Identification

Name
Romiplostim
Accession Number
DB05332
Type
Biotech
Groups
Approved
Biologic Classification
Protein Based Therapies
Haematopoietic growth factors
Description

Romiplostim is a thrombopoiesis stimulating dimer Fc-peptide fusion protein (peptibody) to increase platelet production through activation of the thrombopoietin receptor. The peptibody molecule has two identical single-chain subunits, each one is made up of 269 amino acid residues. Each subunit consists of an IgG1 Fc carrier domain that is covalently attached to a polypeptide sequence that contains two binding domains to interact with thrombopoietin receptor c-Mpl. Each domain consists of 14 amino acids. Interestingly, romiplostim's amino acid sequence is not similar to that of endogenous thrombopoietin. Romiplostim is produced by recombinant DNA technology in Escherichia coli. FDA approved on August 22, 2008.

Protein chemical formula
C2634H4086N722O790S18
Protein average weight
59000.0 Da
Sequences
>Thrombopoietin receptor binding domain amino acid sequence 
IEGPTLRQWLAARA
>Amino acid sequence for Fc fusion compound
MDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYV
DGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKA
KGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLD
SDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGGIEGPTLR
QWLAARAGGGGGGGGIEGPTLRQWLAARA
Download FASTA Format
Synonyms
Not Available
External IDs
AMG 531 / AMG-531
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
NplatePowder, for solution250 mcgSubcutaneousAmgen2009-04-15Not applicableCanada
NplateInjection, powder, for solution500 μgSubcutaneousAmgen Europe B.V.2009-02-04Not applicableEu
NplateInjection, powder, for solution500 μgSubcutaneousAmgen Europe B.V.2009-02-04Not applicableEu
NplateInjection, powder, lyophilized, for solution500 ug/mLSubcutaneousAmgen2008-08-25Not applicableUs
NplateInjection, powder, for solution250 μgSubcutaneousAmgen Europe B.V.2009-02-04Not applicableEu
NplatePowder, for solution500 mcgSubcutaneousAmgen2009-04-15Not applicableCanada
NplateInjection, powder, for solution500 μgSubcutaneousAmgen Europe B.V.2009-02-04Not applicableEu
NplateInjection, powder, for solution250 μgSubcutaneousAmgen Europe B.V.2009-02-04Not applicableEu
NplateInjection, powder, for solution250 μgSubcutaneousAmgen Europe B.V.2009-02-04Not applicableEu
NplateInjection, powder, for solution250 μgSubcutaneousAmgen Europe B.V.2009-02-04Not applicableEu
Categories
UNII
GN5XU2DXKV
CAS number
267639-76-9

Pharmacology

Indication

Treatment of chronic immune thrombocytopenic purpura.

Structured Indications
Pharmacodynamics

Responses to platelet increase varies between patients thus indicating a need for individualization of dose. However, a dose dependent-increase in platelet counts have been observed in clinical trials. Does not affect platelet destruction.

Mechanism of action

Romiplostim is a thrombopoietin receptor agonist that activates intracellular transcriptional pathways via c-Mpl to increase production of platelets. It also works similarly to thrombopoietin (TPO), an endogenous glycoprotein hormone that regulates the production of platelets in the bone marrow.

TargetActionsOrganism
AThrombopoietin receptor
agonist
Human
Absorption

Cmax, healthy volunteers, subQ = 24-36 hours; Cmax, immune thrombocytopenia patients, subQ = 7-50 hours (median = 14 hours). Not affected by age, weight, or gender. Accumulation does not occur after six weekly doses of 3 mcg/kg romiplostim.

