Detailed description page of ThPDB2
| This page displays user query in tabular form. |
Th1624 details |
| Primary information | |
|---|---|
| ID | 15754 |
| Therapeutic ID | Th1624 |
| Protein Name | Ropeginterferon alfa-2b |
| Sequence | >Th1624_Ropeginterferon_alfa-2b PCDLPQTHSLGSRRTLMLLAQMRRISLFSCLKDRHDFGFPQEEFGNQFQKAETIPVLHEMIQQIFNLFSTKDSSAAWDETLLDKFYTELYQQLNDLEACVIQGVGVTETPLMKEDSILAVRKYFQRITLYLKEKKYSPCAWEVVRAEIMRSFSLSTNLQESLRSKE |
| Molecular Weight | 60000 |
| Chemical Formula | C16H29N3O6(C2H4O)n(C2H4O)n |
| Isoelectric Point | NA |
| Hydrophobicity | NA |
| Melting point | NA |
| Half-life | Ropeginterferon alfa-2b administered to polycythemia vera patients over a dose range of 100-500 µg has a half-life of approximately seven days.[L39170] |
| Description | Polycythemia vera (PV) is the most common Philadelphia chromosome-negative myeloproliferative neoplasm (MPN), characterized by increased hematocrit and platelet/leukocyte counts, an increased risk for hemorrhage and thromboembolic events, and a long-term propensity for myelofibrosis and leukemia.[A242000, A242005] [Interferon alfa-2b] has been used for decades to treat PV but requires frequent dosing and is not tolerated by all patients.[A242005] Ropeginterferon alfa-2b is a next-generation mono-pegylated type I interferon produced from proline-IFN-a-2b in _Escherichia coli_ that has high tolerability and a long half-life.[A242015, L39170] Ropeginterferon alfa-2b has shown efficacy in PV in _in vitro_ and _in vivo_ models and clinical trials.[A242010, A242015] Ropeginterferon alfa-2b was approved by the FDA on November 12, 2021, and is currently marketed under the trademark BESREMi by PharmaEssentia Corporation.[L39170] |
| Indication/Disease | Ropeginterferon alfa-2b is indicated for the treatment of adult patients with polycythemia vera.[L39170] |
| Pharmacodynamics | Ropeginterferon alfa-2b acts through the interferon-alpha/beta receptor to initiate downstream JAK/STAT signalling leading to its therapeutic effects. Like other interferon alfa products, ropeginterferon alfa-2b may cause various toxicities, including endocrine, cardiovascular, pulmonary, ophthalmologic, dental/periodontal, renal, and dermatological toxicity. In addition, interferon alfa has been associated with hepatotoxicity, including increases in serum ALT, AST, GGT, and bilirubin; ropeginterferon alfa-2b is contraindicated in patients with moderate to severe (Child-Pugh B or C) hepatic impairment. Pancreatitis and colitis, including fatal ulcerative/hemorrhagic/ischemic colitis, have occurred in patients treated with interferon alfa. Significant toxicity of any kind may require treatment discontinuation. Interferon alfa treatment has decreased peripheral blood counts, including thrombocytopenia and leukopenia, and altered lipid levels, including hyperlipidemia, hypertriglyceridemia, and dyslipidemia. Hypersensitivity reactions, including anaphylaxis, may occur; ropeginterferon alfa-2b is contraindicated in hypersensitive patients and those with known hypersensitivity to other interferons. Life-threatening or fatal neuropsychiatric reactions may occur, including in patients without prior history; ropeginterferon alfa-2b is contraindicated in patients with a history of severe psychiatric disorders. Finally, ropeginterferon alfa-2b can cause fetal harm and should be used with caution in females of reproductive potential.[L39170] |
| Mechanism of Action | Polycythemia vera (PV) is the most common Philadelphia chromosome-negative myeloproliferative neoplasm (MPN), which also includes essential thrombocytopenia and myelofibrosis.[A242000, A242005] PV is characterized by increased hematocrit and platelet/leukocyte counts, an increased risk for hemorrhage and thromboembolic events, and a long-term propensity for myelofibrosis and leukemia. The main driver mutation, _JAK2_ V617F, is present in >95% of PV patients and results in constitutive JAK/STAT signalling; other exon 12 mutations in _JAK2_ may also result in PV. PV results in clonal hematopoietic stem cells, such that they form endogenous erythroid colonies (EECs) _in vitro_.[A242000] Interferon alfa-2b has been used for decades in PV despite the lack of formal approval.[A242005] Although the mechanism of action is unclear, interferon alfa-2b is known to bind the interferon-alpha/beta receptor (IFNAR) and activate downstream JAK/STAT signalling.[A242005, L39170] The overall result is a series of anti-proliferative, anti-angiogenic, pro-apoptotic, and immunomodulatory effects, including augmenting T-cell, macrophage, and natural killer cells.[A242005] Interestingly, _in vitro_ studies have revealed that ropeginterferon alfa-2b is specific to some extent for _JAK2_-mutant EECs, a result that is in line with the reduced allelic burden observed in clinical trials.[A242010, A242015] Partial and complete molecular and hematological responses have been achieved with ropeginterferon alfa-2b.[A242015] |
| Toxicity | Ropeginterferon alfa-2b overdose may present with influenza-like symptoms or other adverse reactions. As there is no known antidote, symptomatic and supportive care should be administered in the result of an overdose. Ropeginterferon alfa-2b is not mutagenic in standard assays but has not been tested for carcinogenic potential.[L39170] |
| Metabolism | Ropeginterferon alfa-2b is expected to be catabolized by various proteolytic enzymes.[L15811] |
| Absorption | In patients with polycythemia vera on a two-week dosing interval, the estimated steady-state Cmin was 1.4-12 ng/mL, Cmax was 4.4-31 ng/mL, and AUC was 1011-7809 ng |
| Ropeginterferon alfa-2b has an estimated geometric mean apparent volume of distribution (%CV) of 4.8 L (21%) in polycythemia vera patients.[L39170] | |
| Clearance | Ropeginterferon alfa-2b administered to polycythemia vera patients over a dose range of 100-500 µg has a clearance of 1.7-2.5 L/h.[L39170] |
| Categories | Adjuvants, Immunologic |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Interferon alpha/beta receptor (IFNAR) |
| Brand Name | BESREMi |
| Company | PharmaEssentia USA |
| Brand Description | PharmaEssentia USA |
| Prescribed For | Subcutaneous |
| Chemical Name | 500 ug/1mL |
| Formulation | BESREMi is contraindicated in patients with: Existence of, or history of severe psychiatric disorders, particularly severe depression, suicidal ideation, or suicide attempt Hypersensitivity to interferons including interferon alfa-2b or any of the inactive ingredients of BESREMi. Moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment History or presence of active serious or untreated autoimmune disease Immunosuppressed transplant recipients |
| Physical Appearance | influenza-like illness, joint pain, fatigue, itching, runny or stuffy nose, musculoskeletal pain, headache, diarrhea, increased sweating, nausea, upper respiratory tract infection, local administration site reactions, dizziness, abdominal pain, depression, sleep problems (insomnia, abnormal dreams), low white blood cell count (leukopenia, neutropenia), decreased appetite, hair loss, fluid retention (edema), high blood pressure (hypertension), muscle spasms, rash, transaminase elevations, urinary tract infection (UTI), low blood platelets (thrombocytopenia), and spinning sensation (vertigo). |
| Route of Administration | Besremi is a prescription medicine that is used to treat adults with polycythemia vera. It is not known if this medicine is safe and effective in children. Important information Besremi can cause serious side effects that: may cause death, or may worsen certain serious diseases that you may already have... |
| Recommended Dosage | Besremi is a prescription medicine used to treat the symptoms of Polycythemia Vera. Besremi may be used alone or with other medications. |
| Contraindication | (2S)-1-[3,7-bis(2-methoxyethoxycarbonylamino)heptyl]pyrrolidine-2-carboxylic acid |
| Side Effects | Ropeginterferon alfa-2b-njft, an interferon alfa-2b, is an N-terminal monopegylated covalent conjugate of proline interferon alfa-2b, produced in Escherichia coli cells by recombinant DNA technology, with a methoxy polyethylene glycol (mPEG) moiety. Ropeginterferon alfa-2b-njft has an approximate molecular weight of 60 kDa and the approximate molecular weight of the PEG portion of the molecule is 40 kDa. |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 15755 |
| Therapeutic ID | Th1624 |
| Protein Name | Ropeginterferon alfa-2b |
| Sequence | >Th1624_Ropeginterferon_alfa-2b PCDLPQTHSLGSRRTLMLLAQMRRISLFSCLKDRHDFGFPQEEFGNQFQKAETIPVLHEMIQQIFNLFSTKDSSAAWDETLLDKFYTELYQQLNDLEACVIQGVGVTETPLMKEDSILAVRKYFQRITLYLKEKKYSPCAWEVVRAEIMRSFSLSTNLQESLRSKE |
| Molecular Weight | 60000 |
| Chemical Formula | C16H29N3O6(C2H4O)n(C2H4O)n |
| Isoelectric Point | NA |
| Hydrophobicity | NA |
| Melting point | NA |
| Half-life | Ropeginterferon alfa-2b administered to polycythemia vera patients over a dose range of 100-500 µg has a half-life of approximately seven days.[L39170] |
| Description | Polycythemia vera (PV) is the most common Philadelphia chromosome-negative myeloproliferative neoplasm (MPN), characterized by increased hematocrit and platelet/leukocyte counts, an increased risk for hemorrhage and thromboembolic events, and a long-term propensity for myelofibrosis and leukemia.[A242000, A242005] [Interferon alfa-2b] has been used for decades to treat PV but requires frequent dosing and is not tolerated by all patients.[A242005] Ropeginterferon alfa-2b is a next-generation mono-pegylated type I interferon produced from proline-IFN-a-2b in _Escherichia coli_ that has high tolerability and a long half-life.[A242015, L39170] Ropeginterferon alfa-2b has shown efficacy in PV in _in vitro_ and _in vivo_ models and clinical trials.[A242010, A242015] Ropeginterferon alfa-2b was approved by the FDA on November 12, 2021, and is currently marketed under the trademark BESREMi by PharmaEssentia Corporation.[L39170] |
| Indication/Disease | Ropeginterferon alfa-2b is indicated for the treatment of adult patients with polycythemia vera.[L39170] |
| Pharmacodynamics | Ropeginterferon alfa-2b acts through the interferon-alpha/beta receptor to initiate downstream JAK/STAT signalling leading to its therapeutic effects. Like other interferon alfa products, ropeginterferon alfa-2b may cause various toxicities, including endocrine, cardiovascular, pulmonary, ophthalmologic, dental/periodontal, renal, and dermatological toxicity. In addition, interferon alfa has been associated with hepatotoxicity, including increases in serum ALT, AST, GGT, and bilirubin; ropeginterferon alfa-2b is contraindicated in patients with moderate to severe (Child-Pugh B or C) hepatic impairment. Pancreatitis and colitis, including fatal ulcerative/hemorrhagic/ischemic colitis, have occurred in patients treated with interferon alfa. Significant toxicity of any kind may require treatment discontinuation. Interferon alfa treatment has decreased peripheral blood counts, including thrombocytopenia and leukopenia, and altered lipid levels, including hyperlipidemia, hypertriglyceridemia, and dyslipidemia. Hypersensitivity reactions, including anaphylaxis, may occur; ropeginterferon alfa-2b is contraindicated in hypersensitive patients and those with known hypersensitivity to other interferons. Life-threatening or fatal neuropsychiatric reactions may occur, including in patients without prior history; ropeginterferon alfa-2b is contraindicated in patients with a history of severe psychiatric disorders. Finally, ropeginterferon alfa-2b can cause fetal harm and should be used with caution in females of reproductive potential.[L39170] |
| Mechanism of Action | Polycythemia vera (PV) is the most common Philadelphia chromosome-negative myeloproliferative neoplasm (MPN), which also includes essential thrombocytopenia and myelofibrosis.[A242000, A242005] PV is characterized by increased hematocrit and platelet/leukocyte counts, an increased risk for hemorrhage and thromboembolic events, and a long-term propensity for myelofibrosis and leukemia. The main driver mutation, _JAK2_ V617F, is present in >95% of PV patients and results in constitutive JAK/STAT signalling; other exon 12 mutations in _JAK2_ may also result in PV. PV results in clonal hematopoietic stem cells, such that they form endogenous erythroid colonies (EECs) _in vitro_.[A242000] Interferon alfa-2b has been used for decades in PV despite the lack of formal approval.[A242005] Although the mechanism of action is unclear, interferon alfa-2b is known to bind the interferon-alpha/beta receptor (IFNAR) and activate downstream JAK/STAT signalling.[A242005, L39170] The overall result is a series of anti-proliferative, anti-angiogenic, pro-apoptotic, and immunomodulatory effects, including augmenting T-cell, macrophage, and natural killer cells.[A242005] Interestingly, _in vitro_ studies have revealed that ropeginterferon alfa-2b is specific to some extent for _JAK2_-mutant EECs, a result that is in line with the reduced allelic burden observed in clinical trials.[A242010, A242015] Partial and complete molecular and hematological responses have been achieved with ropeginterferon alfa-2b.[A242015] |
