] To be more specific, tagraxofusp gets internalized to the IL-3 receptor-expressing cell allowing for diphtheria toxin translocation to the cytosol and followed by the binding to ADP-ribosylation elongation factor 2 which is a key factor for protein translation. Once the protein synthesis is inhibited, the cell goes under a process of apoptosis.[L4895, L4897] As the apoptosis induction requires an active state of protein synthesis, tagraxofusp is not able to perform its apoptotic function in dormant cells.[L4897] | There haven't been analysis observing the carcinogenic, mutagenic potential nor the effect on fertility. However, in studies performed in cynomolgus monkeys at an overdose rate of 1.6 times the recommended dose, it was observed severe kidney tubular degeneration. Similar studies at the recommended dose reported the presence of degeneration and necrosis of choroid plexus in the brain were. This effect seems to be progressive even 3 weeks after therapy withdrawal.[FDA label] | For the metabolism, as tagraxofusp is a fusion protein, it is expected to get processed until small peptides and amino acids by the actions of proteases. | The reported Cmax in clinical trials was of around 23 ng/ml.[L4897] After a 15 min infusion of a dose of 12 mcg/kg the registered AUC and Cmax was 231 mcg.h/L and 162 mcg/L respectively.[FDA label] | In BPDCN patients, the reported volume of distribution is of 5.1 L.[FDA label] | The clearance of tagraxofusp was reported to fit a mono-exponential model.[L4897] The reported clearance rate is reported to be of 7.1 L/h.[FDA label] | Antineoplastic Agents | NA | NA | NA | NA | Interleukin-3 receptor subunit alpha,ADP-ribosylation factor-like protein 2 | Elzonris | Stemline Therapeutics, Inc. | Stemline Therapeutics, Inc. | Intravenous | 1000 ug/1mL | None. | capillary leak syndrome, high or low blood pressure, nausea, fatigue, swelling of extremities, fever, weight gain, constipation, vomiting, diarrhea, chills, headache, dizziness, decreased appetite, back pain, pain in extremities, shortness of breath, cough, nosebleed, sore throat or mouth pain, insomnia, anxiety, confusion, fast heart rate, itching, small red or purple spots on the skin, or blood in the urine. | Elzonris is used to treat blastic plasmacytoid dendritic cell neoplasm, a rare blood and/or bone marrow cancer. Elzonris is for use in adults and children at least 2 years old. Elzonris may also be used for purposes not listed in this medication guide. | ELZONRIS is a CD123-directed cytotoxin for the treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN) in adults and in pediatric patients 2 years and older. | NA | NA | Link | Link | NA |
| 15601 | Th1611 | Tagraxofusp | >Th1611_Tagraxofusp MGADDVVDSSKSFVMENFSSYHGTKPGYVDSIQKGIQKPKSGTQGNYDDDWKGFYSTDNKYDAAGYSVDNENPLSGKAGGVVKVTYPGLTKVLALKVDNAETIKKELGLSLTEPLMEQVGTEEFIKRFGDGASRVVLSLPFAEGSSSVEYINNWEQAKALSVELEINFETRGKRGQDAMYEYMAQACAGNRVRRSVGSSLSCINLDWDVIRDKTKTKIESLKEHGPIKNKMSESPNKTVSEEKAKQYLEEFHQTALEHPELSELKTVTGTNPVFAGANYAAWAVNVAQVIDSETADNLEKTTAALSILPGIGSVMGIADGAVHHNTEEIVAQSIALSSLMVAQAIPLVGELVDIGFAAYNFVESIINLFQVVHNSYNRPAYSPGHKTRPHMAPMTQTTSLKTSWVNCSNMIDEIITHLKQPPLPLLDFNNLNGEDQDILMENNLRRPNLEAFNRAVKSLQNASAIESILKNLLPCLPLATAAPTRHPIHIKDGDWNEFRRKLTFYLKTLENAQAQQTTLSLAIF | NA | C2553 H4026 N692 O798 S16 | NA | NA | NA | The reported half-life of tagraxofusp is of around 51 minutes.[L4897] | Tagraxofusp is an IL-3 conjugated truncated diphtheria toxin.[L4895] It is composed by the catalytic and translocation domains of diphtheria toxin fused via Met-His linker to a full-length human IL-3.[L4897, L4898] Tagraxofusp was developed by Stemline Therapeutics Inc and FDA approved on December 21, 2018, as the first therapy for blastic plasmacytoid dendritic cell neoplasm.[L4894] This drug achieved approval after being designated with the title of breakthrough therapy, priority review, and orphan drug status.[L4893] Tagraxofusp has been designated as an orphan drug in the EU since November 2015.[L4898] | Tagraxofusp is indicated for the treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN) in adults and pediatric patients over 2 years old. This treatment allows an alternative for the previous intense treatment which consisted of intensive chemotherapy followed by bone marrow transplantation.[L4893] BPDCN is a rare hematologic malignancy derived from plasmacytoid dendritic cells. It is characterized by the significantly increased expression of cells expressing CD4/CD56/CD123 and other markers restricted to plasmacytoid dendritic cells and a lack of expression of lymphoid, natural killer or myeloid lineage-associated antigens.[A40274] A key feature of the malignant cells is the overexpression of CD123, also known as interleukin-3 receptor, and the constant requirement of IL-3 for survival.[L4897] | In vitro studies showed that BPDCN blasts are ultrasensitive to tagraxofusp by presenting IC50 values in the femtomolar scale.