| Candidate ID: | R1556 |
| Source ID: | DB15119 |
| Source Type: | approved; investigational |
| Compound Type: |
biotech
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| Compound Name: |
Ropeginterferon alfa-2b
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| Synonyms: |
Ropeginterferon alfa-2b
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| Molecular Formula: |
--
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| SMILES: |
--
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| DrugBank 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. has been used for decades to treat PV but requires frequent dosing and is not tolerated by all patients. Ropeginterferon alfa-2b is a next-generation mono-pegylated type I interferon produced from proline-IFN-α-2b in _Escherichia coli_ that has high tolerability and a long half-life. Ropeginterferon alfa-2b has shown efficacy in PV in _in vitro_ and _in vivo_ models and clinical trials.
Ropeginterferon alfa-2b was approved by the FDA on November 12, 2021, and is currently marketed under the trademark BESREMi by PharmaEssentia Corporation.
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| CAS Number: |
1335098-50-4
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| Molecular Weight: |
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| DrugBank Indication: |
Ropeginterferon alfa-2b is indicated for the treatment of adult patients with polycythemia vera.
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| DrugBank Pharmacology: |
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.
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| DrugBank MoA: |
Polycythemia vera (PV) is the most common Philadelphia chromosome-negative myeloproliferative neoplasm (MPN), which also includes essential thrombocytopenia and myelofibrosis. 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_.
Interferon alfa-2b has been used for decades in PV despite the lack of formal approval. 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. 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. 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. Partial and complete molecular and hematological responses have been achieved with ropeginterferon alfa-2b.
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| Targets: |
Interferon alpha/beta receptor (IFNAR) binder
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| Inclusion Criteria: |
Therapeutic strategy associated
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