| Toxicity | Ropeginterferon alfa-2b overdose may present with influenza-like symptoms or other adverse reactions. As there is no known antidote, symptomatic and supportive care should be administered in the result of an overdose. Ropeginterferon alfa-2b is not mutagenic in standard assays but has not been tested for carcinogenic potential.[L39170] |
| Metabolism | Ropeginterferon alfa-2b is expected to be catabolized by various proteolytic enzymes.[L15811] |
| Absorption | In patients with polycythemia vera on a two-week dosing interval, the estimated steady-state Cmin was 1.4-12 ng/mL, Cmax was 4.4-31 ng/mL, and AUC was 1011-7809 ng |
| Ropeginterferon alfa-2b has an estimated geometric mean apparent volume of distribution (%CV) of 4.8 L (21%) in polycythemia vera patients.[L39170] | |
| Clearance | Ropeginterferon alfa-2b administered to polycythemia vera patients over a dose range of 100-500 µg has a clearance of 1.7-2.5 L/h.[L39170] |
| Categories | Alfa Interferons |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Interferon alpha/beta receptor (IFNAR) |
| Brand Name | Besremi |
| Company | Aop Orphan Pharmaceuticals Gmb H |
| Brand Description | Aop Orphan Pharmaceuticals Gmb H |
| Prescribed For | Subcutaneous |
| Chemical Name | 250 ?g/0.5ml |
| Formulation | BESREMi is contraindicated in patients with: Existence of, or history of severe psychiatric disorders, particularly severe depression, suicidal ideation, or suicide attempt Hypersensitivity to interferons including interferon alfa-2b or any of the inactive ingredients of BESREMi. Moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment History or presence of active serious or untreated autoimmune disease Immunosuppressed transplant recipients |
| Physical Appearance | influenza-like illness, joint pain, fatigue, itching, runny or stuffy nose, musculoskeletal pain, headache, diarrhea, increased sweating, nausea, upper respiratory tract infection, local administration site reactions, dizziness, abdominal pain, depression, sleep problems (insomnia, abnormal dreams), low white blood cell count (leukopenia, neutropenia), decreased appetite, hair loss, fluid retention (edema), high blood pressure (hypertension), muscle spasms, rash, transaminase elevations, urinary tract infection (UTI), low blood platelets (thrombocytopenia), and spinning sensation (vertigo). |
| Route of Administration | Besremi is a prescription medicine that is used to treat adults with polycythemia vera. It is not known if this medicine is safe and effective in children. Important information Besremi can cause serious side effects that: may cause death, or may worsen certain serious diseases that you may already have... |
| Recommended Dosage | Besremi is a prescription medicine used to treat the symptoms of Polycythemia Vera. Besremi may be used alone or with other medications. |
| Contraindication | (2S)-1-[3,7-bis(2-methoxyethoxycarbonylamino)heptyl]pyrrolidine-2-carboxylic acid |
| Side Effects | Ropeginterferon alfa-2b-njft, an interferon alfa-2b, is an N-terminal monopegylated covalent conjugate of proline interferon alfa-2b, produced in Escherichia coli cells by recombinant DNA technology, with a methoxy polyethylene glycol (mPEG) moiety. Ropeginterferon alfa-2b-njft has an approximate molecular weight of 60 kDa and the approximate molecular weight of the PEG portion of the molecule is 40 kDa. |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 15756 |
| Therapeutic ID | Th1624 |
| Protein Name | Ropeginterferon alfa-2b |
| Sequence | >Th1624_Ropeginterferon_alfa-2b PCDLPQTHSLGSRRTLMLLAQMRRISLFSCLKDRHDFGFPQEEFGNQFQKAETIPVLHEMIQQIFNLFSTKDSSAAWDETLLDKFYTELYQQLNDLEACVIQGVGVTETPLMKEDSILAVRKYFQRITLYLKEKKYSPCAWEVVRAEIMRSFSLSTNLQESLRSKE |
| Molecular Weight | 60000 |
| Chemical Formula | C16H29N3O6(C2H4O)n(C2H4O)n |
| Isoelectric Point | NA |
| Hydrophobicity | NA |
| Melting point | NA |
| Half-life | Ropeginterferon alfa-2b administered to polycythemia vera patients over a dose range of 100-500 µg has a half-life of approximately seven days.[L39170] |
| Description | Polycythemia vera (PV) is the most common Philadelphia chromosome-negative myeloproliferative neoplasm (MPN), characterized by increased hematocrit and platelet/leukocyte counts, an increased risk for hemorrhage and thromboembolic events, and a long-term propensity for myelofibrosis and leukemia.[A242000, A242005] [Interferon alfa-2b] has been used for decades to treat PV but requires frequent dosing and is not tolerated by all patients.[A242005] Ropeginterferon alfa-2b is a next-generation mono-pegylated type I interferon produced from proline-IFN-a-2b in _Escherichia coli_ that has high tolerability and a long half-life.[A242015, L39170] Ropeginterferon alfa-2b has shown efficacy in PV in _in vitro_ and _in vivo_ models and clinical trials.[A242010, A242015] Ropeginterferon alfa-2b was approved by the FDA on November 12, 2021, and is currently marketed under the trademark BESREMi by PharmaEssentia Corporation.[L39170] |
| Indication/Disease | Ropeginterferon alfa-2b is indicated for the treatment of adult patients with polycythemia vera.[L39170] |
| Pharmacodynamics | Ropeginterferon alfa-2b acts through the interferon-alpha/beta receptor to initiate downstream JAK/STAT signalling leading to its therapeutic effects. Like other interferon alfa products, ropeginterferon alfa-2b may cause various toxicities, including endocrine, cardiovascular, pulmonary, ophthalmologic, dental/periodontal, renal, and dermatological toxicity. In addition, interferon alfa has been associated with hepatotoxicity, including increases in serum ALT, AST, GGT, and bilirubin; ropeginterferon alfa-2b is contraindicated in patients with moderate to severe (Child-Pugh B or C) hepatic impairment. Pancreatitis and colitis, including fatal ulcerative/hemorrhagic/ischemic colitis, have occurred in patients treated with interferon alfa. Significant toxicity of any kind may require treatment discontinuation. Interferon alfa treatment has decreased peripheral blood counts, including thrombocytopenia and leukopenia, and altered lipid levels, including hyperlipidemia, hypertriglyceridemia, and dyslipidemia. Hypersensitivity reactions, including anaphylaxis, may occur; ropeginterferon alfa-2b is contraindicated in hypersensitive patients and those with known hypersensitivity to other interferons. Life-threatening or fatal neuropsychiatric reactions may occur, including in patients without prior history; ropeginterferon alfa-2b is contraindicated in patients with a history of severe psychiatric disorders. Finally, ropeginterferon alfa-2b can cause fetal harm and should be used with caution in females of reproductive potential.[L39170] |
| Mechanism of Action | Polycythemia vera (PV) is the most common Philadelphia chromosome-negative myeloproliferative neoplasm (MPN), which also includes essential thrombocytopenia and myelofibrosis.[A242000, A242005] PV is characterized by increased hematocrit and platelet/leukocyte counts, an increased risk for hemorrhage and thromboembolic events, and a long-term propensity for myelofibrosis and leukemia. The main driver mutation, _JAK2_ V617F, is present in >95% of PV patients and results in constitutive JAK/STAT signalling; other exon 12 mutations in _JAK2_ may also result in PV. PV results in clonal hematopoietic stem cells, such that they form endogenous erythroid colonies (EECs) _in vitro_.[A242000] Interferon alfa-2b has been used for decades in PV despite the lack of formal approval.[A242005] Although the mechanism of action is unclear, interferon alfa-2b is known to bind the interferon-alpha/beta receptor (IFNAR) and activate downstream JAK/STAT signalling.[A242005, L39170] The overall result is a series of anti-proliferative, anti-angiogenic, pro-apoptotic, and immunomodulatory effects, including augmenting T-cell, macrophage, and natural killer cells.[A242005] Interestingly, _in vitro_ studies have revealed that ropeginterferon alfa-2b is specific to some extent for _JAK2_-mutant EECs, a result that is in line with the reduced allelic burden observed in clinical trials.[A242010, A242015] Partial and complete molecular and hematological responses have been achieved with ropeginterferon alfa-2b.[A242015] |
| Toxicity | Ropeginterferon alfa-2b overdose may present with influenza-like symptoms or other adverse reactions. As there is no known antidote, symptomatic and supportive care should be administered in the result of an overdose. Ropeginterferon alfa-2b is not mutagenic in standard assays but has not been tested for carcinogenic potential.[L39170] |
| Metabolism | Ropeginterferon alfa-2b is expected to be catabolized by various proteolytic enzymes.[L15811] |
| Absorption | In patients with polycythemia vera on a two-week dosing interval, the estimated steady-state Cmin was 1.4-12 ng/mL, Cmax was 4.4-31 ng/mL, and AUC was 1011-7809 ng |
| Ropeginterferon alfa-2b has an estimated geometric mean apparent volume of distribution (%CV) of 4.8 L (21%) in polycythemia vera patients.[L39170] | |
| Clearance | Ropeginterferon alfa-2b administered to polycythemia vera patients over a dose range of 100-500 µg has a clearance of 1.7-2.5 L/h.[L39170] |
| Categories | Antineoplastic and Immunomodulating Agents |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Interferon alpha/beta receptor (IFNAR) |
| Brand Name | Besremi |
| Company | Aop Orphan Pharmaceuticals Gmb H |
| Brand Description | Aop Orphan Pharmaceuticals Gmb H |
| Prescribed For | Subcutaneous |
| Chemical Name | 500 ?g/0.5ml |
| Formulation | BESREMi is contraindicated in patients with: Existence of, or history of severe psychiatric disorders, particularly severe depression, suicidal ideation, or suicide attempt Hypersensitivity to interferons including interferon alfa-2b or any of the inactive ingredients of BESREMi. Moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment History or presence of active serious or untreated autoimmune disease Immunosuppressed transplant recipients |
| Physical Appearance | influenza-like illness, joint pain, fatigue, itching, runny or stuffy nose, musculoskeletal pain, headache, diarrhea, increased sweating, nausea, upper respiratory tract infection, local administration site reactions, dizziness, abdominal pain, depression, sleep problems (insomnia, abnormal dreams), low white blood cell count (leukopenia, neutropenia), decreased appetite, hair loss, fluid retention (edema), high blood pressure (hypertension), muscle spasms, rash, transaminase elevations, urinary tract infection (UTI), low blood platelets (thrombocytopenia), and spinning sensation (vertigo). |
| Route of Administration | Besremi is a prescription medicine that is used to treat adults with polycythemia vera. It is not known if this medicine is safe and effective in children. Important information Besremi can cause serious side effects that: may cause death, or may worsen certain serious diseases that you may already have... |
| Recommended Dosage | Besremi is a prescription medicine used to treat the symptoms of Polycythemia Vera. Besremi may be used alone or with other medications. |
| Contraindication | (2S)-1-[3,7-bis(2-methoxyethoxycarbonylamino)heptyl]pyrrolidine-2-carboxylic acid |
| Side Effects | Ropeginterferon alfa-2b-njft, an interferon alfa-2b, is an N-terminal monopegylated covalent conjugate of proline interferon alfa-2b, produced in Escherichia coli cells by recombinant DNA technology, with a methoxy polyethylene glycol (mPEG) moiety. Ropeginterferon alfa-2b-njft has an approximate molecular weight of 60 kDa and the approximate molecular weight of the PEG portion of the molecule is 40 kDa. |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 15757 |
| Therapeutic ID | Th1624 |
| Protein Name | Ropeginterferon alfa-2b |
| Sequence | >Th1624_Ropeginterferon_alfa-2b PCDLPQTHSLGSRRTLMLLAQMRRISLFSCLKDRHDFGFPQEEFGNQFQKAETIPVLHEMIQQIFNLFSTKDSSAAWDETLLDKFYTELYQQLNDLEACVIQGVGVTETPLMKEDSILAVRKYFQRITLYLKEKKYSPCAWEVVRAEIMRSFSLSTNLQESLRSKE |
| Molecular Weight | 60000 |