Volume of distribution

In healthy volunteers, non-linear decrease in Vd with increase IV dose of romiplostim which indicates saturation of c-Mpl receptors. Vd, 0.3 μg/kg = 122 mL/kg Vd, 10 μg/kg = 48.2 mL/kg

Protein binding
Not Available
Metabolism
Not Available
Route of elimination

Renal clearance (more dominant mode of clearance as dose increases) and
binding to c-Mpl receptors (dominant mode of clearance at low doses)

Half life

Immune thrombocytopenia patients, subQ = 3.5 days (median) (range 1-34 days)

Clearance
Not Available
Toxicity

The most common adverse reactions (≥ 5% higher patient incidence in Nplate versus placebo) are arthralgia, dizziness, insomnia, myalgia, pain in extremity, abdominal pain, shoulder pain, dyspepsia, and paresthesia. Headache was the most commonly reported adverse reaction that did not occur at ≥ 5% higher patient incidence in Nplate versus placebo. LD50 = 980 mg/kg.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
No interactions found.
Food Interactions
Not Available

References

General References
  1. Kumagai Y, Fujita T, Ozaki M, Sahashi K, Ohkura M, Ohtsu T, Arai Y, Sonehara Y, Nichol JL: Pharmacodynamics and pharmacokinetics of AMG 531, a thrombopoiesis-stimulating peptibody, in healthy Japanese subjects: a randomized, placebo-controlled study. J Clin Pharmacol. 2007 Dec;47(12):1489-97. Epub 2007 Oct 9. [PubMed:17925591]
  2. Rice L: Drug evaluation: AMG-531 for the treatment of thrombocytopenias. Curr Opin Investig Drugs. 2006 Sep;7(9):834-41. [PubMed:17002262]
  3. Keating GM: Romiplostim: a review of its use in immune thrombocytopenia. Drugs. 2012 Feb 12;72(3):415-35. doi: 10.2165/11208260-000000000-00000. [PubMed:22316355]
  4. Link [Link]
External Links
KEGG Drug
D08990
PubChem Substance
347910087
ChEMBL
CHEMBL1201832
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Romiplostim
ATC Codes
B02BX04 — Romiplostim
AHFS Codes
  • 20:16.00 — Hematopoietic Agents
FDA label
Download (232 KB)
MSDS
Download (479 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1RecruitingSupportive CareMalignancies, Hematologic1
1, 2Active Not RecruitingTreatmentPersistent Thrombocytopenia Following Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)1
1, 2CompletedPreventionCancer, Advanced / Tumors, Solid1
1, 2CompletedSupportive CareCancers / Chemotherapy-Induced Thrombocytopenia / Lymphoma, Hodgkins / Non-Hodgkin's Lymphoma (NHL) / Oncology / Thrombocytopenias1
1, 2CompletedTreatmentIdiopathic Thrombocytopenic Purpura (ITP) / Thrombocytopenia in Pediatric Subjects With Immune (Idiopathic) Thrombocytopenic Purpura (ITP) / Thrombocytopenia in Subjects With Immune (Idiopathic) Thrombocytopenic Purpura (ITP)1
1, 2CompletedTreatmentImmune Thrombocytopenia (ITP)1
1, 2CompletedTreatmentMalignant Lymphomas1
1, 2CompletedTreatmentThrombocytopenic Purpura1
2CompletedSupportive CareCancers / Chemotherapy-Induced Thrombocytopenia / Lung Cancer Non-Small Cell Cancer (NSCLC) / Lung Cancers / Neoplasms, Lung / Oncology / Thrombocytopenias / Tumors, Solid1
2CompletedSupportive CareMyelodysplastic Syndromes / Smith-Magenis Syndrome / Thrombocytopenias2
2CompletedSupportive CareMyelodysplastic Syndromes / Thrombocytopenias1
2CompletedTreatmentIdiopathic Thrombocytopenic Purpura (ITP)2
2CompletedTreatmentMyelodysplastic Syndromes / Refractory Cytopenias / Smith-Magenis Syndrome / Thrombocytopenias1