[L4897] One of the main physiological changes of BPDCN is the presence of elevated interferon alpha and to produce an inflammatory response. In trials with tagraxofusp and following cell depletion, there was observed a significant reduction in the levels of interferon alpha and interleukin 6.[L4896] In clinical trials, tagraxofusp reported complete remission and complete remission with a skin abnormality not indicative of active disease in 54% of the treated patients.[L4893] | Tagraxofusp binds to cells expressing the IL-3 receptor and delivers in them the diphtheria toxin after binding. This is very useful as the malignant cells in BPDCN present a particularly high expression of IL-3 receptor (CD123+ pDC).[L4896] To be more specific, tagraxofusp gets internalized to the IL-3 receptor-expressing cell allowing for diphtheria toxin translocation to the cytosol and followed by the binding to ADP-ribosylation elongation factor 2 which is a key factor for protein translation. Once the protein synthesis is inhibited, the cell goes under a process of apoptosis.[L4895, L4897] As the apoptosis induction requires an active state of protein synthesis, tagraxofusp is not able to perform its apoptotic function in dormant cells.[L4897] | There haven't been analysis observing the carcinogenic, mutagenic potential nor the effect on fertility. However, in studies performed in cynomolgus monkeys at an overdose rate of 1.6 times the recommended dose, it was observed severe kidney tubular degeneration. Similar studies at the recommended dose reported the presence of degeneration and necrosis of choroid plexus in the brain were. This effect seems to be progressive even 3 weeks after therapy withdrawal.[FDA label] | For the metabolism, as tagraxofusp is a fusion protein, it is expected to get processed until small peptides and amino acids by the actions of proteases. | The reported Cmax in clinical trials was of around 23 ng/ml.[L4897] After a 15 min infusion of a dose of 12 mcg/kg the registered AUC and Cmax was 231 mcg.h/L and 162 mcg/L respectively.[FDA label] | In BPDCN patients, the reported volume of distribution is of 5.1 L.[FDA label] | The clearance of tagraxofusp was reported to fit a mono-exponential model.[L4897] The reported clearance rate is reported to be of 7.1 L/h.[FDA label] | Antineoplastic and Immunomodulating Agents | NA | NA | NA | NA | Interleukin-3 receptor subunit alpha,ADP-ribosylation factor-like protein 2 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 15602 | Th1611 | Tagraxofusp | >Th1611_Tagraxofusp MGADDVVDSSKSFVMENFSSYHGTKPGYVDSIQKGIQKPKSGTQGNYDDDWKGFYSTDNKYDAAGYSVDNENPLSGKAGGVVKVTYPGLTKVLALKVDNAETIKKELGLSLTEPLMEQVGTEEFIKRFGDGASRVVLSLPFAEGSSSVEYINNWEQAKALSVELEINFETRGKRGQDAMYEYMAQACAGNRVRRSVGSSLSCINLDWDVIRDKTKTKIESLKEHGPIKNKMSESPNKTVSEEKAKQYLEEFHQTALEHPELSELKTVTGTNPVFAGANYAAWAVNVAQVIDSETADNLEKTTAALSILPGIGSVMGIADGAVHHNTEEIVAQSIALSSLMVAQAIPLVGELVDIGFAAYNFVESIINLFQVVHNSYNRPAYSPGHKTRPHMAPMTQTTSLKTSWVNCSNMIDEIITHLKQPPLPLLDFNNLNGEDQDILMENNLRRPNLEAFNRAVKSLQNASAIESILKNLLPCLPLATAAPTRHPIHIKDGDWNEFRRKLTFYLKTLENAQAQQTTLSLAIF | NA | C2553 H4026 N692 O798 S16 | NA | NA | NA | The reported half-life of tagraxofusp is of around 51 minutes.[L4897] | Tagraxofusp is an IL-3 conjugated truncated diphtheria toxin.[L4895] It is composed by the catalytic and translocation domains of diphtheria toxin fused via Met-His linker to a full-length human IL-3.[L4897, L4898] Tagraxofusp was developed by Stemline Therapeutics Inc and FDA approved on December 21, 2018, as the first therapy for blastic plasmacytoid dendritic cell neoplasm.[L4894] This drug achieved approval after being designated with the title of breakthrough therapy, priority review, and orphan drug status.[L4893] Tagraxofusp has been designated as an orphan drug in the EU since November 2015.[L4898] | Tagraxofusp is indicated for the treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN) in adults and pediatric patients over 2 years old. This treatment allows an alternative for the previous intense treatment which consisted of intensive chemotherapy followed by bone marrow transplantation.[L4893] BPDCN is a rare hematologic malignancy derived from plasmacytoid dendritic cells. It is characterized by the significantly increased expression of cells expressing CD4/CD56/CD123 and other markers restricted to plasmacytoid dendritic cells and a lack of expression of lymphoid, natural killer or myeloid lineage-associated antigens.[A40274] A key feature of the malignant cells is the overexpression of CD123, also known as interleukin-3 receptor, and the constant requirement of IL-3 for survival.[L4897] | In vitro studies showed that BPDCN blasts are ultrasensitive to tagraxofusp by presenting IC50 values in the femtomolar scale.[L4897] One of the main physiological changes of BPDCN is the presence of elevated interferon alpha and to produce an inflammatory response. In trials with tagraxofusp and following cell depletion, there was observed a significant reduction in the levels of interferon alpha and interleukin 6.[L4896] In clinical trials, tagraxofusp reported complete remission and complete remission with a skin abnormality not indicative of active disease in 54% of the treated patients.