| Chemical Formula | C16H29N3O6(C2H4O)n(C2H4O)n |
| Isoelectric Point | NA |
| Hydrophobicity | NA |
| Melting point | NA |
| Half-life | Ropeginterferon alfa-2b administered to polycythemia vera patients over a dose range of 100-500 µg has a half-life of approximately seven days.[L39170] |
| Description | Polycythemia vera (PV) is the most common Philadelphia chromosome-negative myeloproliferative neoplasm (MPN), characterized by increased hematocrit and platelet/leukocyte counts, an increased risk for hemorrhage and thromboembolic events, and a long-term propensity for myelofibrosis and leukemia.[A242000, A242005] [Interferon alfa-2b] has been used for decades to treat PV but requires frequent dosing and is not tolerated by all patients.[A242005] Ropeginterferon alfa-2b is a next-generation mono-pegylated type I interferon produced from proline-IFN-a-2b in _Escherichia coli_ that has high tolerability and a long half-life.[A242015, L39170] Ropeginterferon alfa-2b has shown efficacy in PV in _in vitro_ and _in vivo_ models and clinical trials.[A242010, A242015] Ropeginterferon alfa-2b was approved by the FDA on November 12, 2021, and is currently marketed under the trademark BESREMi by PharmaEssentia Corporation.[L39170] |
| Indication/Disease | Ropeginterferon alfa-2b is indicated for the treatment of adult patients with polycythemia vera.[L39170] |
| Pharmacodynamics | Ropeginterferon alfa-2b acts through the interferon-alpha/beta receptor to initiate downstream JAK/STAT signalling leading to its therapeutic effects. Like other interferon alfa products, ropeginterferon alfa-2b may cause various toxicities, including endocrine, cardiovascular, pulmonary, ophthalmologic, dental/periodontal, renal, and dermatological toxicity. In addition, interferon alfa has been associated with hepatotoxicity, including increases in serum ALT, AST, GGT, and bilirubin; ropeginterferon alfa-2b is contraindicated in patients with moderate to severe (Child-Pugh B or C) hepatic impairment. Pancreatitis and colitis, including fatal ulcerative/hemorrhagic/ischemic colitis, have occurred in patients treated with interferon alfa. Significant toxicity of any kind may require treatment discontinuation. Interferon alfa treatment has decreased peripheral blood counts, including thrombocytopenia and leukopenia, and altered lipid levels, including hyperlipidemia, hypertriglyceridemia, and dyslipidemia. Hypersensitivity reactions, including anaphylaxis, may occur; ropeginterferon alfa-2b is contraindicated in hypersensitive patients and those with known hypersensitivity to other interferons. Life-threatening or fatal neuropsychiatric reactions may occur, including in patients without prior history; ropeginterferon alfa-2b is contraindicated in patients with a history of severe psychiatric disorders. Finally, ropeginterferon alfa-2b can cause fetal harm and should be used with caution in females of reproductive potential.[L39170] |
| Mechanism of Action | Polycythemia vera (PV) is the most common Philadelphia chromosome-negative myeloproliferative neoplasm (MPN), which also includes essential thrombocytopenia and myelofibrosis.[A242000, A242005] PV is characterized by increased hematocrit and platelet/leukocyte counts, an increased risk for hemorrhage and thromboembolic events, and a long-term propensity for myelofibrosis and leukemia. The main driver mutation, _JAK2_ V617F, is present in >95% of PV patients and results in constitutive JAK/STAT signalling; other exon 12 mutations in _JAK2_ may also result in PV. PV results in clonal hematopoietic stem cells, such that they form endogenous erythroid colonies (EECs) _in vitro_.[A242000] Interferon alfa-2b has been used for decades in PV despite the lack of formal approval.[A242005] Although the mechanism of action is unclear, interferon alfa-2b is known to bind the interferon-alpha/beta receptor (IFNAR) and activate downstream JAK/STAT signalling.[A242005, L39170] The overall result is a series of anti-proliferative, anti-angiogenic, pro-apoptotic, and immunomodulatory effects, including augmenting T-cell, macrophage, and natural killer cells.[A242005] Interestingly, _in vitro_ studies have revealed that ropeginterferon alfa-2b is specific to some extent for _JAK2_-mutant EECs, a result that is in line with the reduced allelic burden observed in clinical trials.[A242010, A242015] Partial and complete molecular and hematological responses have been achieved with ropeginterferon alfa-2b.[A242015] |
| Toxicity | Ropeginterferon alfa-2b overdose may present with influenza-like symptoms or other adverse reactions. As there is no known antidote, symptomatic and supportive care should be administered in the result of an overdose. Ropeginterferon alfa-2b is not mutagenic in standard assays but has not been tested for carcinogenic potential.[L39170] |
| Metabolism | Ropeginterferon alfa-2b is expected to be catabolized by various proteolytic enzymes.[L15811] |
| Absorption | In patients with polycythemia vera on a two-week dosing interval, the estimated steady-state Cmin was 1.4-12 ng/mL, Cmax was 4.4-31 ng/mL, and AUC was 1011-7809 ng |
| Ropeginterferon alfa-2b has an estimated geometric mean apparent volume of distribution (%CV) of 4.8 L (21%) in polycythemia vera patients.[L39170] | |
| Clearance | Ropeginterferon alfa-2b administered to polycythemia vera patients over a dose range of 100-500 µg has a clearance of 1.7-2.5 L/h.[L39170] |
| Categories | Cancer immunotherapy |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Interferon alpha/beta receptor (IFNAR) |
| Brand Name | NA |
| Company | NA |
| Brand Description | NA |
| Prescribed For | NA |
| Chemical Name | NA |
| Formulation | NA |
| Physical Appearance | NA |
| Route of Administration | NA |
| Recommended Dosage | NA |
| Contraindication | (2S)-1-[3,7-bis(2-methoxyethoxycarbonylamino)heptyl]pyrrolidine-2-carboxylic acid |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | NA |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 15758 |
| Therapeutic ID | Th1624 |
| Protein Name | Ropeginterferon alfa-2b |
| Sequence | >Th1624_Ropeginterferon_alfa-2b PCDLPQTHSLGSRRTLMLLAQMRRISLFSCLKDRHDFGFPQEEFGNQFQKAETIPVLHEMIQQIFNLFSTKDSSAAWDETLLDKFYTELYQQLNDLEACVIQGVGVTETPLMKEDSILAVRKYFQRITLYLKEKKYSPCAWEVVRAEIMRSFSLSTNLQESLRSKE |
| Molecular Weight | 60000 |
| Chemical Formula | C16H29N3O6(C2H4O)n(C2H4O)n |
| Isoelectric Point | NA |
| Hydrophobicity | NA |
| Melting point | NA |
| Half-life | Ropeginterferon alfa-2b administered to polycythemia vera patients over a dose range of 100-500 µg has a half-life of approximately seven days.[L39170] |
| Description | Polycythemia vera (PV) is the most common Philadelphia chromosome-negative myeloproliferative neoplasm (MPN), characterized by increased hematocrit and platelet/leukocyte counts, an increased risk for hemorrhage and thromboembolic events, and a long-term propensity for myelofibrosis and leukemia.[A242000, A242005] [Interferon alfa-2b] has been used for decades to treat PV but requires frequent dosing and is not tolerated by all patients.[A242005] Ropeginterferon alfa-2b is a next-generation mono-pegylated type I interferon produced from proline-IFN-a-2b in _Escherichia coli_ that has high tolerability and a long half-life.[A242015, L39170] Ropeginterferon alfa-2b has shown efficacy in PV in _in vitro_ and _in vivo_ models and clinical trials.[A242010, A242015] Ropeginterferon alfa-2b was approved by the FDA on November 12, 2021, and is currently marketed under the trademark BESREMi by PharmaEssentia Corporation.[L39170] |
| Indication/Disease | Ropeginterferon alfa-2b is indicated for the treatment of adult patients with polycythemia vera.[L39170] |
| Pharmacodynamics | Ropeginterferon alfa-2b acts through the interferon-alpha/beta receptor to initiate downstream JAK/STAT signalling leading to its therapeutic effects. Like other interferon alfa products, ropeginterferon alfa-2b may cause various toxicities, including endocrine, cardiovascular, pulmonary, ophthalmologic, dental/periodontal, renal, and dermatological toxicity. In addition, interferon alfa has been associated with hepatotoxicity, including increases in serum ALT, AST, GGT, and bilirubin; ropeginterferon alfa-2b is contraindicated in patients with moderate to severe (Child-Pugh B or C) hepatic impairment. Pancreatitis and colitis, including fatal ulcerative/hemorrhagic/ischemic colitis, have occurred in patients treated with interferon alfa. Significant toxicity of any kind may require treatment discontinuation. Interferon alfa treatment has decreased peripheral blood counts, including thrombocytopenia and leukopenia, and altered lipid levels, including hyperlipidemia, hypertriglyceridemia, and dyslipidemia. Hypersensitivity reactions, including anaphylaxis, may occur; ropeginterferon alfa-2b is contraindicated in hypersensitive patients and those with known hypersensitivity to other interferons. Life-threatening or fatal neuropsychiatric reactions may occur, including in patients without prior history; ropeginterferon alfa-2b is contraindicated in patients with a history of severe psychiatric disorders. Finally, ropeginterferon alfa-2b can cause fetal harm and should be used with caution in females of reproductive potential.[L39170] |
| Mechanism of Action | Polycythemia vera (PV) is the most common Philadelphia chromosome-negative myeloproliferative neoplasm (MPN), which also includes essential thrombocytopenia and myelofibrosis.[A242000, A242005] PV is characterized by increased hematocrit and platelet/leukocyte counts, an increased risk for hemorrhage and thromboembolic events, and a long-term propensity for myelofibrosis and leukemia. The main driver mutation, _JAK2_ V617F, is present in >95% of PV patients and results in constitutive JAK/STAT signalling; other exon 12 mutations in _JAK2_ may also result in PV. PV results in clonal hematopoietic stem cells, such that they form endogenous erythroid colonies (EECs) _in vitro_.[A242000] Interferon alfa-2b has been used for decades in PV despite the lack of formal approval.[A242005] Although the mechanism of action is unclear, interferon alfa-2b is known to bind the interferon-alpha/beta receptor (IFNAR) and activate downstream JAK/STAT signalling.[A242005, L39170] The overall result is a series of anti-proliferative, anti-angiogenic, pro-apoptotic, and immunomodulatory effects, including augmenting T-cell, macrophage, and natural killer cells.[A242005] Interestingly, _in vitro_ studies have revealed that ropeginterferon alfa-2b is specific to some extent for _JAK2_-mutant EECs, a result that is in line with the reduced allelic burden observed in clinical trials.[A242010, A242015] Partial and complete molecular and hematological responses have been achieved with ropeginterferon alfa-2b.[A242015] |
| Toxicity | Ropeginterferon alfa-2b overdose may present with influenza-like symptoms or other adverse reactions. As there is no known antidote, symptomatic and supportive care should be administered in the result of an overdose. Ropeginterferon alfa-2b is not mutagenic in standard assays but has not been tested for carcinogenic potential.[L39170] |
| Metabolism | Ropeginterferon alfa-2b is expected to be catabolized by various proteolytic enzymes.[L15811] |
| Absorption | In patients with polycythemia vera on a two-week dosing interval, the estimated steady-state Cmin was 1.4-12 ng/mL, Cmax was 4.4-31 ng/mL, and AUC was 1011-7809 ng |
| Ropeginterferon alfa-2b has an estimated geometric mean apparent volume of distribution (%CV) of 4.8 L (21%) in polycythemia vera patients.[L39170] | |
| Clearance | Ropeginterferon alfa-2b administered to polycythemia vera patients over a dose range of 100-500 µg has a clearance of 1.7-2.5 L/h.[L39170] |
| Categories | Cytochrome P-450 CYP1A2 Inhibitors |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Interferon alpha/beta receptor (IFNAR) |
| Brand Name | NA |
| Company | NA |
| Brand Description | NA |
| Prescribed For | NA |
| Chemical Name | NA |
| Formulation | NA |
| Physical Appearance | NA |
| Route of Administration | NA |
| Recommended Dosage | NA |
| Contraindication | (2S)-1-[3,7-bis(2-methoxyethoxycarbonylamino)heptyl]pyrrolidine-2-carboxylic acid |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | NA |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 15759 |
| Therapeutic ID | Th1624 |
| Protein Name | Ropeginterferon alfa-2b |
| Sequence | >Th1624_Ropeginterferon_alfa-2b PCDLPQTHSLGSRRTLMLLAQMRRISLFSCLKDRHDFGFPQEEFGNQFQKAETIPVLHEMIQQIFNLFSTKDSSAAWDETLLDKFYTELYQQLNDLEACVIQGVGVTETPLMKEDSILAVRKYFQRITLYLKEKKYSPCAWEVVRAEIMRSFSLSTNLQESLRSKE |
