Ropeginterferon alfa-2b API Manufacturers

General Description:

Ropeginterferon alfa-2b, identified by CAS number 1335098-50-4, is a notable compound with significant therapeutic applications. 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.

Indications:

This drug is primarily indicated for: Ropeginterferon alfa-2b is indicated for the treatment of adult patients with polycythemia vera. Its use in specific medical scenarios underscores its importance in the therapeutic landscape.

Metabolism:

Ropeginterferon alfa-2b undergoes metabolic processing primarily in: Ropeginterferon alfa-2b is expected to be catabolized by various proteolytic enzymes. This metabolic pathway ensures efficient processing of the drug, helping to minimize potential toxicity and side effects.

Absorption:

The absorption characteristics of Ropeginterferon alfa-2b are crucial for its therapeutic efficacy: In patients with polycythemia vera on a two-week dosing interval, the estimated steady-state C_min was 1.4-12 ng/mL, C_max was 4.4-31 ng/mL, and AUC was 1011-7809 ng\*h/mL. The estimated geometric mean (%CV) of the absorption rate constant if 0.12 day^-1 (27%) and the estimated steady-state C_max occurs between 2-5 days. The drug's ability to rapidly penetrate into cells ensures quick onset of action.

Half-life:

The half-life of Ropeginterferon alfa-2b is an important consideration for its dosing schedule: Ropeginterferon alfa-2b administered to polycythemia vera patients over a dose range of 100-500 μg has a half-life of approximately seven days. This determines the duration of action and helps in formulating effective dosing regimens.

Route of Elimination:

The elimination of Ropeginterferon alfa-2b from the body primarily occurs through: Ropeginterferon alfa-2b is expected to be eliminated predominantly by hepatic metabolism. Understanding this pathway is essential for assessing potential drug accumulation and toxicity risks.

Volume of Distribution:

Ropeginterferon alfa-2b is distributed throughout the body with a volume of distribution of: Ropeginterferon alfa-2b has an estimated geometric mean apparent volume of distribution (%CV) of 4.8 L (21%) in polycythemia vera patients. This metric indicates how extensively the drug permeates into body tissues.

Clearance:

The clearance rate of Ropeginterferon alfa-2b is a critical factor in determining its safe and effective dosage: 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. It reflects the efficiency with which the drug is removed from the systemic circulation.

Pharmacodynamics:

Ropeginterferon alfa-2b exerts its therapeutic effects through: 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. The drug's ability to modulate various physiological processes underscores its efficacy in treating specific conditions.

Mechanism of Action:

Ropeginterferon alfa-2b functions by: 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. This mechanism highlights the drug's role in inhibiting or promoting specific biological pathways, contributing to its therapeutic effects.

Toxicity:

Classification:

Ropeginterferon alfa-2b belongs to the None, classified under the direct parent group Peptides. This compound is a part of the Organic Compounds, falling under the Organic Acids superclass, and categorized within the Carboxylic Acids and Derivatives class, specifically within the Amino Acids, Peptides, and Analogues subclass.

Categories:

Ropeginterferon alfa-2b is categorized under the following therapeutic classes: Adjuvants, Immunologic, Alfa Interferons, Antineoplastic and Immunomodulating Agents, Cancer immunotherapy, Cytochrome P-450 CYP1A2 Inhibitors, Cytochrome P-450 CYP1A2 Inhibitors (strength unknown), Cytochrome P-450 CYP2A6 Inhibitors, Cytochrome P-450 CYP2A6 Inhibitors (strength unknown), Cytochrome P-450 CYP2D6 Inhibitors, Cytochrome P-450 CYP2D6 Inhibitors (strength unknown), Cytochrome P-450 Enzyme Inhibitors, Immunosuppressive Agents, Immunotherapy, Interferons, Myelosuppressive Agents. These classifications highlight the drug's diverse therapeutic applications and its importance in treating various conditions.

Experimental Properties:

Further physical and chemical characteristics of Ropeginterferon alfa-2b include:

• Molecular Weight: 60000.0
• Molecular Formula: C16H29N3O6(C2H4O)n(C2H4O)n