[L4893] | Tagraxofusp binds to cells expressing the IL-3 receptor and delivers in them the diphtheria toxin after binding. This is very useful as the malignant cells in BPDCN present a particularly high expression of IL-3 receptor (CD123+ pDC).[L4896] To be more specific, tagraxofusp gets internalized to the IL-3 receptor-expressing cell allowing for diphtheria toxin translocation to the cytosol and followed by the binding to ADP-ribosylation elongation factor 2 which is a key factor for protein translation. Once the protein synthesis is inhibited, the cell goes under a process of apoptosis.[L4895, L4897] As the apoptosis induction requires an active state of protein synthesis, tagraxofusp is not able to perform its apoptotic function in dormant cells.[L4897] | There haven't been analysis observing the carcinogenic, mutagenic potential nor the effect on fertility. However, in studies performed in cynomolgus monkeys at an overdose rate of 1.6 times the recommended dose, it was observed severe kidney tubular degeneration. Similar studies at the recommended dose reported the presence of degeneration and necrosis of choroid plexus in the brain were. This effect seems to be progressive even 3 weeks after therapy withdrawal.[FDA label] | For the metabolism, as tagraxofusp is a fusion protein, it is expected to get processed until small peptides and amino acids by the actions of proteases. | The reported Cmax in clinical trials was of around 23 ng/ml.[L4897] After a 15 min infusion of a dose of 12 mcg/kg the registered AUC and Cmax was 231 mcg.h/L and 162 mcg/L respectively.[FDA label] | In BPDCN patients, the reported volume of distribution is of 5.1 L.[FDA label] | The clearance of tagraxofusp was reported to fit a mono-exponential model.[L4897] The reported clearance rate is reported to be of 7.1 L/h.[FDA label] | CD123 Interaction | NA | NA | NA | NA | Interleukin-3 receptor subunit alpha,ADP-ribosylation factor-like protein 2 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 15603 | Th1611 | Tagraxofusp | >Th1611_Tagraxofusp MGADDVVDSSKSFVMENFSSYHGTKPGYVDSIQKGIQKPKSGTQGNYDDDWKGFYSTDNKYDAAGYSVDNENPLSGKAGGVVKVTYPGLTKVLALKVDNAETIKKELGLSLTEPLMEQVGTEEFIKRFGDGASRVVLSLPFAEGSSSVEYINNWEQAKALSVELEINFETRGKRGQDAMYEYMAQACAGNRVRRSVGSSLSCINLDWDVIRDKTKTKIESLKEHGPIKNKMSESPNKTVSEEKAKQYLEEFHQTALEHPELSELKTVTGTNPVFAGANYAAWAVNVAQVIDSETADNLEKTTAALSILPGIGSVMGIADGAVHHNTEEIVAQSIALSSLMVAQAIPLVGELVDIGFAAYNFVESIINLFQVVHNSYNRPAYSPGHKTRPHMAPMTQTTSLKTSWVNCSNMIDEIITHLKQPPLPLLDFNNLNGEDQDILMENNLRRPNLEAFNRAVKSLQNASAIESILKNLLPCLPLATAAPTRHPIHIKDGDWNEFRRKLTFYLKTLENAQAQQTTLSLAIF | NA | C2553 H4026 N692 O798 S16 | NA | NA | NA | The reported half-life of tagraxofusp is of around 51 minutes.[L4897] | Tagraxofusp is an IL-3 conjugated truncated diphtheria toxin.[L4895] It is composed by the catalytic and translocation domains of diphtheria toxin fused via Met-His linker to a full-length human IL-3.[L4897, L4898] Tagraxofusp was developed by Stemline Therapeutics Inc and FDA approved on December 21, 2018, as the first therapy for blastic plasmacytoid dendritic cell neoplasm.[L4894] This drug achieved approval after being designated with the title of breakthrough therapy, priority review, and orphan drug status.[L4893] Tagraxofusp has been designated as an orphan drug in the EU since November 2015.[L4898] | Tagraxofusp is indicated for the treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN) in adults and pediatric patients over 2 years old. This treatment allows an alternative for the previous intense treatment which consisted of intensive chemotherapy followed by bone marrow transplantation.[L4893] BPDCN is a rare hematologic malignancy derived from plasmacytoid dendritic cells. It is characterized by the significantly increased expression of cells expressing CD4/CD56/CD123 and other markers restricted to plasmacytoid dendritic cells and a lack of expression of lymphoid, natural killer or myeloid lineage-associated antigens.[A40274] A key feature of the malignant cells is the overexpression of CD123, also known as interleukin-3 receptor, and the constant requirement of IL-3 for survival.[L4897] | In vitro studies showed that BPDCN blasts are ultrasensitive to tagraxofusp by presenting IC50 values in the femtomolar scale.[L4897] One of the main physiological changes of BPDCN is the presence of elevated interferon alpha and to produce an inflammatory response. In trials with tagraxofusp and following cell depletion, there was observed a significant reduction in the levels of interferon alpha and interleukin 6.[L4896] In clinical trials, tagraxofusp reported complete remission and complete remission with a skin abnormality not indicative of active disease in 54% of the treated patients.[L4893] | Tagraxofusp binds to cells expressing the IL-3 receptor and delivers in them the diphtheria toxin after binding. This is very useful as the malignant cells in BPDCN present a particularly high expression of IL-3 receptor (CD123+ pDC).