| Molecular Weight | 60000 |
| Chemical Formula | C16H29N3O6(C2H4O)n(C2H4O)n |
| Isoelectric Point | NA |
| Hydrophobicity | NA |
| Melting point | NA |
| Half-life | Ropeginterferon alfa-2b administered to polycythemia vera patients over a dose range of 100-500 µg has a half-life of approximately seven days.[L39170] |
| Description | Polycythemia vera (PV) is the most common Philadelphia chromosome-negative myeloproliferative neoplasm (MPN), characterized by increased hematocrit and platelet/leukocyte counts, an increased risk for hemorrhage and thromboembolic events, and a long-term propensity for myelofibrosis and leukemia.[A242000, A242005] [Interferon alfa-2b] has been used for decades to treat PV but requires frequent dosing and is not tolerated by all patients.[A242005] Ropeginterferon alfa-2b is a next-generation mono-pegylated type I interferon produced from proline-IFN-a-2b in _Escherichia coli_ that has high tolerability and a long half-life.[A242015, L39170] Ropeginterferon alfa-2b has shown efficacy in PV in _in vitro_ and _in vivo_ models and clinical trials.[A242010, A242015] Ropeginterferon alfa-2b was approved by the FDA on November 12, 2021, and is currently marketed under the trademark BESREMi by PharmaEssentia Corporation.[L39170] |
| Indication/Disease | Ropeginterferon alfa-2b is indicated for the treatment of adult patients with polycythemia vera.[L39170] |
| Pharmacodynamics | Ropeginterferon alfa-2b acts through the interferon-alpha/beta receptor to initiate downstream JAK/STAT signalling leading to its therapeutic effects. Like other interferon alfa products, ropeginterferon alfa-2b may cause various toxicities, including endocrine, cardiovascular, pulmonary, ophthalmologic, dental/periodontal, renal, and dermatological toxicity. In addition, interferon alfa has been associated with hepatotoxicity, including increases in serum ALT, AST, GGT, and bilirubin; ropeginterferon alfa-2b is contraindicated in patients with moderate to severe (Child-Pugh B or C) hepatic impairment. Pancreatitis and colitis, including fatal ulcerative/hemorrhagic/ischemic colitis, have occurred in patients treated with interferon alfa. Significant toxicity of any kind may require treatment discontinuation. Interferon alfa treatment has decreased peripheral blood counts, including thrombocytopenia and leukopenia, and altered lipid levels, including hyperlipidemia, hypertriglyceridemia, and dyslipidemia. Hypersensitivity reactions, including anaphylaxis, may occur; ropeginterferon alfa-2b is contraindicated in hypersensitive patients and those with known hypersensitivity to other interferons. Life-threatening or fatal neuropsychiatric reactions may occur, including in patients without prior history; ropeginterferon alfa-2b is contraindicated in patients with a history of severe psychiatric disorders. Finally, ropeginterferon alfa-2b can cause fetal harm and should be used with caution in females of reproductive potential.[L39170] |
| Mechanism of Action | Polycythemia vera (PV) is the most common Philadelphia chromosome-negative myeloproliferative neoplasm (MPN), which also includes essential thrombocytopenia and myelofibrosis.[A242000, A242005] PV is characterized by increased hematocrit and platelet/leukocyte counts, an increased risk for hemorrhage and thromboembolic events, and a long-term propensity for myelofibrosis and leukemia. The main driver mutation, _JAK2_ V617F, is present in >95% of PV patients and results in constitutive JAK/STAT signalling; other exon 12 mutations in _JAK2_ may also result in PV. PV results in clonal hematopoietic stem cells, such that they form endogenous erythroid colonies (EECs) _in vitro_.[A242000] Interferon alfa-2b has been used for decades in PV despite the lack of formal approval.[A242005] Although the mechanism of action is unclear, interferon alfa-2b is known to bind the interferon-alpha/beta receptor (IFNAR) and activate downstream JAK/STAT signalling.[A242005, L39170] The overall result is a series of anti-proliferative, anti-angiogenic, pro-apoptotic, and immunomodulatory effects, including augmenting T-cell, macrophage, and natural killer cells.[A242005] Interestingly, _in vitro_ studies have revealed that ropeginterferon alfa-2b is specific to some extent for _JAK2_-mutant EECs, a result that is in line with the reduced allelic burden observed in clinical trials.[A242010, A242015] Partial and complete molecular and hematological responses have been achieved with ropeginterferon alfa-2b.[A242015] |
| Toxicity | Ropeginterferon alfa-2b overdose may present with influenza-like symptoms or other adverse reactions. As there is no known antidote, symptomatic and supportive care should be administered in the result of an overdose. Ropeginterferon alfa-2b is not mutagenic in standard assays but has not been tested for carcinogenic potential.[L39170] |
| Metabolism | Ropeginterferon alfa-2b is expected to be catabolized by various proteolytic enzymes.[L15811] |
| Absorption | In patients with polycythemia vera on a two-week dosing interval, the estimated steady-state Cmin was 1.4-12 ng/mL, Cmax was 4.4-31 ng/mL, and AUC was 1011-7809 ng |
| Ropeginterferon alfa-2b has an estimated geometric mean apparent volume of distribution (%CV) of 4.8 L (21%) in polycythemia vera patients.[L39170] | |
| Clearance | Ropeginterferon alfa-2b administered to polycythemia vera patients over a dose range of 100-500 µg has a clearance of 1.7-2.5 L/h.[L39170] |
| Categories | Cytochrome P-450 CYP1A2 Inhibitors (strength unknown) |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Interferon alpha/beta receptor (IFNAR) |
| Brand Name | NA |
| Company | NA |
| Brand Description | NA |
| Prescribed For | NA |
| Chemical Name | NA |
| Formulation | NA |
| Physical Appearance | NA |
| Route of Administration | NA |
| Recommended Dosage | NA |
| Contraindication | (2S)-1-[3,7-bis(2-methoxyethoxycarbonylamino)heptyl]pyrrolidine-2-carboxylic acid |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | NA |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 15760 |
| Therapeutic ID | Th1624 |
| Protein Name | Ropeginterferon alfa-2b |
| Sequence | >Th1624_Ropeginterferon_alfa-2b PCDLPQTHSLGSRRTLMLLAQMRRISLFSCLKDRHDFGFPQEEFGNQFQKAETIPVLHEMIQQIFNLFSTKDSSAAWDETLLDKFYTELYQQLNDLEACVIQGVGVTETPLMKEDSILAVRKYFQRITLYLKEKKYSPCAWEVVRAEIMRSFSLSTNLQESLRSKE |
| Molecular Weight | 60000 |
| Chemical Formula | C16H29N3O6(C2H4O)n(C2H4O)n |
| Isoelectric Point | NA |
| Hydrophobicity | NA |
| Melting point | NA |
| Half-life | Ropeginterferon alfa-2b administered to polycythemia vera patients over a dose range of 100-500 µg has a half-life of approximately seven days.[L39170] |
| Description | Polycythemia vera (PV) is the most common Philadelphia chromosome-negative myeloproliferative neoplasm (MPN), characterized by increased hematocrit and platelet/leukocyte counts, an increased risk for hemorrhage and thromboembolic events, and a long-term propensity for myelofibrosis and leukemia.[A242000, A242005] [Interferon alfa-2b] has been used for decades to treat PV but requires frequent dosing and is not tolerated by all patients.[A242005] Ropeginterferon alfa-2b is a next-generation mono-pegylated type I interferon produced from proline-IFN-a-2b in _Escherichia coli_ that has high tolerability and a long half-life.[A242015, L39170] Ropeginterferon alfa-2b has shown efficacy in PV in _in vitro_ and _in vivo_ models and clinical trials.[A242010, A242015] Ropeginterferon alfa-2b was approved by the FDA on November 12, 2021, and is currently marketed under the trademark BESREMi by PharmaEssentia Corporation.[L39170] |
| Indication/Disease | Ropeginterferon alfa-2b is indicated for the treatment of adult patients with polycythemia vera.[L39170] |
| Pharmacodynamics | Ropeginterferon alfa-2b acts through the interferon-alpha/beta receptor to initiate downstream JAK/STAT signalling leading to its therapeutic effects. Like other interferon alfa products, ropeginterferon alfa-2b may cause various toxicities, including endocrine, cardiovascular, pulmonary, ophthalmologic, dental/periodontal, renal, and dermatological toxicity. In addition, interferon alfa has been associated with hepatotoxicity, including increases in serum ALT, AST, GGT, and bilirubin; ropeginterferon alfa-2b is contraindicated in patients with moderate to severe (Child-Pugh B or C) hepatic impairment. Pancreatitis and colitis, including fatal ulcerative/hemorrhagic/ischemic colitis, have occurred in patients treated with interferon alfa. Significant toxicity of any kind may require treatment discontinuation. Interferon alfa treatment has decreased peripheral blood counts, including thrombocytopenia and leukopenia, and altered lipid levels, including hyperlipidemia, hypertriglyceridemia, and dyslipidemia. Hypersensitivity reactions, including anaphylaxis, may occur; ropeginterferon alfa-2b is contraindicated in hypersensitive patients and those with known hypersensitivity to other interferons. Life-threatening or fatal neuropsychiatric reactions may occur, including in patients without prior history; ropeginterferon alfa-2b is contraindicated in patients with a history of severe psychiatric disorders. Finally, ropeginterferon alfa-2b can cause fetal harm and should be used with caution in females of reproductive potential.[L39170] |
| Mechanism of Action | Polycythemia vera (PV) is the most common Philadelphia chromosome-negative myeloproliferative neoplasm (MPN), which also includes essential thrombocytopenia and myelofibrosis.[A242000, A242005] PV is characterized by increased hematocrit and platelet/leukocyte counts, an increased risk for hemorrhage and thromboembolic events, and a long-term propensity for myelofibrosis and leukemia. The main driver mutation, _JAK2_ V617F, is present in >95% of PV patients and results in constitutive JAK/STAT signalling; other exon 12 mutations in _JAK2_ may also result in PV. PV results in clonal hematopoietic stem cells, such that they form endogenous erythroid colonies (EECs) _in vitro_.[A242000] Interferon alfa-2b has been used for decades in PV despite the lack of formal approval.[A242005] Although the mechanism of action is unclear, interferon alfa-2b is known to bind the interferon-alpha/beta receptor (IFNAR) and activate downstream JAK/STAT signalling.[A242005, L39170] The overall result is a series of anti-proliferative, anti-angiogenic, pro-apoptotic, and immunomodulatory effects, including augmenting T-cell, macrophage, and natural killer cells.[A242005] Interestingly, _in vitro_ studies have revealed that ropeginterferon alfa-2b is specific to some extent for _JAK2_-mutant EECs, a result that is in line with the reduced allelic burden observed in clinical trials.[A242010, A242015] Partial and complete molecular and hematological responses have been achieved with ropeginterferon alfa-2b.[A242015] |
| Toxicity | Ropeginterferon alfa-2b overdose may present with influenza-like symptoms or other adverse reactions. As there is no known antidote, symptomatic and supportive care should be administered in the result of an overdose. Ropeginterferon alfa-2b is not mutagenic in standard assays but has not been tested for carcinogenic potential.[L39170] |
| Metabolism | Ropeginterferon alfa-2b is expected to be catabolized by various proteolytic enzymes.[L15811] |
| Absorption | In patients with polycythemia vera on a two-week dosing interval, the estimated steady-state Cmin was 1.4-12 ng/mL, Cmax was 4.4-31 ng/mL, and AUC was 1011-7809 ng |
| Ropeginterferon alfa-2b has an estimated geometric mean apparent volume of distribution (%CV) of 4.8 L (21%) in polycythemia vera patients.[L39170] | |
| Clearance | Ropeginterferon alfa-2b administered to polycythemia vera patients over a dose range of 100-500 µg has a clearance of 1.7-2.5 L/h.[L39170] |
| Categories | Cytochrome P-450 CYP2A6 Inhibitors |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Interferon alpha/beta receptor (IFNAR) |
| Brand Name | NA |
| Company | NA |
| Brand Description | NA |
| Prescribed For | NA |
| Chemical Name | NA |
| Formulation | NA |
| Physical Appearance | NA |
| Route of Administration | NA |
| Recommended Dosage | NA |
| Contraindication | (2S)-1-[3,7-bis(2-methoxyethoxycarbonylamino)heptyl]pyrrolidine-2-carboxylic acid |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | NA |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 15761 |
| Therapeutic ID | Th1624 |
| Protein Name | Ropeginterferon alfa-2b |
| Sequence | >Th1624_Ropeginterferon_alfa-2b PCDLPQTHSLGSRRTLMLLAQMRRISLFSCLKDRHDFGFPQEEFGNQFQKAETIPVLHEMIQQIFNLFSTKDSSAAWDETLLDKFYTELYQQLNDLEACVIQGVGVTETPLMKEDSILAVRKYFQRITLYLKEKKYSPCAWEVVRAEIMRSFSLSTNLQESLRSKE |