2CompletedTreatmentThrombocytopenia in Subjects With Immune (Idiopathic) Thrombocytopenic Purpura (ITP)1
2RecruitingTreatmentGlioblastomas / Thrombocytopenias1
2RecruitingTreatmentIsolated Chemotherapy-induced Thrombocytopenia1
2RecruitingTreatmentMyelodysplastic Syndromes1
2TerminatedSupportive CareRefractory Multiple Myeloma / Stage I Multiple Myeloma / Stage II Multiple Myeloma / Stage III Multiple Myeloma / Thrombocytopenias1
2TerminatedTreatmentHepatitis C Infection / Thrombocytopenias1
2Unknown StatusPreventionNon-Hodgkin's Lymphoma (NHL)1
2Unknown StatusTreatmentImmune Thrombocytopenia1
2, 3Active Not RecruitingTreatmentAplastic Anaemia (AA)1
2, 3CompletedTreatmentThrombocytopenia in Subjects With Immune (Idiopathic) Thrombocytopenic Purpura (ITP)1
3Active Not RecruitingTreatmentImmune Thrombocytopenia / Immune Thrombocytopenia (ITP)1
3CompletedSupportive CareThrombocytopenia in Pediatric Subjects With Immune (Idiopathic) Thrombocytopenic Purpura (ITP) / Thrombocytopenia in Pediatric Subjects With Immune Idiopathic Thrombocytopenic Purpura ITP1
3CompletedTreatmentIdiopathic Thrombocytopenic Purpura (ITP)1
3CompletedTreatmentIdiopathic Thrombocytopenic Purpura (ITP) / Immune Thrombocytopenia / Thrombocytopenia in Pediatric Subjects With Immune (Idiopathic) Thrombocytopenic Purpura (ITP) / Thrombocytopenia in Subjects With Immune (Idiopathic) Thrombocytopenic Purpura (ITP) / Thrombocytopenias / Thrombocytopenic Purpura1
3CompletedTreatmentIdiopathic Thrombocytopenic Purpura (ITP) / Thrombocytopenia in Subjects With Immune (Idiopathic) Thrombocytopenic Purpura (ITP) / Thrombocytopenias / Thrombocytopenic Purpura1
3CompletedTreatmentIdiopathic Thrombocytopenic Purpura (ITP) / Thrombocytopenias3
3CompletedTreatmentIdiopathic Thrombocytopenic Purpura (ITP) / Thrombocytopenias / Thrombocytopenic Purpura1
3CompletedTreatmentImmune Thrombocytopenia1
4CompletedTreatmentIdiopathic Thrombocytopenic Purpura (ITP) / Thrombocytopenias1
4RecruitingTreatmentImmune Thrombocytopenia1
Not AvailableCompletedNot AvailableImmune Thrombocytopenia1
Not AvailableCompletedNot AvailableImmune Thrombocytopenic Purpura ( ITP )1
Not AvailableCompletedNot AvailableThrombocytopenias1
Not AvailableCompletedTreatmentHematology / Myelodysplastic Syndromes / Smith-Magenis Syndrome / Thrombocytopenias1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Injection, powder, for solutionSubcutaneous250 μg
Injection, powder, for solutionSubcutaneous500 μg
Injection, powder, lyophilized, for solutionSubcutaneous250 ug/.5mL
Injection, powder, lyophilized, for solutionSubcutaneous500 ug/mL
Powder, for solutionSubcutaneous250 mcg
Powder, for solutionSubcutaneous500 mcg
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available

Taxonomy

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

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
Transmembrane signaling receptor activity
Specific Function
Receptor for thrombopoietin. May represent a regulatory molecule specific for TPO-R-dependent immune responses.
Gene Name
MPL
Uniprot ID
P40238
Uniprot Name
Thrombopoietin receptor
Molecular Weight
71244.08 Da
References
  1. Krzyzanski W, Sutjandra L, Perez-Ruixo JJ, Sloey B, Chow AT, Wang YM: Pharmacokinetic and pharmacodynamic modeling of romiplostim in animals. Pharm Res. 2013 Mar;30(3):655-69. doi: 10.1007/s11095-012-0894-2. Epub 2012 Dec 19. [PubMed:23250851]

Drug created on November 18, 2007 11:23 / Updated on November 19, 2017 20:33