[L4896] To be more specific, tagraxofusp gets internalized to the IL-3 receptor-expressing cell allowing for diphtheria toxin translocation to the cytosol and followed by the binding to ADP-ribosylation elongation factor 2 which is a key factor for protein translation. Once the protein synthesis is inhibited, the cell goes under a process of apoptosis.[L4895, L4897] As the apoptosis induction requires an active state of protein synthesis, tagraxofusp is not able to perform its apoptotic function in dormant cells.[L4897] | There haven't been analysis observing the carcinogenic, mutagenic potential nor the effect on fertility. However, in studies performed in cynomolgus monkeys at an overdose rate of 1.6 times the recommended dose, it was observed severe kidney tubular degeneration. Similar studies at the recommended dose reported the presence of degeneration and necrosis of choroid plexus in the brain were. This effect seems to be progressive even 3 weeks after therapy withdrawal.[FDA label] | For the metabolism, as tagraxofusp is a fusion protein, it is expected to get processed until small peptides and amino acids by the actions of proteases. | The reported Cmax in clinical trials was of around 23 ng/ml.[L4897] After a 15 min infusion of a dose of 12 mcg/kg the registered AUC and Cmax was 231 mcg.h/L and 162 mcg/L respectively.[FDA label] | In BPDCN patients, the reported volume of distribution is of 5.1 L.[FDA label] | The clearance of tagraxofusp was reported to fit a mono-exponential model.[L4897] The reported clearance rate is reported to be of 7.1 L/h.[FDA label] | CD123 Interactions | NA | NA | NA | NA | Interleukin-3 receptor subunit alpha,ADP-ribosylation factor-like protein 2 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 15604 | Th1611 | Tagraxofusp | >Th1611_Tagraxofusp MGADDVVDSSKSFVMENFSSYHGTKPGYVDSIQKGIQKPKSGTQGNYDDDWKGFYSTDNKYDAAGYSVDNENPLSGKAGGVVKVTYPGLTKVLALKVDNAETIKKELGLSLTEPLMEQVGTEEFIKRFGDGASRVVLSLPFAEGSSSVEYINNWEQAKALSVELEINFETRGKRGQDAMYEYMAQACAGNRVRRSVGSSLSCINLDWDVIRDKTKTKIESLKEHGPIKNKMSESPNKTVSEEKAKQYLEEFHQTALEHPELSELKTVTGTNPVFAGANYAAWAVNVAQVIDSETADNLEKTTAALSILPGIGSVMGIADGAVHHNTEEIVAQSIALSSLMVAQAIPLVGELVDIGFAAYNFVESIINLFQVVHNSYNRPAYSPGHKTRPHMAPMTQTTSLKTSWVNCSNMIDEIITHLKQPPLPLLDFNNLNGEDQDILMENNLRRPNLEAFNRAVKSLQNASAIESILKNLLPCLPLATAAPTRHPIHIKDGDWNEFRRKLTFYLKTLENAQAQQTTLSLAIF | NA | C2553 H4026 N692 O798 S16 | NA | NA | NA | The reported half-life of tagraxofusp is of around 51 minutes.[L4897] | Tagraxofusp is an IL-3 conjugated truncated diphtheria toxin.[L4895] It is composed by the catalytic and translocation domains of diphtheria toxin fused via Met-His linker to a full-length human IL-3.[L4897, L4898] Tagraxofusp was developed by Stemline Therapeutics Inc and FDA approved on December 21, 2018, as the first therapy for blastic plasmacytoid dendritic cell neoplasm.[L4894] This drug achieved approval after being designated with the title of breakthrough therapy, priority review, and orphan drug status.[L4893] Tagraxofusp has been designated as an orphan drug in the EU since November 2015.[L4898] | Tagraxofusp is indicated for the treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN) in adults and pediatric patients over 2 years old. This treatment allows an alternative for the previous intense treatment which consisted of intensive chemotherapy followed by bone marrow transplantation.[L4893] BPDCN is a rare hematologic malignancy derived from plasmacytoid dendritic cells. It is characterized by the significantly increased expression of cells expressing CD4/CD56/CD123 and other markers restricted to plasmacytoid dendritic cells and a lack of expression of lymphoid, natural killer or myeloid lineage-associated antigens.[A40274] A key feature of the malignant cells is the overexpression of CD123, also known as interleukin-3 receptor, and the constant requirement of IL-3 for survival.[L4897] | In vitro studies showed that BPDCN blasts are ultrasensitive to tagraxofusp by presenting IC50 values in the femtomolar scale.[L4897] One of the main physiological changes of BPDCN is the presence of elevated interferon alpha and to produce an inflammatory response. In trials with tagraxofusp and following cell depletion, there was observed a significant reduction in the levels of interferon alpha and interleukin 6.[L4896] In clinical trials, tagraxofusp reported complete remission and complete remission with a skin abnormality not indicative of active disease in 54% of the treated patients.[L4893] | Tagraxofusp binds to cells expressing the IL-3 receptor and delivers in them the diphtheria toxin after binding. This is very useful as the malignant cells in BPDCN present a particularly high expression of IL-3 receptor (CD123+ pDC).[L4896] To be more specific, tagraxofusp gets internalized to the IL-3 receptor-expressing cell allowing for diphtheria toxin translocation to the cytosol and followed by the binding to ADP-ribosylation elongation factor 2 which is a key factor for protein translation. Once the protein synthesis is inhibited, the cell goes under a process of apoptosis.