| Molecular Weight | 60000 |
| Chemical Formula | C16H29N3O6(C2H4O)n(C2H4O)n |
| Isoelectric Point | NA |
| Hydrophobicity | NA |
| Melting point | NA |
| Half-life | Ropeginterferon alfa-2b administered to polycythemia vera patients over a dose range of 100-500 µg has a half-life of approximately seven days.[L39170] |
| Description | Polycythemia vera (PV) is the most common Philadelphia chromosome-negative myeloproliferative neoplasm (MPN), characterized by increased hematocrit and platelet/leukocyte counts, an increased risk for hemorrhage and thromboembolic events, and a long-term propensity for myelofibrosis and leukemia.[A242000, A242005] [Interferon alfa-2b] has been used for decades to treat PV but requires frequent dosing and is not tolerated by all patients.[A242005] Ropeginterferon alfa-2b is a next-generation mono-pegylated type I interferon produced from proline-IFN-a-2b in _Escherichia coli_ that has high tolerability and a long half-life.[A242015, L39170] Ropeginterferon alfa-2b has shown efficacy in PV in _in vitro_ and _in vivo_ models and clinical trials.[A242010, A242015] Ropeginterferon alfa-2b was approved by the FDA on November 12, 2021, and is currently marketed under the trademark BESREMi by PharmaEssentia Corporation.[L39170] |
| Indication/Disease | Ropeginterferon alfa-2b is indicated for the treatment of adult patients with polycythemia vera.[L39170] |
| Pharmacodynamics | Ropeginterferon alfa-2b acts through the interferon-alpha/beta receptor to initiate downstream JAK/STAT signalling leading to its therapeutic effects. Like other interferon alfa products, ropeginterferon alfa-2b may cause various toxicities, including endocrine, cardiovascular, pulmonary, ophthalmologic, dental/periodontal, renal, and dermatological toxicity. In addition, interferon alfa has been associated with hepatotoxicity, including increases in serum ALT, AST, GGT, and bilirubin; ropeginterferon alfa-2b is contraindicated in patients with moderate to severe (Child-Pugh B or C) hepatic impairment. Pancreatitis and colitis, including fatal ulcerative/hemorrhagic/ischemic colitis, have occurred in patients treated with interferon alfa. Significant toxicity of any kind may require treatment discontinuation. Interferon alfa treatment has decreased peripheral blood counts, including thrombocytopenia and leukopenia, and altered lipid levels, including hyperlipidemia, hypertriglyceridemia, and dyslipidemia. Hypersensitivity reactions, including anaphylaxis, may occur; ropeginterferon alfa-2b is contraindicated in hypersensitive patients and those with known hypersensitivity to other interferons. Life-threatening or fatal neuropsychiatric reactions may occur, including in patients without prior history; ropeginterferon alfa-2b is contraindicated in patients with a history of severe psychiatric disorders. Finally, ropeginterferon alfa-2b can cause fetal harm and should be used with caution in females of reproductive potential.[L39170] |
| Mechanism of Action | Polycythemia vera (PV) is the most common Philadelphia chromosome-negative myeloproliferative neoplasm (MPN), which also includes essential thrombocytopenia and myelofibrosis.[A242000, A242005] PV is characterized by increased hematocrit and platelet/leukocyte counts, an increased risk for hemorrhage and thromboembolic events, and a long-term propensity for myelofibrosis and leukemia. The main driver mutation, _JAK2_ V617F, is present in >95% of PV patients and results in constitutive JAK/STAT signalling; other exon 12 mutations in _JAK2_ may also result in PV. PV results in clonal hematopoietic stem cells, such that they form endogenous erythroid colonies (EECs) _in vitro_.[A242000] Interferon alfa-2b has been used for decades in PV despite the lack of formal approval.[A242005] Although the mechanism of action is unclear, interferon alfa-2b is known to bind the interferon-alpha/beta receptor (IFNAR) and activate downstream JAK/STAT signalling.[A242005, L39170] The overall result is a series of anti-proliferative, anti-angiogenic, pro-apoptotic, and immunomodulatory effects, including augmenting T-cell, macrophage, and natural killer cells.[A242005] Interestingly, _in vitro_ studies have revealed that ropeginterferon alfa-2b is specific to some extent for _JAK2_-mutant EECs, a result that is in line with the reduced allelic burden observed in clinical trials.[A242010, A242015] Partial and complete molecular and hematological responses have been achieved with ropeginterferon alfa-2b.[A242015] |
| Toxicity | Ropeginterferon alfa-2b overdose may present with influenza-like symptoms or other adverse reactions. As there is no known antidote, symptomatic and supportive care should be administered in the result of an overdose. Ropeginterferon alfa-2b is not mutagenic in standard assays but has not been tested for carcinogenic potential.[L39170] |
| Metabolism | Ropeginterferon alfa-2b is expected to be catabolized by various proteolytic enzymes.[L15811] |
| Absorption | In patients with polycythemia vera on a two-week dosing interval, the estimated steady-state Cmin was 1.4-12 ng/mL, Cmax was 4.4-31 ng/mL, and AUC was 1011-7809 ng |
| Ropeginterferon alfa-2b has an estimated geometric mean apparent volume of distribution (%CV) of 4.8 L (21%) in polycythemia vera patients.[L39170] | |
| Clearance | Ropeginterferon alfa-2b administered to polycythemia vera patients over a dose range of 100-500 µg has a clearance of 1.7-2.5 L/h.[L39170] |
| Categories | Cytochrome P-450 CYP2A6 Inhibitors (strength unknown) |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Interferon alpha/beta receptor (IFNAR) |
| Brand Name | NA |
| Company | NA |
| Brand Description | NA |
| Prescribed For | NA |
| Chemical Name | NA |
| Formulation | NA |
| Physical Appearance | NA |
| Route of Administration | NA |
| Recommended Dosage | NA |
| Contraindication | (2S)-1-[3,7-bis(2-methoxyethoxycarbonylamino)heptyl]pyrrolidine-2-carboxylic acid |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | NA |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 15762 |
| Therapeutic ID | Th1624 |
| Protein Name | Ropeginterferon alfa-2b |
| Sequence | >Th1624_Ropeginterferon_alfa-2b PCDLPQTHSLGSRRTLMLLAQMRRISLFSCLKDRHDFGFPQEEFGNQFQKAETIPVLHEMIQQIFNLFSTKDSSAAWDETLLDKFYTELYQQLNDLEACVIQGVGVTETPLMKEDSILAVRKYFQRITLYLKEKKYSPCAWEVVRAEIMRSFSLSTNLQESLRSKE |
| Molecular Weight | 60000 |
| Chemical Formula | C16H29N3O6(C2H4O)n(C2H4O)n |
| Isoelectric Point | NA |
| Hydrophobicity | NA |
| Melting point | NA |
| Half-life | Ropeginterferon alfa-2b administered to polycythemia vera patients over a dose range of 100-500 µg has a half-life of approximately seven days.[L39170] |
| Description | Polycythemia vera (PV) is the most common Philadelphia chromosome-negative myeloproliferative neoplasm (MPN), characterized by increased hematocrit and platelet/leukocyte counts, an increased risk for hemorrhage and thromboembolic events, and a long-term propensity for myelofibrosis and leukemia.[A242000, A242005] [Interferon alfa-2b] has been used for decades to treat PV but requires frequent dosing and is not tolerated by all patients.[A242005] Ropeginterferon alfa-2b is a next-generation mono-pegylated type I interferon produced from proline-IFN-a-2b in _Escherichia coli_ that has high tolerability and a long half-life.[A242015, L39170] Ropeginterferon alfa-2b has shown efficacy in PV in _in vitro_ and _in vivo_ models and clinical trials.[A242010, A242015] Ropeginterferon alfa-2b was approved by the FDA on November 12, 2021, and is currently marketed under the trademark BESREMi by PharmaEssentia Corporation.[L39170] |
| Indication/Disease | Ropeginterferon alfa-2b is indicated for the treatment of adult patients with polycythemia vera.[L39170] |
| Pharmacodynamics | Ropeginterferon alfa-2b acts through the interferon-alpha/beta receptor to initiate downstream JAK/STAT signalling leading to its therapeutic effects. Like other interferon alfa products, ropeginterferon alfa-2b may cause various toxicities, including endocrine, cardiovascular, pulmonary, ophthalmologic, dental/periodontal, renal, and dermatological toxicity. In addition, interferon alfa has been associated with hepatotoxicity, including increases in serum ALT, AST, GGT, and bilirubin; ropeginterferon alfa-2b is contraindicated in patients with moderate to severe (Child-Pugh B or C) hepatic impairment. Pancreatitis and colitis, including fatal ulcerative/hemorrhagic/ischemic colitis, have occurred in patients treated with interferon alfa. Significant toxicity of any kind may require treatment discontinuation. Interferon alfa treatment has decreased peripheral blood counts, including thrombocytopenia and leukopenia, and altered lipid levels, including hyperlipidemia, hypertriglyceridemia, and dyslipidemia. Hypersensitivity reactions, including anaphylaxis, may occur; ropeginterferon alfa-2b is contraindicated in hypersensitive patients and those with known hypersensitivity to other interferons. Life-threatening or fatal neuropsychiatric reactions may occur, including in patients without prior history; ropeginterferon alfa-2b is contraindicated in patients with a history of severe psychiatric disorders. Finally, ropeginterferon alfa-2b can cause fetal harm and should be used with caution in females of reproductive potential.[L39170] |
| Mechanism of Action | Polycythemia vera (PV) is the most common Philadelphia chromosome-negative myeloproliferative neoplasm (MPN), which also includes essential thrombocytopenia and myelofibrosis.[A242000, A242005] PV is characterized by increased hematocrit and platelet/leukocyte counts, an increased risk for hemorrhage and thromboembolic events, and a long-term propensity for myelofibrosis and leukemia. The main driver mutation, _JAK2_ V617F, is present in >95% of PV patients and results in constitutive JAK/STAT signalling; other exon 12 mutations in _JAK2_ may also result in PV. PV results in clonal hematopoietic stem cells, such that they form endogenous erythroid colonies (EECs) _in vitro_.[A242000] Interferon alfa-2b has been used for decades in PV despite the lack of formal approval.[A242005] Although the mechanism of action is unclear, interferon alfa-2b is known to bind the interferon-alpha/beta receptor (IFNAR) and activate downstream JAK/STAT signalling.[A242005, L39170] The overall result is a series of anti-proliferative, anti-angiogenic, pro-apoptotic, and immunomodulatory effects, including augmenting T-cell, macrophage, and natural killer cells.[A242005] Interestingly, _in vitro_ studies have revealed that ropeginterferon alfa-2b is specific to some extent for _JAK2_-mutant EECs, a result that is in line with the reduced allelic burden observed in clinical trials.[A242010, A242015] Partial and complete molecular and hematological responses have been achieved with ropeginterferon alfa-2b.[A242015] |
| Toxicity | Ropeginterferon alfa-2b overdose may present with influenza-like symptoms or other adverse reactions. As there is no known antidote, symptomatic and supportive care should be administered in the result of an overdose. Ropeginterferon alfa-2b is not mutagenic in standard assays but has not been tested for carcinogenic potential.[L39170] |
| Metabolism | Ropeginterferon alfa-2b is expected to be catabolized by various proteolytic enzymes.[L15811] |
| Absorption | In patients with polycythemia vera on a two-week dosing interval, the estimated steady-state Cmin was 1.4-12 ng/mL, Cmax was 4.4-31 ng/mL, and AUC was 1011-7809 ng |
| Ropeginterferon alfa-2b has an estimated geometric mean apparent volume of distribution (%CV) of 4.8 L (21%) in polycythemia vera patients.[L39170] | |
| Clearance | Ropeginterferon alfa-2b administered to polycythemia vera patients over a dose range of 100-500 µg has a clearance of 1.7-2.5 L/h.[L39170] |
| Categories | Cytochrome P-450 CYP2D6 Inhibitors |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Interferon alpha/beta receptor (IFNAR) |
| Brand Name | NA |
| Company | NA |
| Brand Description | NA |
| Prescribed For | NA |
| Chemical Name | NA |
| Formulation | NA |
| Physical Appearance | NA |
| Route of Administration | NA |
| Recommended Dosage | NA |
| Contraindication | (2S)-1-[3,7-bis(2-methoxyethoxycarbonylamino)heptyl]pyrrolidine-2-carboxylic acid |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | NA |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 15763 |
| Therapeutic ID | Th1624 |
| Protein Name | Ropeginterferon alfa-2b |
