Ropeginterferon alfa-2b

Identification

Summary

Ropeginterferon alfa-2b is a mono-pegylated type I interferon used to treat polycythemia vera.

Brand Names

Besremi

Generic Name

Ropeginterferon alfa-2b

DrugBank Accession Number

DB15119

Background

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.^1,2 Interferon alfa-2b has been used for decades to treat PV but requires frequent dosing and is not tolerated by all patients.² 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.^4,6 Ropeginterferon alfa-2b has shown efficacy in PV in in vitro and in vivo models and clinical trials.^3,4

Ropeginterferon alfa-2b was approved by the FDA on November 12, 2021, and is currently marketed under the trademark BESREMi by PharmaEssentia Corporation.⁶

Type

Biotech

Groups

Approved, Investigational

Biologic Classification

Protein Based Therapies
Interferons

Protein Structure

Protein Chemical Formula

C₁₆H₂₉N₃O₆(C₂H₄O)n(C₂H₄O)n

Protein Average Weight

60000.0 Da (approximate)

Sequences

Not Available

Synonyms

• Pegylated proline interferon alpha-2b
• Pegylated proline-interferon alpha-2b
• Ropeginterferon alfa-2b
• Ropeginterferon alfa-2b-njft

External IDs

• AOP2014
• P-1101
• P1101

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Pharmacology

Indication

Ropeginterferon alfa-2b is indicated for the treatment of adult patients with polycythemia vera.⁶

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Associated Conditions

Indication Type	Indication	Combined Product Details	Approval Level	Age Group	Patient Characteristics	Dose Form
Treatment of	Polycythemia vera (pv)		••••••••••••	•••••		•••••••••• ••••••••
Treatment of	Polycythemia vera (pv)		••••••••••••	•••••		•••••••••

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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.⁶

Mechanism of action

Polycythemia vera (PV) is the most common Philadelphia chromosome-negative myeloproliferative neoplasm (MPN), which also includes essential thrombocytopenia and myelofibrosis.^1,2 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.¹

Interferon alfa-2b has been used for decades in PV despite the lack of formal approval.² 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.^2,6 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.² 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.^3,4 Partial and complete molecular and hematological responses have been achieved with ropeginterferon alfa-2b.⁴

Target	Actions	Organism
AInterferon alpha/beta receptor (IFNAR)	binder	Humans

Absorption

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.⁶

Volume of distribution

Ropeginterferon alfa-2b has an estimated geometric mean apparent volume of distribution (%CV) of 4.8 L (21%) in polycythemia vera patients.⁶

Protein binding

Not Available

Metabolism

Ropeginterferon alfa-2b is expected to be catabolized by various proteolytic enzymes.⁵

Route of elimination

Ropeginterferon alfa-2b is expected to be eliminated predominantly by hepatic metabolism.⁵

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.⁶

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.⁶

Adverse Effects

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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.⁶

Pathways

Not Available

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Not Available

Interactions

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This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.

• Approved
• Vet approved
• Nutraceutical
• Illicit
• Withdrawn
• Investigational
• Experimental
• All Drugs

Drug	Interaction
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1,2-Benzodiazepine	The risk or severity of neuropsychiatric effects can be increased when Ropeginterferon alfa-2b is combined with 1,2-Benzodiazepine.
Abatacept	The risk or severity of adverse effects can be increased when Abatacept is combined with Ropeginterferon alfa-2b.
Abciximab	The risk or severity of bleeding can be increased when Abciximab is combined with Ropeginterferon alfa-2b.
Acebutolol	The metabolism of Acebutolol can be decreased when combined with Ropeginterferon alfa-2b.
Acenocoumarol	The metabolism of Acenocoumarol can be decreased when combined with Ropeginterferon alfa-2b.

Food Interactions

No interactions found.

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Brand Name Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End	Region	Image
Besremi	Injection, solution	250 ?g/0.5ml	Subcutaneous	Aop Orphan Pharmaceuticals Gmb H	2020-12-16	Not applicable
Besremi	Injection, solution	250 ?g/0.5ml	Subcutaneous	Aop Orphan Pharmaceuticals Gmb H	2021-03-03	Not applicable
BESREMi	Injection	500 ug/1mL	Subcutaneous	PharmaEssentia USA	2021-11-12	Not applicable
Besremi	Injection, solution	500 ?g/0.5ml	Subcutaneous	Aop Orphan Pharmaceuticals Gmb H	2020-12-16	Not applicable

Categories

ATC Codes

L03AB15 — Ropeginterferon alfa-2b

• L03AB — Interferons
• L03A — IMMUNOSTIMULANTS
• L03 — IMMUNOSTIMULANTS
• L — ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS

Drug Categories

• 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

Chemical TaxonomyProvided by Classyfire

Description

Not Available

Kingdom

Organic Compounds

Super Class

Organic Acids

Class

Carboxylic Acids and Derivatives

Sub Class

Amino Acids, Peptides, and Analogues

Direct Parent

Peptides

Alternative Parents

Not Available

Substituents

Not Available

Molecular Framework

Not Available

External Descriptors

Not Available

Affected organisms

• Humans and other mammals

Chemical Identifiers

UNII

981TME683S

CAS number

1335098-50-4

References

General References

1. Bartalucci N, Guglielmelli P, Vannucchi AM: Polycythemia vera: the current status of preclinical models and therapeutic targets. Expert Opin Ther Targets. 2020 Jul;24(7):615-628. doi: 10.1080/14728222.2020.1762176. Epub 2020 May 18. [Article]
2. How J, Hobbs G: Use of Interferon Alfa in the Treatment of Myeloproliferative Neoplasms: Perspectives and Review of the Literature. Cancers (Basel). 2020 Jul 18;12(7). pii: cancers12071954. doi: 10.3390/cancers12071954. [Article]
3. Verger E, Soret-Dulphy J, Maslah N, Roy L, Rey J, Ghrieb Z, Kralovics R, Gisslinger H, Grohmann-Izay B, Klade C, Chomienne C, Giraudier S, Cassinat B, Kiladjian JJ: Ropeginterferon alpha-2b targets JAK2V617F-positive polycythemia vera cells in vitro and in vivo. Blood Cancer J. 2018 Oct 4;8(10):94. doi: 10.1038/s41408-018-0133-0. [Article]
4. Gisslinger H, Zagrijtschuk O, Buxhofer-Ausch V, Thaler J, Schloegl E, Gastl GA, Wolf D, Kralovics R, Gisslinger B, Strecker K, Egle A, Melchardt T, Burgstaller S, Willenbacher E, Schalling M, Them NC, Kadlecova P, Klade C, Greil R: Ropeginterferon alfa-2b, a novel IFNalpha-2b, induces high response rates with low toxicity in patients with polycythemia vera. Blood. 2015 Oct 8;126(15):1762-9. doi: 10.1182/blood-2015-04-637280. Epub 2015 Aug 10. [Article]
5. EMA Approved Products: Besremi (ropeginterferon alfa-2b ) solution for injection [Link]
6. FDA Approved Drug Products: BESREMi (ropeginterferon alfa-2b-njft) injection [Link]

External Links

RxNav

2587059

Wikipedia

Ropeginterferon_alfa-2b

Clinical Trials

Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">

Phase	Status	Purpose	Conditions	Count
3	Active Not Recruiting	Treatment	Coronavirus Disease 2019 (COVID‑19)	1
3	Active Not Recruiting	Treatment	Essential Thrombocythemia (ET)	1
3	Completed	Other	Polycythemia Vera (PV)	1
3	Completed	Prevention	Chronic Myeloid Leukemia in Remission	1
3	Completed	Treatment	Chronic Hepatitis C Virus (HCV) Infection	1

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Not Available

Dosage Forms

Form	Route	Strength
Injection	Subcutaneous	500 ug/1mL
Injection, solution	Subcutaneous	250 MCG/0.5ML
Injection, solution	Subcutaneous	250 ?g/0.5ml
Injection, solution	Subcutaneous	250 g/0.5ml
Injection, solution	Subcutaneous	500 MCG/0.5ML
Injection, solution	Subcutaneous	500 ?g/0.5ml

Prices

Not Available

Patents

Not Available

Properties

State

Solid

Experimental Properties

Not Available

Targets

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Details1. Interferon alpha/beta receptor (IFNAR) (Protein Group)

Kind

Protein group

Organism

Humans

Pharmacological action

Yes

Actions

Binder

Curator comments

Although the exact mechanism of action remains unclear, ropeginterferon alfa-2b binds the interferon alfa/beta receptor to induce downstream JAK-STAT signalling.

General Function

Type i interferon receptor activity

Specific Function

Associates with IFNAR2 to form the type I interferon receptor. Receptor for interferons alpha and beta. Binding to type I IFNs triggers tyrosine phosphorylation of a number of proteins including JA...

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Components:

Name	UniProt ID
Interferon alpha/beta receptor 1	P17181
Interferon alpha/beta receptor 2	P48551

References

1. FDA Approved Drug Products: BESREMi (ropeginterferon alfa-2b-njft) injection [Link]

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Drug created at May 20, 2019 14:51 / Updated at July 18, 2023 22:57