[L4895, L4897] As the apoptosis induction requires an active state of protein synthesis, tagraxofusp is not able to perform its apoptotic function in dormant cells.[L4897] | There haven't been analysis observing the carcinogenic, mutagenic potential nor the effect on fertility. However, in studies performed in cynomolgus monkeys at an overdose rate of 1.6 times the recommended dose, it was observed severe kidney tubular degeneration. Similar studies at the recommended dose reported the presence of degeneration and necrosis of choroid plexus in the brain were. This effect seems to be progressive even 3 weeks after therapy withdrawal.[FDA label] | For the metabolism, as tagraxofusp is a fusion protein, it is expected to get processed until small peptides and amino acids by the actions of proteases. | The reported Cmax in clinical trials was of around 23 ng/ml.[L4897] After a 15 min infusion of a dose of 12 mcg/kg the registered AUC and Cmax was 231 mcg.h/L and 162 mcg/L respectively.[FDA label] | In BPDCN patients, the reported volume of distribution is of 5.1 L.[FDA label] | The clearance of tagraxofusp was reported to fit a mono-exponential model.[L4897] The reported clearance rate is reported to be of 7.1 L/h.[FDA label] | Cytotoxins | NA | NA | NA | NA | Interleukin-3 receptor subunit alpha,ADP-ribosylation factor-like protein 2 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 15605 | Th1611 | Tagraxofusp | >Th1611_Tagraxofusp MGADDVVDSSKSFVMENFSSYHGTKPGYVDSIQKGIQKPKSGTQGNYDDDWKGFYSTDNKYDAAGYSVDNENPLSGKAGGVVKVTYPGLTKVLALKVDNAETIKKELGLSLTEPLMEQVGTEEFIKRFGDGASRVVLSLPFAEGSSSVEYINNWEQAKALSVELEINFETRGKRGQDAMYEYMAQACAGNRVRRSVGSSLSCINLDWDVIRDKTKTKIESLKEHGPIKNKMSESPNKTVSEEKAKQYLEEFHQTALEHPELSELKTVTGTNPVFAGANYAAWAVNVAQVIDSETADNLEKTTAALSILPGIGSVMGIADGAVHHNTEEIVAQSIALSSLMVAQAIPLVGELVDIGFAAYNFVESIINLFQVVHNSYNRPAYSPGHKTRPHMAPMTQTTSLKTSWVNCSNMIDEIITHLKQPPLPLLDFNNLNGEDQDILMENNLRRPNLEAFNRAVKSLQNASAIESILKNLLPCLPLATAAPTRHPIHIKDGDWNEFRRKLTFYLKTLENAQAQQTTLSLAIF | NA | C2553 H4026 N692 O798 S16 | NA | NA | NA | The reported half-life of tagraxofusp is of around 51 minutes.[L4897] | Tagraxofusp is an IL-3 conjugated truncated diphtheria toxin.[L4895] It is composed by the catalytic and translocation domains of diphtheria toxin fused via Met-His linker to a full-length human IL-3.[L4897, L4898] Tagraxofusp was developed by Stemline Therapeutics Inc and FDA approved on December 21, 2018, as the first therapy for blastic plasmacytoid dendritic cell neoplasm.[L4894] This drug achieved approval after being designated with the title of breakthrough therapy, priority review, and orphan drug status.[L4893] Tagraxofusp has been designated as an orphan drug in the EU since November 2015.[L4898] | Tagraxofusp is indicated for the treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN) in adults and pediatric patients over 2 years old. This treatment allows an alternative for the previous intense treatment which consisted of intensive chemotherapy followed by bone marrow transplantation.[L4893] BPDCN is a rare hematologic malignancy derived from plasmacytoid dendritic cells. It is characterized by the significantly increased expression of cells expressing CD4/CD56/CD123 and other markers restricted to plasmacytoid dendritic cells and a lack of expression of lymphoid, natural killer or myeloid lineage-associated antigens.[A40274] A key feature of the malignant cells is the overexpression of CD123, also known as interleukin-3 receptor, and the constant requirement of IL-3 for survival.[L4897] | In vitro studies showed that BPDCN blasts are ultrasensitive to tagraxofusp by presenting IC50 values in the femtomolar scale.[L4897] One of the main physiological changes of BPDCN is the presence of elevated interferon alpha and to produce an inflammatory response. In trials with tagraxofusp and following cell depletion, there was observed a significant reduction in the levels of interferon alpha and interleukin 6.[L4896] In clinical trials, tagraxofusp reported complete remission and complete remission with a skin abnormality not indicative of active disease in 54% of the treated patients.[L4893] | Tagraxofusp binds to cells expressing the IL-3 receptor and delivers in them the diphtheria toxin after binding. This is very useful as the malignant cells in BPDCN present a particularly high expression of IL-3 receptor (CD123+ pDC).[L4896] To be more specific, tagraxofusp gets internalized to the IL-3 receptor-expressing cell allowing for diphtheria toxin translocation to the cytosol and followed by the binding to ADP-ribosylation elongation factor 2 which is a key factor for protein translation. Once the protein synthesis is inhibited, the cell goes under a process of apoptosis.[L4895, L4897] As the apoptosis induction requires an active state of protein synthesis, tagraxofusp is not able to perform its apoptotic function in dormant cells.[L4897] | There haven't been analysis observing the carcinogenic, mutagenic potential nor the effect on fertility. However, in studies performed in cynomolgus monkeys at an overdose rate of 1.6 times the recommended dose, it was observed severe kidney tubular degeneration. Similar studies at the recommended dose reported the presence of degeneration and necrosis of choroid plexus in the brain were. This effect seems to be progressive even 3 weeks after therapy withdrawal.