| Sequence | >Th1624_Ropeginterferon_alfa-2b PCDLPQTHSLGSRRTLMLLAQMRRISLFSCLKDRHDFGFPQEEFGNQFQKAETIPVLHEMIQQIFNLFSTKDSSAAWDETLLDKFYTELYQQLNDLEACVIQGVGVTETPLMKEDSILAVRKYFQRITLYLKEKKYSPCAWEVVRAEIMRSFSLSTNLQESLRSKE |
| Molecular Weight | 60000 |
| Chemical Formula | C16H29N3O6(C2H4O)n(C2H4O)n |
| Isoelectric Point | NA |
| Hydrophobicity | NA |
| Melting point | NA |
| Half-life | Ropeginterferon alfa-2b administered to polycythemia vera patients over a dose range of 100-500 µg has a half-life of approximately seven days.[L39170] |
| Description | Polycythemia vera (PV) is the most common Philadelphia chromosome-negative myeloproliferative neoplasm (MPN), characterized by increased hematocrit and platelet/leukocyte counts, an increased risk for hemorrhage and thromboembolic events, and a long-term propensity for myelofibrosis and leukemia.[A242000, A242005] [Interferon alfa-2b] has been used for decades to treat PV but requires frequent dosing and is not tolerated by all patients.[A242005] Ropeginterferon alfa-2b is a next-generation mono-pegylated type I interferon produced from proline-IFN-a-2b in _Escherichia coli_ that has high tolerability and a long half-life.[A242015, L39170] Ropeginterferon alfa-2b has shown efficacy in PV in _in vitro_ and _in vivo_ models and clinical trials.[A242010, A242015] Ropeginterferon alfa-2b was approved by the FDA on November 12, 2021, and is currently marketed under the trademark BESREMi by PharmaEssentia Corporation.[L39170] |
| Indication/Disease | Ropeginterferon alfa-2b is indicated for the treatment of adult patients with polycythemia vera.[L39170] |
| Pharmacodynamics | Ropeginterferon alfa-2b acts through the interferon-alpha/beta receptor to initiate downstream JAK/STAT signalling leading to its therapeutic effects. Like other interferon alfa products, ropeginterferon alfa-2b may cause various toxicities, including endocrine, cardiovascular, pulmonary, ophthalmologic, dental/periodontal, renal, and dermatological toxicity. In addition, interferon alfa has been associated with hepatotoxicity, including increases in serum ALT, AST, GGT, and bilirubin; ropeginterferon alfa-2b is contraindicated in patients with moderate to severe (Child-Pugh B or C) hepatic impairment. Pancreatitis and colitis, including fatal ulcerative/hemorrhagic/ischemic colitis, have occurred in patients treated with interferon alfa. Significant toxicity of any kind may require treatment discontinuation. Interferon alfa treatment has decreased peripheral blood counts, including thrombocytopenia and leukopenia, and altered lipid levels, including hyperlipidemia, hypertriglyceridemia, and dyslipidemia. Hypersensitivity reactions, including anaphylaxis, may occur; ropeginterferon alfa-2b is contraindicated in hypersensitive patients and those with known hypersensitivity to other interferons. Life-threatening or fatal neuropsychiatric reactions may occur, including in patients without prior history; ropeginterferon alfa-2b is contraindicated in patients with a history of severe psychiatric disorders. Finally, ropeginterferon alfa-2b can cause fetal harm and should be used with caution in females of reproductive potential.[L39170] |
| Mechanism of Action | Polycythemia vera (PV) is the most common Philadelphia chromosome-negative myeloproliferative neoplasm (MPN), which also includes essential thrombocytopenia and myelofibrosis.[A242000, A242005] PV is characterized by increased hematocrit and platelet/leukocyte counts, an increased risk for hemorrhage and thromboembolic events, and a long-term propensity for myelofibrosis and leukemia. The main driver mutation, _JAK2_ V617F, is present in >95% of PV patients and results in constitutive JAK/STAT signalling; other exon 12 mutations in _JAK2_ may also result in PV. PV results in clonal hematopoietic stem cells, such that they form endogenous erythroid colonies (EECs) _in vitro_.[A242000] Interferon alfa-2b has been used for decades in PV despite the lack of formal approval.[A242005] Although the mechanism of action is unclear, interferon alfa-2b is known to bind the interferon-alpha/beta receptor (IFNAR) and activate downstream JAK/STAT signalling.[A242005, L39170] The overall result is a series of anti-proliferative, anti-angiogenic, pro-apoptotic, and immunomodulatory effects, including augmenting T-cell, macrophage, and natural killer cells.[A242005] Interestingly, _in vitro_ studies have revealed that ropeginterferon alfa-2b is specific to some extent for _JAK2_-mutant EECs, a result that is in line with the reduced allelic burden observed in clinical trials.[A242010, A242015] Partial and complete molecular and hematological responses have been achieved with ropeginterferon alfa-2b.[A242015] |
| Toxicity | Ropeginterferon alfa-2b overdose may present with influenza-like symptoms or other adverse reactions. As there is no known antidote, symptomatic and supportive care should be administered in the result of an overdose. Ropeginterferon alfa-2b is not mutagenic in standard assays but has not been tested for carcinogenic potential.[L39170] |
| Metabolism | Ropeginterferon alfa-2b is expected to be catabolized by various proteolytic enzymes.[L15811] |
| Absorption | In patients with polycythemia vera on a two-week dosing interval, the estimated steady-state Cmin was 1.4-12 ng/mL, Cmax was 4.4-31 ng/mL, and AUC was 1011-7809 ng |
| Ropeginterferon alfa-2b has an estimated geometric mean apparent volume of distribution (%CV) of 4.8 L (21%) in polycythemia vera patients.[L39170] | |
| Clearance | Ropeginterferon alfa-2b administered to polycythemia vera patients over a dose range of 100-500 µg has a clearance of 1.7-2.5 L/h.[L39170] |
| Categories | Cytochrome P-450 CYP2D6 Inhibitors (strength unknown) |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Interferon alpha/beta receptor (IFNAR) |
| Brand Name | NA |
| Company | NA |
| Brand Description | NA |
| Prescribed For | NA |
| Chemical Name | NA |
| Formulation | NA |
| Physical Appearance | NA |
| Route of Administration | NA |
| Recommended Dosage | NA |
| Contraindication | (2S)-1-[3,7-bis(2-methoxyethoxycarbonylamino)heptyl]pyrrolidine-2-carboxylic acid |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | NA |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 15764 |
| Therapeutic ID | Th1624 |
| Protein Name | Ropeginterferon alfa-2b |
| Sequence | >Th1624_Ropeginterferon_alfa-2b PCDLPQTHSLGSRRTLMLLAQMRRISLFSCLKDRHDFGFPQEEFGNQFQKAETIPVLHEMIQQIFNLFSTKDSSAAWDETLLDKFYTELYQQLNDLEACVIQGVGVTETPLMKEDSILAVRKYFQRITLYLKEKKYSPCAWEVVRAEIMRSFSLSTNLQESLRSKE |
| Molecular Weight | 60000 |
| Chemical Formula | C16H29N3O6(C2H4O)n(C2H4O)n |
| Isoelectric Point | NA |
| Hydrophobicity | NA |
| Melting point | NA |
| Half-life | Ropeginterferon alfa-2b administered to polycythemia vera patients over a dose range of 100-500 µg has a half-life of approximately seven days.[L39170] |
| Description | Polycythemia vera (PV) is the most common Philadelphia chromosome-negative myeloproliferative neoplasm (MPN), characterized by increased hematocrit and platelet/leukocyte counts, an increased risk for hemorrhage and thromboembolic events, and a long-term propensity for myelofibrosis and leukemia.[A242000, A242005] [Interferon alfa-2b] has been used for decades to treat PV but requires frequent dosing and is not tolerated by all patients.[A242005] Ropeginterferon alfa-2b is a next-generation mono-pegylated type I interferon produced from proline-IFN-a-2b in _Escherichia coli_ that has high tolerability and a long half-life.[A242015, L39170] Ropeginterferon alfa-2b has shown efficacy in PV in _in vitro_ and _in vivo_ models and clinical trials.[A242010, A242015] Ropeginterferon alfa-2b was approved by the FDA on November 12, 2021, and is currently marketed under the trademark BESREMi by PharmaEssentia Corporation.[L39170] |
| Indication/Disease | Ropeginterferon alfa-2b is indicated for the treatment of adult patients with polycythemia vera.[L39170] |
| Pharmacodynamics | Ropeginterferon alfa-2b acts through the interferon-alpha/beta receptor to initiate downstream JAK/STAT signalling leading to its therapeutic effects. Like other interferon alfa products, ropeginterferon alfa-2b may cause various toxicities, including endocrine, cardiovascular, pulmonary, ophthalmologic, dental/periodontal, renal, and dermatological toxicity. In addition, interferon alfa has been associated with hepatotoxicity, including increases in serum ALT, AST, GGT, and bilirubin; ropeginterferon alfa-2b is contraindicated in patients with moderate to severe (Child-Pugh B or C) hepatic impairment. Pancreatitis and colitis, including fatal ulcerative/hemorrhagic/ischemic colitis, have occurred in patients treated with interferon alfa. Significant toxicity of any kind may require treatment discontinuation. Interferon alfa treatment has decreased peripheral blood counts, including thrombocytopenia and leukopenia, and altered lipid levels, including hyperlipidemia, hypertriglyceridemia, and dyslipidemia. Hypersensitivity reactions, including anaphylaxis, may occur; ropeginterferon alfa-2b is contraindicated in hypersensitive patients and those with known hypersensitivity to other interferons. Life-threatening or fatal neuropsychiatric reactions may occur, including in patients without prior history; ropeginterferon alfa-2b is contraindicated in patients with a history of severe psychiatric disorders. Finally, ropeginterferon alfa-2b can cause fetal harm and should be used with caution in females of reproductive potential.[L39170] |
| Mechanism of Action | Polycythemia vera (PV) is the most common Philadelphia chromosome-negative myeloproliferative neoplasm (MPN), which also includes essential thrombocytopenia and myelofibrosis.[A242000, A242005] PV is characterized by increased hematocrit and platelet/leukocyte counts, an increased risk for hemorrhage and thromboembolic events, and a long-term propensity for myelofibrosis and leukemia. The main driver mutation, _JAK2_ V617F, is present in >95% of PV patients and results in constitutive JAK/STAT signalling; other exon 12 mutations in _JAK2_ may also result in PV. PV results in clonal hematopoietic stem cells, such that they form endogenous erythroid colonies (EECs) _in vitro_.[A242000] Interferon alfa-2b has been used for decades in PV despite the lack of formal approval.[A242005] Although the mechanism of action is unclear, interferon alfa-2b is known to bind the interferon-alpha/beta receptor (IFNAR) and activate downstream JAK/STAT signalling.[A242005, L39170] The overall result is a series of anti-proliferative, anti-angiogenic, pro-apoptotic, and immunomodulatory effects, including augmenting T-cell, macrophage, and natural killer cells.[A242005] Interestingly, _in vitro_ studies have revealed that ropeginterferon alfa-2b is specific to some extent for _JAK2_-mutant EECs, a result that is in line with the reduced allelic burden observed in clinical trials.[A242010, A242015] Partial and complete molecular and hematological responses have been achieved with ropeginterferon alfa-2b.[A242015] |
| Toxicity | Ropeginterferon alfa-2b overdose may present with influenza-like symptoms or other adverse reactions. As there is no known antidote, symptomatic and supportive care should be administered in the result of an overdose. Ropeginterferon alfa-2b is not mutagenic in standard assays but has not been tested for carcinogenic potential.[L39170] |
| Metabolism | Ropeginterferon alfa-2b is expected to be catabolized by various proteolytic enzymes.[L15811] |
| Absorption | In patients with polycythemia vera on a two-week dosing interval, the estimated steady-state Cmin was 1.4-12 ng/mL, Cmax was 4.4-31 ng/mL, and AUC was 1011-7809 ng |
| Ropeginterferon alfa-2b has an estimated geometric mean apparent volume of distribution (%CV) of 4.8 L (21%) in polycythemia vera patients.[L39170] | |
| Clearance | Ropeginterferon alfa-2b administered to polycythemia vera patients over a dose range of 100-500 µg has a clearance of 1.7-2.5 L/h.[L39170] |
| Categories | Cytochrome P-450 Enzyme Inhibitors |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Interferon alpha/beta receptor (IFNAR) |
| Brand Name | NA |
| Company | NA |
| Brand Description | NA |
| Prescribed For | NA |
| Chemical Name | NA |
| Formulation | NA |
| Physical Appearance | NA |
| Route of Administration | NA |
| Recommended Dosage | NA |
| Contraindication | (2S)-1-[3,7-bis(2-methoxyethoxycarbonylamino)heptyl]pyrrolidine-2-carboxylic acid |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | NA |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 15765 |
| Therapeutic ID | Th1624 |