[FDA label] | For the metabolism, as tagraxofusp is a fusion protein, it is expected to get processed until small peptides and amino acids by the actions of proteases. | The reported Cmax in clinical trials was of around 23 ng/ml.[L4897] After a 15 min infusion of a dose of 12 mcg/kg the registered AUC and Cmax was 231 mcg.h/L and 162 mcg/L respectively.[FDA label] | In BPDCN patients, the reported volume of distribution is of 5.1 L.[FDA label] | The clearance of tagraxofusp was reported to fit a mono-exponential model.[L4897] The reported clearance rate is reported to be of 7.1 L/h.[FDA label] | Narrow Therapeutic Index Drugs | NA | NA | NA | NA | Interleukin-3 receptor subunit alpha,ADP-ribosylation factor-like protein 2 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 15606 | Th1611 | Tagraxofusp | >Th1611_Tagraxofusp MGADDVVDSSKSFVMENFSSYHGTKPGYVDSIQKGIQKPKSGTQGNYDDDWKGFYSTDNKYDAAGYSVDNENPLSGKAGGVVKVTYPGLTKVLALKVDNAETIKKELGLSLTEPLMEQVGTEEFIKRFGDGASRVVLSLPFAEGSSSVEYINNWEQAKALSVELEINFETRGKRGQDAMYEYMAQACAGNRVRRSVGSSLSCINLDWDVIRDKTKTKIESLKEHGPIKNKMSESPNKTVSEEKAKQYLEEFHQTALEHPELSELKTVTGTNPVFAGANYAAWAVNVAQVIDSETADNLEKTTAALSILPGIGSVMGIADGAVHHNTEEIVAQSIALSSLMVAQAIPLVGELVDIGFAAYNFVESIINLFQVVHNSYNRPAYSPGHKTRPHMAPMTQTTSLKTSWVNCSNMIDEIITHLKQPPLPLLDFNNLNGEDQDILMENNLRRPNLEAFNRAVKSLQNASAIESILKNLLPCLPLATAAPTRHPIHIKDGDWNEFRRKLTFYLKTLENAQAQQTTLSLAIF | NA | C2553 H4026 N692 O798 S16 | NA | NA | NA | The reported half-life of tagraxofusp is of around 51 minutes.[L4897] | Tagraxofusp is an IL-3 conjugated truncated diphtheria toxin.[L4895] It is composed by the catalytic and translocation domains of diphtheria toxin fused via Met-His linker to a full-length human IL-3.[L4897, L4898] Tagraxofusp was developed by Stemline Therapeutics Inc and FDA approved on December 21, 2018, as the first therapy for blastic plasmacytoid dendritic cell neoplasm.[L4894] This drug achieved approval after being designated with the title of breakthrough therapy, priority review, and orphan drug status.[L4893] Tagraxofusp has been designated as an orphan drug in the EU since November 2015.[L4898] | Tagraxofusp is indicated for the treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN) in adults and pediatric patients over 2 years old. This treatment allows an alternative for the previous intense treatment which consisted of intensive chemotherapy followed by bone marrow transplantation.[L4893] BPDCN is a rare hematologic malignancy derived from plasmacytoid dendritic cells. It is characterized by the significantly increased expression of cells expressing CD4/CD56/CD123 and other markers restricted to plasmacytoid dendritic cells and a lack of expression of lymphoid, natural killer or myeloid lineage-associated antigens.[A40274] A key feature of the malignant cells is the overexpression of CD123, also known as interleukin-3 receptor, and the constant requirement of IL-3 for survival.[L4897] | In vitro studies showed that BPDCN blasts are ultrasensitive to tagraxofusp by presenting IC50 values in the femtomolar scale.[L4897] One of the main physiological changes of BPDCN is the presence of elevated interferon alpha and to produce an inflammatory response. In trials with tagraxofusp and following cell depletion, there was observed a significant reduction in the levels of interferon alpha and interleukin 6.[L4896] In clinical trials, tagraxofusp reported complete remission and complete remission with a skin abnormality not indicative of active disease in 54% of the treated patients.[L4893] | Tagraxofusp binds to cells expressing the IL-3 receptor and delivers in them the diphtheria toxin after binding. This is very useful as the malignant cells in BPDCN present a particularly high expression of IL-3 receptor (CD123+ pDC).[L4896] To be more specific, tagraxofusp gets internalized to the IL-3 receptor-expressing cell allowing for diphtheria toxin translocation to the cytosol and followed by the binding to ADP-ribosylation elongation factor 2 which is a key factor for protein translation. Once the protein synthesis is inhibited, the cell goes under a process of apoptosis.[L4895, L4897] As the apoptosis induction requires an active state of protein synthesis, tagraxofusp is not able to perform its apoptotic function in dormant cells.[L4897] | There haven't been analysis observing the carcinogenic, mutagenic potential nor the effect on fertility. However, in studies performed in cynomolgus monkeys at an overdose rate of 1.6 times the recommended dose, it was observed severe kidney tubular degeneration. Similar studies at the recommended dose reported the presence of degeneration and necrosis of choroid plexus in the brain were. This effect seems to be progressive even 3 weeks after therapy withdrawal.