| Protein Name | Ropeginterferon alfa-2b |
| Sequence | >Th1624_Ropeginterferon_alfa-2b PCDLPQTHSLGSRRTLMLLAQMRRISLFSCLKDRHDFGFPQEEFGNQFQKAETIPVLHEMIQQIFNLFSTKDSSAAWDETLLDKFYTELYQQLNDLEACVIQGVGVTETPLMKEDSILAVRKYFQRITLYLKEKKYSPCAWEVVRAEIMRSFSLSTNLQESLRSKE |
| Molecular Weight | 60000 |
| Chemical Formula | C16H29N3O6(C2H4O)n(C2H4O)n |
| Isoelectric Point | NA |
| Hydrophobicity | NA |
| Melting point | NA |
| Half-life | Ropeginterferon alfa-2b administered to polycythemia vera patients over a dose range of 100-500 µg has a half-life of approximately seven days.[L39170] |
| Description | Polycythemia vera (PV) is the most common Philadelphia chromosome-negative myeloproliferative neoplasm (MPN), characterized by increased hematocrit and platelet/leukocyte counts, an increased risk for hemorrhage and thromboembolic events, and a long-term propensity for myelofibrosis and leukemia.[A242000, A242005] [Interferon alfa-2b] has been used for decades to treat PV but requires frequent dosing and is not tolerated by all patients.[A242005] Ropeginterferon alfa-2b is a next-generation mono-pegylated type I interferon produced from proline-IFN-a-2b in _Escherichia coli_ that has high tolerability and a long half-life.[A242015, L39170] Ropeginterferon alfa-2b has shown efficacy in PV in _in vitro_ and _in vivo_ models and clinical trials.[A242010, A242015] Ropeginterferon alfa-2b was approved by the FDA on November 12, 2021, and is currently marketed under the trademark BESREMi by PharmaEssentia Corporation.[L39170] |
| Indication/Disease | Ropeginterferon alfa-2b is indicated for the treatment of adult patients with polycythemia vera.[L39170] |
| Pharmacodynamics | Ropeginterferon alfa-2b acts through the interferon-alpha/beta receptor to initiate downstream JAK/STAT signalling leading to its therapeutic effects. Like other interferon alfa products, ropeginterferon alfa-2b may cause various toxicities, including endocrine, cardiovascular, pulmonary, ophthalmologic, dental/periodontal, renal, and dermatological toxicity. In addition, interferon alfa has been associated with hepatotoxicity, including increases in serum ALT, AST, GGT, and bilirubin; ropeginterferon alfa-2b is contraindicated in patients with moderate to severe (Child-Pugh B or C) hepatic impairment. Pancreatitis and colitis, including fatal ulcerative/hemorrhagic/ischemic colitis, have occurred in patients treated with interferon alfa. Significant toxicity of any kind may require treatment discontinuation. Interferon alfa treatment has decreased peripheral blood counts, including thrombocytopenia and leukopenia, and altered lipid levels, including hyperlipidemia, hypertriglyceridemia, and dyslipidemia. Hypersensitivity reactions, including anaphylaxis, may occur; ropeginterferon alfa-2b is contraindicated in hypersensitive patients and those with known hypersensitivity to other interferons. Life-threatening or fatal neuropsychiatric reactions may occur, including in patients without prior history; ropeginterferon alfa-2b is contraindicated in patients with a history of severe psychiatric disorders. Finally, ropeginterferon alfa-2b can cause fetal harm and should be used with caution in females of reproductive potential.[L39170] |
| Mechanism of Action | Polycythemia vera (PV) is the most common Philadelphia chromosome-negative myeloproliferative neoplasm (MPN), which also includes essential thrombocytopenia and myelofibrosis.[A242000, A242005] PV is characterized by increased hematocrit and platelet/leukocyte counts, an increased risk for hemorrhage and thromboembolic events, and a long-term propensity for myelofibrosis and leukemia. The main driver mutation, _JAK2_ V617F, is present in >95% of PV patients and results in constitutive JAK/STAT signalling; other exon 12 mutations in _JAK2_ may also result in PV. PV results in clonal hematopoietic stem cells, such that they form endogenous erythroid colonies (EECs) _in vitro_.[A242000] Interferon alfa-2b has been used for decades in PV despite the lack of formal approval.[A242005] Although the mechanism of action is unclear, interferon alfa-2b is known to bind the interferon-alpha/beta receptor (IFNAR) and activate downstream JAK/STAT signalling.[A242005, L39170] The overall result is a series of anti-proliferative, anti-angiogenic, pro-apoptotic, and immunomodulatory effects, including augmenting T-cell, macrophage, and natural killer cells.[A242005] Interestingly, _in vitro_ studies have revealed that ropeginterferon alfa-2b is specific to some extent for _JAK2_-mutant EECs, a result that is in line with the reduced allelic burden observed in clinical trials.[A242010, A242015] Partial and complete molecular and hematological responses have been achieved with ropeginterferon alfa-2b.[A242015] |
| Toxicity | Ropeginterferon alfa-2b overdose may present with influenza-like symptoms or other adverse reactions. As there is no known antidote, symptomatic and supportive care should be administered in the result of an overdose. Ropeginterferon alfa-2b is not mutagenic in standard assays but has not been tested for carcinogenic potential.[L39170] |
| Metabolism | Ropeginterferon alfa-2b is expected to be catabolized by various proteolytic enzymes.[L15811] |
| Absorption | In patients with polycythemia vera on a two-week dosing interval, the estimated steady-state Cmin was 1.4-12 ng/mL, Cmax was 4.4-31 ng/mL, and AUC was 1011-7809 ng |
| Ropeginterferon alfa-2b has an estimated geometric mean apparent volume of distribution (%CV) of 4.8 L (21%) in polycythemia vera patients.[L39170] | |
| Clearance | Ropeginterferon alfa-2b administered to polycythemia vera patients over a dose range of 100-500 µg has a clearance of 1.7-2.5 L/h.[L39170] |
| Categories | Immunosuppressive Agents |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Interferon alpha/beta receptor (IFNAR) |
| Brand Name | NA |
| Company | NA |
| Brand Description | NA |
| Prescribed For | NA |
| Chemical Name | NA |
| Formulation | NA |
| Physical Appearance | NA |
| Route of Administration | NA |
| Recommended Dosage | NA |
| Contraindication | (2S)-1-[3,7-bis(2-methoxyethoxycarbonylamino)heptyl]pyrrolidine-2-carboxylic acid |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | NA |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 15766 |
| Therapeutic ID | Th1624 |
| Protein Name | Ropeginterferon alfa-2b |
| Sequence | >Th1624_Ropeginterferon_alfa-2b PCDLPQTHSLGSRRTLMLLAQMRRISLFSCLKDRHDFGFPQEEFGNQFQKAETIPVLHEMIQQIFNLFSTKDSSAAWDETLLDKFYTELYQQLNDLEACVIQGVGVTETPLMKEDSILAVRKYFQRITLYLKEKKYSPCAWEVVRAEIMRSFSLSTNLQESLRSKE |
| Molecular Weight | 60000 |
| Chemical Formula | C16H29N3O6(C2H4O)n(C2H4O)n |
| Isoelectric Point | NA |
| Hydrophobicity | NA |
| Melting point | NA |
| Half-life | Ropeginterferon alfa-2b administered to polycythemia vera patients over a dose range of 100-500 µg has a half-life of approximately seven days.[L39170] |
| Description | Polycythemia vera (PV) is the most common Philadelphia chromosome-negative myeloproliferative neoplasm (MPN), characterized by increased hematocrit and platelet/leukocyte counts, an increased risk for hemorrhage and thromboembolic events, and a long-term propensity for myelofibrosis and leukemia.[A242000, A242005] [Interferon alfa-2b] has been used for decades to treat PV but requires frequent dosing and is not tolerated by all patients.[A242005] Ropeginterferon alfa-2b is a next-generation mono-pegylated type I interferon produced from proline-IFN-a-2b in _Escherichia coli_ that has high tolerability and a long half-life.[A242015, L39170] Ropeginterferon alfa-2b has shown efficacy in PV in _in vitro_ and _in vivo_ models and clinical trials.[A242010, A242015] Ropeginterferon alfa-2b was approved by the FDA on November 12, 2021, and is currently marketed under the trademark BESREMi by PharmaEssentia Corporation.[L39170] |
| Indication/Disease | Ropeginterferon alfa-2b is indicated for the treatment of adult patients with polycythemia vera.[L39170] |
| Pharmacodynamics | Ropeginterferon alfa-2b acts through the interferon-alpha/beta receptor to initiate downstream JAK/STAT signalling leading to its therapeutic effects. Like other interferon alfa products, ropeginterferon alfa-2b may cause various toxicities, including endocrine, cardiovascular, pulmonary, ophthalmologic, dental/periodontal, renal, and dermatological toxicity. In addition, interferon alfa has been associated with hepatotoxicity, including increases in serum ALT, AST, GGT, and bilirubin; ropeginterferon alfa-2b is contraindicated in patients with moderate to severe (Child-Pugh B or C) hepatic impairment. Pancreatitis and colitis, including fatal ulcerative/hemorrhagic/ischemic colitis, have occurred in patients treated with interferon alfa. Significant toxicity of any kind may require treatment discontinuation. Interferon alfa treatment has decreased peripheral blood counts, including thrombocytopenia and leukopenia, and altered lipid levels, including hyperlipidemia, hypertriglyceridemia, and dyslipidemia. Hypersensitivity reactions, including anaphylaxis, may occur; ropeginterferon alfa-2b is contraindicated in hypersensitive patients and those with known hypersensitivity to other interferons. Life-threatening or fatal neuropsychiatric reactions may occur, including in patients without prior history; ropeginterferon alfa-2b is contraindicated in patients with a history of severe psychiatric disorders. Finally, ropeginterferon alfa-2b can cause fetal harm and should be used with caution in females of reproductive potential.[L39170] |
| Mechanism of Action | Polycythemia vera (PV) is the most common Philadelphia chromosome-negative myeloproliferative neoplasm (MPN), which also includes essential thrombocytopenia and myelofibrosis.[A242000, A242005] PV is characterized by increased hematocrit and platelet/leukocyte counts, an increased risk for hemorrhage and thromboembolic events, and a long-term propensity for myelofibrosis and leukemia. The main driver mutation, _JAK2_ V617F, is present in >95% of PV patients and results in constitutive JAK/STAT signalling; other exon 12 mutations in _JAK2_ may also result in PV. PV results in clonal hematopoietic stem cells, such that they form endogenous erythroid colonies (EECs) _in vitro_.[A242000] Interferon alfa-2b has been used for decades in PV despite the lack of formal approval.[A242005] Although the mechanism of action is unclear, interferon alfa-2b is known to bind the interferon-alpha/beta receptor (IFNAR) and activate downstream JAK/STAT signalling.[A242005, L39170] The overall result is a series of anti-proliferative, anti-angiogenic, pro-apoptotic, and immunomodulatory effects, including augmenting T-cell, macrophage, and natural killer cells.[A242005] Interestingly, _in vitro_ studies have revealed that ropeginterferon alfa-2b is specific to some extent for _JAK2_-mutant EECs, a result that is in line with the reduced allelic burden observed in clinical trials.[A242010, A242015] Partial and complete molecular and hematological responses have been achieved with ropeginterferon alfa-2b.[A242015] |
| Toxicity | Ropeginterferon alfa-2b overdose may present with influenza-like symptoms or other adverse reactions. As there is no known antidote, symptomatic and supportive care should be administered in the result of an overdose. Ropeginterferon alfa-2b is not mutagenic in standard assays but has not been tested for carcinogenic potential.[L39170] |
| Metabolism | Ropeginterferon alfa-2b is expected to be catabolized by various proteolytic enzymes.[L15811] |
| Absorption | In patients with polycythemia vera on a two-week dosing interval, the estimated steady-state Cmin was 1.4-12 ng/mL, Cmax was 4.4-31 ng/mL, and AUC was 1011-7809 ng |
| Ropeginterferon alfa-2b has an estimated geometric mean apparent volume of distribution (%CV) of 4.8 L (21%) in polycythemia vera patients.[L39170] | |
| Clearance | Ropeginterferon alfa-2b administered to polycythemia vera patients over a dose range of 100-500 µg has a clearance of 1.7-2.5 L/h.[L39170] |
| Categories | Immunotherapy |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Interferon alpha/beta receptor (IFNAR) |
| Brand Name | NA |
| Company | NA |
| Brand Description | NA |
| Prescribed For | NA |
| Chemical Name | NA |
| Formulation | NA |
| Physical Appearance | NA |
| Route of Administration | NA |
| Recommended Dosage | NA |
| Contraindication | (2S)-1-[3,7-bis(2-methoxyethoxycarbonylamino)heptyl]pyrrolidine-2-carboxylic acid |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | NA |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 15767 |
| Therapeutic ID | Th1624 |
| Protein Name | Ropeginterferon alfa-2b |
| Sequence | >Th1624_Ropeginterferon_alfa-2b PCDLPQTHSLGSRRTLMLLAQMRRISLFSCLKDRHDFGFPQEEFGNQFQKAETIPVLHEMIQQIFNLFSTKDSSAAWDETLLDKFYTELYQQLNDLEACVIQGVGVTETPLMKEDSILAVRKYFQRITLYLKEKKYSPCAWEVVRAEIMRSFSLSTNLQESLRSKE |
| Molecular Weight | 60000 |
| Chemical Formula | C16H29N3O6(C2H4O)n(C2H4O)n |
| Isoelectric Point | NA |
| Hydrophobicity | NA |
| Melting point | NA |
| Half-life | Ropeginterferon alfa-2b administered to polycythemia vera patients over a dose range of 100-500 µg has a half-life of approximately seven days.[L39170] |
| Description | Polycythemia vera (PV) is the most common Philadelphia chromosome-negative myeloproliferative neoplasm (MPN), characterized by increased hematocrit and platelet/leukocyte counts, an increased risk for hemorrhage and thromboembolic events, and a long-term propensity for myelofibrosis and leukemia.[A242000, A242005] [Interferon alfa-2b] has been used for decades to treat PV but requires frequent dosing and is not tolerated by all patients.[A242005] Ropeginterferon alfa-2b is a next-generation mono-pegylated type I interferon produced from proline-IFN-a-2b in _Escherichia coli_ that has high tolerability and a long half-life.[A242015, L39170] Ropeginterferon alfa-2b has shown efficacy in PV in _in vitro_ and _in vivo_ models and clinical trials.[A242010, A242015] Ropeginterferon alfa-2b was approved by the FDA on November 12, 2021, and is currently marketed under the trademark BESREMi by PharmaEssentia Corporation.[L39170] |
| Indication/Disease | Ropeginterferon alfa-2b is indicated for the treatment of adult patients with polycythemia vera.[L39170] |
| Pharmacodynamics | Ropeginterferon alfa-2b acts through the interferon-alpha/beta receptor to initiate downstream JAK/STAT signalling leading to its therapeutic effects. Like other interferon alfa products, ropeginterferon alfa-2b may cause various toxicities, including endocrine, cardiovascular, pulmonary, ophthalmologic, dental/periodontal, renal, and dermatological toxicity. In addition, interferon alfa has been associated with hepatotoxicity, including increases in serum ALT, AST, GGT, and bilirubin; ropeginterferon alfa-2b is contraindicated in patients with moderate to severe (Child-Pugh B or C) hepatic impairment. Pancreatitis and colitis, including fatal ulcerative/hemorrhagic/ischemic colitis, have occurred in patients treated with interferon alfa. Significant toxicity of any kind may require treatment discontinuation. Interferon alfa treatment has decreased peripheral blood counts, including thrombocytopenia and leukopenia, and altered lipid levels, including hyperlipidemia, hypertriglyceridemia, and dyslipidemia. Hypersensitivity reactions, including anaphylaxis, may occur; ropeginterferon alfa-2b is contraindicated in hypersensitive patients and those with known hypersensitivity to other interferons. Life-threatening or fatal neuropsychiatric reactions may occur, including in patients without prior history; ropeginterferon alfa-2b is contraindicated in patients with a history of severe psychiatric disorders. Finally, ropeginterferon alfa-2b can cause fetal harm and should be used with caution in females of reproductive potential.[L39170] |
| Mechanism of Action | Polycythemia vera (PV) is the most common Philadelphia chromosome-negative myeloproliferative neoplasm (MPN), which also includes essential thrombocytopenia and myelofibrosis.[A242000, A242005] PV is characterized by increased hematocrit and platelet/leukocyte counts, an increased risk for hemorrhage and thromboembolic events, and a long-term propensity for myelofibrosis and leukemia. The main driver mutation, _JAK2_ V617F, is present in >95% of PV patients and results in constitutive JAK/STAT signalling; other exon 12 mutations in _JAK2_ may also result in PV. PV results in clonal hematopoietic stem cells, such that they form endogenous erythroid colonies (EECs) _in vitro_.[A242000] Interferon alfa-2b has been used for decades in PV despite the lack of formal approval.[A242005] Although the mechanism of action is unclear, interferon alfa-2b is known to bind the interferon-alpha/beta receptor (IFNAR) and activate downstream JAK/STAT signalling.[A242005, L39170] The overall result is a series of anti-proliferative, anti-angiogenic, pro-apoptotic, and immunomodulatory effects, including augmenting T-cell, macrophage, and natural killer cells.[A242005] Interestingly, _in vitro_ studies have revealed that ropeginterferon alfa-2b is specific to some extent for _JAK2_-mutant EECs, a result that is in line with the reduced allelic burden observed in clinical trials.[A242010, A242015] Partial and complete molecular and hematological responses have been achieved with ropeginterferon alfa-2b.[A242015] |
| Toxicity | Ropeginterferon alfa-2b overdose may present with influenza-like symptoms or other adverse reactions. As there is no known antidote, symptomatic and supportive care should be administered in the result of an overdose. Ropeginterferon alfa-2b is not mutagenic in standard assays but has not been tested for carcinogenic potential.[L39170] |
| Metabolism | Ropeginterferon alfa-2b is expected to be catabolized by various proteolytic enzymes.[L15811] |
| Absorption | In patients with polycythemia vera on a two-week dosing interval, the estimated steady-state Cmin was 1.4-12 ng/mL, Cmax was 4.4-31 ng/mL, and AUC was 1011-7809 ng |
| Ropeginterferon alfa-2b has an estimated geometric mean apparent volume of distribution (%CV) of 4.8 L (21%) in polycythemia vera patients.[L39170] | |
| Clearance | Ropeginterferon alfa-2b administered to polycythemia vera patients over a dose range of 100-500 µg has a clearance of 1.7-2.5 L/h.[L39170] |
| Categories | Interferons |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Interferon alpha/beta receptor (IFNAR) |
| Brand Name | NA |
| Company | NA |
| Brand Description | NA |
| Prescribed For | NA |
| Chemical Name | NA |
| Formulation | NA |
| Physical Appearance | NA |
| Route of Administration | NA |
| Recommended Dosage | NA |
| Contraindication | (2S)-1-[3,7-bis(2-methoxyethoxycarbonylamino)heptyl]pyrrolidine-2-carboxylic acid |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | NA |
| Remarks | NA |
| Primary information | |
|---|---|
| ID | 15768 |
| Therapeutic ID | Th1624 |
| Protein Name | Ropeginterferon alfa-2b |
| Sequence | >Th1624_Ropeginterferon_alfa-2b PCDLPQTHSLGSRRTLMLLAQMRRISLFSCLKDRHDFGFPQEEFGNQFQKAETIPVLHEMIQQIFNLFSTKDSSAAWDETLLDKFYTELYQQLNDLEACVIQGVGVTETPLMKEDSILAVRKYFQRITLYLKEKKYSPCAWEVVRAEIMRSFSLSTNLQESLRSKE |
| Molecular Weight | 60000 |
| Chemical Formula | C16H29N3O6(C2H4O)n(C2H4O)n |
| Isoelectric Point | NA |
| Hydrophobicity | NA |
| Melting point | NA |
| Half-life | Ropeginterferon alfa-2b administered to polycythemia vera patients over a dose range of 100-500 µg has a half-life of approximately seven days.[L39170] |
| Description | Polycythemia vera (PV) is the most common Philadelphia chromosome-negative myeloproliferative neoplasm (MPN), characterized by increased hematocrit and platelet/leukocyte counts, an increased risk for hemorrhage and thromboembolic events, and a long-term propensity for myelofibrosis and leukemia.[A242000, A242005] [Interferon alfa-2b] has been used for decades to treat PV but requires frequent dosing and is not tolerated by all patients.[A242005] Ropeginterferon alfa-2b is a next-generation mono-pegylated type I interferon produced from proline-IFN-a-2b in _Escherichia coli_ that has high tolerability and a long half-life.[A242015, L39170] Ropeginterferon alfa-2b has shown efficacy in PV in _in vitro_ and _in vivo_ models and clinical trials.[A242010, A242015] Ropeginterferon alfa-2b was approved by the FDA on November 12, 2021, and is currently marketed under the trademark BESREMi by PharmaEssentia Corporation.[L39170] |
| Indication/Disease | Ropeginterferon alfa-2b is indicated for the treatment of adult patients with polycythemia vera.[L39170] |
| Pharmacodynamics | Ropeginterferon alfa-2b acts through the interferon-alpha/beta receptor to initiate downstream JAK/STAT signalling leading to its therapeutic effects. Like other interferon alfa products, ropeginterferon alfa-2b may cause various toxicities, including endocrine, cardiovascular, pulmonary, ophthalmologic, dental/periodontal, renal, and dermatological toxicity. In addition, interferon alfa has been associated with hepatotoxicity, including increases in serum ALT, AST, GGT, and bilirubin; ropeginterferon alfa-2b is contraindicated in patients with moderate to severe (Child-Pugh B or C) hepatic impairment. Pancreatitis and colitis, including fatal ulcerative/hemorrhagic/ischemic colitis, have occurred in patients treated with interferon alfa. Significant toxicity of any kind may require treatment discontinuation. Interferon alfa treatment has decreased peripheral blood counts, including thrombocytopenia and leukopenia, and altered lipid levels, including hyperlipidemia, hypertriglyceridemia, and dyslipidemia. Hypersensitivity reactions, including anaphylaxis, may occur; ropeginterferon alfa-2b is contraindicated in hypersensitive patients and those with known hypersensitivity to other interferons. Life-threatening or fatal neuropsychiatric reactions may occur, including in patients without prior history; ropeginterferon alfa-2b is contraindicated in patients with a history of severe psychiatric disorders. Finally, ropeginterferon alfa-2b can cause fetal harm and should be used with caution in females of reproductive potential.[L39170] |
| Mechanism of Action | Polycythemia vera (PV) is the most common Philadelphia chromosome-negative myeloproliferative neoplasm (MPN), which also includes essential thrombocytopenia and myelofibrosis.[A242000, A242005] PV is characterized by increased hematocrit and platelet/leukocyte counts, an increased risk for hemorrhage and thromboembolic events, and a long-term propensity for myelofibrosis and leukemia. The main driver mutation, _JAK2_ V617F, is present in >95% of PV patients and results in constitutive JAK/STAT signalling; other exon 12 mutations in _JAK2_ may also result in PV. PV results in clonal hematopoietic stem cells, such that they form endogenous erythroid colonies (EECs) _in vitro_.[A242000] Interferon alfa-2b has been used for decades in PV despite the lack of formal approval.[A242005] Although the mechanism of action is unclear, interferon alfa-2b is known to bind the interferon-alpha/beta receptor (IFNAR) and activate downstream JAK/STAT signalling.[A242005, L39170] The overall result is a series of anti-proliferative, anti-angiogenic, pro-apoptotic, and immunomodulatory effects, including augmenting T-cell, macrophage, and natural killer cells.[A242005] Interestingly, _in vitro_ studies have revealed that ropeginterferon alfa-2b is specific to some extent for _JAK2_-mutant EECs, a result that is in line with the reduced allelic burden observed in clinical trials.[A242010, A242015] Partial and complete molecular and hematological responses have been achieved with ropeginterferon alfa-2b.[A242015] |
| Toxicity | Ropeginterferon alfa-2b overdose may present with influenza-like symptoms or other adverse reactions. As there is no known antidote, symptomatic and supportive care should be administered in the result of an overdose. Ropeginterferon alfa-2b is not mutagenic in standard assays but has not been tested for carcinogenic potential.[L39170] |
| Metabolism | Ropeginterferon alfa-2b is expected to be catabolized by various proteolytic enzymes.[L15811] |
| Absorption | In patients with polycythemia vera on a two-week dosing interval, the estimated steady-state Cmin was 1.4-12 ng/mL, Cmax was 4.4-31 ng/mL, and AUC was 1011-7809 ng |
| Ropeginterferon alfa-2b has an estimated geometric mean apparent volume of distribution (%CV) of 4.8 L (21%) in polycythemia vera patients.[L39170] | |
| Clearance | Ropeginterferon alfa-2b administered to polycythemia vera patients over a dose range of 100-500 µg has a clearance of 1.7-2.5 L/h.[L39170] |
| Categories | Myelosuppressive Agents |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Interferon alpha/beta receptor (IFNAR) |
| Brand Name | NA |
| Company | NA |
| Brand Description | NA |
| Prescribed For | NA |
| Chemical Name | NA |
| Formulation | NA |
| Physical Appearance | NA |
| Route of Administration | NA |
| Recommended Dosage | NA |
| Contraindication | (2S)-1-[3,7-bis(2-methoxyethoxycarbonylamino)heptyl]pyrrolidine-2-carboxylic acid |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | NA |
| Remarks | NA |