[FDA label] | For the metabolism, as tagraxofusp is a fusion protein, it is expected to get processed until small peptides and amino acids by the actions of proteases. | The reported Cmax in clinical trials was of around 23 ng/ml.[L4897] After a 15 min infusion of a dose of 12 mcg/kg the registered AUC and Cmax was 231 mcg.h/L and 162 mcg/L respectively.[FDA label] | In BPDCN patients, the reported volume of distribution is of 5.1 L.[FDA label] | The clearance of tagraxofusp was reported to fit a mono-exponential model.[L4897] The reported clearance rate is reported to be of 7.1 L/h.[FDA label] | Proteins | NA | NA | NA | NA | Interleukin-3 receptor subunit alpha,ADP-ribosylation factor-like protein 2 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 15607 | Th1611 | Tagraxofusp | >Th1611_Tagraxofusp MGADDVVDSSKSFVMENFSSYHGTKPGYVDSIQKGIQKPKSGTQGNYDDDWKGFYSTDNKYDAAGYSVDNENPLSGKAGGVVKVTYPGLTKVLALKVDNAETIKKELGLSLTEPLMEQVGTEEFIKRFGDGASRVVLSLPFAEGSSSVEYINNWEQAKALSVELEINFETRGKRGQDAMYEYMAQACAGNRVRRSVGSSLSCINLDWDVIRDKTKTKIESLKEHGPIKNKMSESPNKTVSEEKAKQYLEEFHQTALEHPELSELKTVTGTNPVFAGANYAAWAVNVAQVIDSETADNLEKTTAALSILPGIGSVMGIADGAVHHNTEEIVAQSIALSSLMVAQAIPLVGELVDIGFAAYNFVESIINLFQVVHNSYNRPAYSPGHKTRPHMAPMTQTTSLKTSWVNCSNMIDEIITHLKQPPLPLLDFNNLNGEDQDILMENNLRRPNLEAFNRAVKSLQNASAIESILKNLLPCLPLATAAPTRHPIHIKDGDWNEFRRKLTFYLKTLENAQAQQTTLSLAIF | NA | C2553 H4026 N692 O798 S16 | NA | NA | NA | The reported half-life of tagraxofusp is of around 51 minutes.[L4897] | Tagraxofusp is an IL-3 conjugated truncated diphtheria toxin.[L4895] It is composed by the catalytic and translocation domains of diphtheria toxin fused via Met-His linker to a full-length human IL-3.[L4897, L4898] Tagraxofusp was developed by Stemline Therapeutics Inc and FDA approved on December 21, 2018, as the first therapy for blastic plasmacytoid dendritic cell neoplasm.[L4894] This drug achieved approval after being designated with the title of breakthrough therapy, priority review, and orphan drug status.[L4893] Tagraxofusp has been designated as an orphan drug in the EU since November 2015.[L4898] | Tagraxofusp is indicated for the treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN) in adults and pediatric patients over 2 years old. This treatment allows an alternative for the previous intense treatment which consisted of intensive chemotherapy followed by bone marrow transplantation.[L4893] BPDCN is a rare hematologic malignancy derived from plasmacytoid dendritic cells. It is characterized by the significantly increased expression of cells expressing CD4/CD56/CD123 and other markers restricted to plasmacytoid dendritic cells and a lack of expression of lymphoid, natural killer or myeloid lineage-associated antigens.[A40274] A key feature of the malignant cells is the overexpression of CD123, also known as interleukin-3 receptor, and the constant requirement of IL-3 for survival.[L4897] | In vitro studies showed that BPDCN blasts are ultrasensitive to tagraxofusp by presenting IC50 values in the femtomolar scale.[L4897] One of the main physiological changes of BPDCN is the presence of elevated interferon alpha and to produce an inflammatory response. In trials with tagraxofusp and following cell depletion, there was observed a significant reduction in the levels of interferon alpha and interleukin 6.[L4896] In clinical trials, tagraxofusp reported complete remission and complete remission with a skin abnormality not indicative of active disease in 54% of the treated patients.[L4893] | Tagraxofusp binds to cells expressing the IL-3 receptor and delivers in them the diphtheria toxin after binding. This is very useful as the malignant cells in BPDCN present a particularly high expression of IL-3 receptor (CD123+ pDC).[L4896] To be more specific, tagraxofusp gets internalized to the IL-3 receptor-expressing cell allowing for diphtheria toxin translocation to the cytosol and followed by the binding to ADP-ribosylation elongation factor 2 which is a key factor for protein translation. Once the protein synthesis is inhibited, the cell goes under a process of apoptosis.[L4895, L4897] As the apoptosis induction requires an active state of protein synthesis, tagraxofusp is not able to perform its apoptotic function in dormant cells.[L4897] | There haven't been analysis observing the carcinogenic, mutagenic potential nor the effect on fertility. However, in studies performed in cynomolgus monkeys at an overdose rate of 1.6 times the recommended dose, it was observed severe kidney tubular degeneration. Similar studies at the recommended dose reported the presence of degeneration and necrosis of choroid plexus in the brain were. This effect seems to be progressive even 3 weeks after therapy withdrawal.[FDA label] | For the metabolism, as tagraxofusp is a fusion protein, it is expected to get processed until small peptides and amino acids by the actions of proteases. | The reported Cmax in clinical trials was of around 23 ng/ml.[L4897] After a 15 min infusion of a dose of 12 mcg/kg the registered AUC and Cmax was 231 mcg.h/L and 162 mcg/L respectively.[FDA label] | In BPDCN patients, the reported volume of distribution is of 5.1 L.[FDA label] | The clearance of tagraxofusp was reported to fit a mono-exponential model.[L4897] The reported clearance rate is reported to be of 7.1 L/h.[FDA label] | Recombinant Fusion Proteins | NA | NA | NA | NA | Interleukin-3 receptor subunit alpha,ADP-ribosylation factor-like protein 2 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |
| 15608 | Th1611 | Tagraxofusp | >Th1611_Tagraxofusp MGADDVVDSSKSFVMENFSSYHGTKPGYVDSIQKGIQKPKSGTQGNYDDDWKGFYSTDNKYDAAGYSVDNENPLSGKAGGVVKVTYPGLTKVLALKVDNAETIKKELGLSLTEPLMEQVGTEEFIKRFGDGASRVVLSLPFAEGSSSVEYINNWEQAKALSVELEINFETRGKRGQDAMYEYMAQACAGNRVRRSVGSSLSCINLDWDVIRDKTKTKIESLKEHGPIKNKMSESPNKTVSEEKAKQYLEEFHQTALEHPELSELKTVTGTNPVFAGANYAAWAVNVAQVIDSETADNLEKTTAALSILPGIGSVMGIADGAVHHNTEEIVAQSIALSSLMVAQAIPLVGELVDIGFAAYNFVESIINLFQVVHNSYNRPAYSPGHKTRPHMAPMTQTTSLKTSWVNCSNMIDEIITHLKQPPLPLLDFNNLNGEDQDILMENNLRRPNLEAFNRAVKSLQNASAIESILKNLLPCLPLATAAPTRHPIHIKDGDWNEFRRKLTFYLKTLENAQAQQTTLSLAIF | NA | C2553 H4026 N692 O798 S16 | NA | NA | NA | The reported half-life of tagraxofusp is of around 51 minutes.[L4897] | Tagraxofusp is an IL-3 conjugated truncated diphtheria toxin.[L4895] It is composed by the catalytic and translocation domains of diphtheria toxin fused via Met-His linker to a full-length human IL-3.[L4897, L4898] Tagraxofusp was developed by Stemline Therapeutics Inc and FDA approved on December 21, 2018, as the first therapy for blastic plasmacytoid dendritic cell neoplasm.[L4894] This drug achieved approval after being designated with the title of breakthrough therapy, priority review, and orphan drug status.[L4893] Tagraxofusp has been designated as an orphan drug in the EU since November 2015.[L4898] | Tagraxofusp is indicated for the treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN) in adults and pediatric patients over 2 years old. This treatment allows an alternative for the previous intense treatment which consisted of intensive chemotherapy followed by bone marrow transplantation.[L4893] BPDCN is a rare hematologic malignancy derived from plasmacytoid dendritic cells. It is characterized by the significantly increased expression of cells expressing CD4/CD56/CD123 and other markers restricted to plasmacytoid dendritic cells and a lack of expression of lymphoid, natural killer or myeloid lineage-associated antigens.[A40274] A key feature of the malignant cells is the overexpression of CD123, also known as interleukin-3 receptor, and the constant requirement of IL-3 for survival.[L4897] | In vitro studies showed that BPDCN blasts are ultrasensitive to tagraxofusp by presenting IC50 values in the femtomolar scale.[L4897] One of the main physiological changes of BPDCN is the presence of elevated interferon alpha and to produce an inflammatory response. In trials with tagraxofusp and following cell depletion, there was observed a significant reduction in the levels of interferon alpha and interleukin 6.[L4896] In clinical trials, tagraxofusp reported complete remission and complete remission with a skin abnormality not indicative of active disease in 54% of the treated patients.[L4893] | Tagraxofusp binds to cells expressing the IL-3 receptor and delivers in them the diphtheria toxin after binding. This is very useful as the malignant cells in BPDCN present a particularly high expression of IL-3 receptor (CD123+ pDC).[L4896] To be more specific, tagraxofusp gets internalized to the IL-3 receptor-expressing cell allowing for diphtheria toxin translocation to the cytosol and followed by the binding to ADP-ribosylation elongation factor 2 which is a key factor for protein translation. Once the protein synthesis is inhibited, the cell goes under a process of apoptosis.[L4895, L4897] As the apoptosis induction requires an active state of protein synthesis, tagraxofusp is not able to perform its apoptotic function in dormant cells.[L4897] | There haven't been analysis observing the carcinogenic, mutagenic potential nor the effect on fertility. However, in studies performed in cynomolgus monkeys at an overdose rate of 1.6 times the recommended dose, it was observed severe kidney tubular degeneration. Similar studies at the recommended dose reported the presence of degeneration and necrosis of choroid plexus in the brain were. This effect seems to be progressive even 3 weeks after therapy withdrawal.[FDA label] | For the metabolism, as tagraxofusp is a fusion protein, it is expected to get processed until small peptides and amino acids by the actions of proteases. | The reported Cmax in clinical trials was of around 23 ng/ml.[L4897] After a 15 min infusion of a dose of 12 mcg/kg the registered AUC and Cmax was 231 mcg.h/L and 162 mcg/L respectively.[FDA label] | In BPDCN patients, the reported volume of distribution is of 5.1 L.[FDA label] | The clearance of tagraxofusp was reported to fit a mono-exponential model.[L4897] The reported clearance rate is reported to be of 7.1 L/h.[FDA label] | Recombinant Proteins | NA | NA | NA | NA | Interleukin-3 receptor subunit alpha,ADP-ribosylation factor-like protein 2 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | Link | NA | NA |