Identification

Name
Peginesatide
Accession Number
DB08894
Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Peptides
Description

Peginesatide is a synthetic peptide attached to polyethylene glycol for the treatment of anemia. The polyethylene glycol moiety helps make the drug less immunogenic and prolongs its plasma half-life. Chemically, peginesatide is designed to mimic the pharmacological activity of erythropoietin, but is not a replica of the structure itself. Peginesatide consists of two 21-amino acid chains that are covalently bonded by a linker derived from iminodiacetic acid and β-alanine. FDA approved March 27, 2012.

Protein chemical formula
Not Available
Protein average weight
Not Available
Sequences
Not Available
Synonyms
  • Erythropoiesis-Stimulating Agent (ESA)
  • Hematide
Product Ingredients
IngredientUNIICASInChI Key
Peginesatide acetate44STI720CW1185870-58-9Not applicable
International/Other Brands
Omontys (Takeda Pharmaceutical Company Ltd. )
Categories
UNII
JX56W9N61Q
CAS number
913976-27-9

Pharmacology

Indication

Peginesatide is used for the treatment of anemia due to chronic kidney disease (CKD) in adult patients on dialysis

Structured Indications
Not Available
Pharmacodynamics

Peginesatide increases the reticulocyte count and levels of hemoglobin. It also increases RBC count, hematocrit, and soluble transferrin receptor protein in a dose-dependent manner.

Mechanism of action

Peginesatide binds to and activates the human erythropoietin receptor and stimulates erythropoiesis in human red cell precursors in vitro.

TargetActionsOrganism
AErythropoietin receptor
stimulator
Human
Absorption

Tmax, SubQ dose = 48 hours;
Bioavailability, SubQ dose = 46%; Peginesatide does not accumulate when administered every 4 weeks following intravenous or subcutaneous administration.

Volume of distribution

IV dose, dialysis patients = 34.9 ± 13.8 mL/kg;

Protein binding

Peginesatide does not bind to serum albumin or lipoprotein as demonstrated in in-vitro studies.

Metabolism

Preclinical radiolabeled peginesatide study indicated that peginesatide is not metabolized.

Route of elimination

Peginesatide administered intravenously or subcutaneously is primarily excreted via urine. Most of the excreted dose is in the form of unchanged drug. Elimination from the plasma is biphasic and rapid from vascular compartments. In contrast, the drug is selectively retained in sites of erythropoiesis like the bone marrow.

Half life

IV dose, healthy subjects = 25.0 ± 7.6 hours; SubQ, healthy subjects = 53.0 ± 17.7 hours; IV dose, dialysis patients = 47.9 ± 16.5 hours;

Clearance

Systemic clearance, IV dose, dialysis patients = 0.5 ± 0.2 mL/hr•kg

Toxicity

The most common adverse events (≥10%) are dyspnea, diarrhea, nausea, cough, and arteriovenous fistula site complication.

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. Schmid H: Peginesatide for the treatment of renal disease-induced anemia. Expert Opin Pharmacother. 2013 May;14(7):937-48. doi: 10.1517/14656566.2013.780695. Epub 2013 Mar 18. [PubMed:23506424]
  2. Woodburn KW, Holmes CP, Wilson SD, Fong KL, Press RJ, Moriya Y, Tagawa Y: Absorption, distribution, metabolism and excretion of peginesatide, a novel erythropoiesis-stimulating agent, in rats. Xenobiotica. 2012 Jul;42(7):660-70. doi: 10.3109/00498254.2011.649310. Epub 2011 Dec 22. [PubMed:22188389]
  3. Woodburn KW, Fong KL, Wilson SD, Sloneker S, Strzemienski P, Solon E, Moriya Y, Tagawa Y: Peginesatide clearance, distribution, metabolism, and excretion in monkeys following intravenous administration. Drug Metab Dispos. 2013 Apr;41(4):774-84. doi: 10.1124/dmd.112.048033. Epub 2013 Jan 14. [PubMed:23318685]
External Links
KEGG Drug
D09947
PubChem Substance
175427138
ChEBI
66895
ChEMBL
CHEMBL2107866
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Peginesatide
ATC Codes
B03XA04 — Peginesatide
FDA label
Download (272 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentAnemias / Cancers / Chronic Kidney Disease (CKD) / Chronic Renal Failure (CRF)1
1TerminatedTreatmentAnemias1
2CompletedTreatmentAnemias2
2CompletedTreatmentAnemias / Chronic Kidney Disease (CKD) / Chronic Renal Failure (CRF)4
2CompletedTreatmentAnemias / Chronic Kidney Disease (CKD) / Chronic Renal Failure (CRF) / Pure Red Cell Aplasia1
2CompletedTreatmentCancers / Chemotherapy Induced Anemia1
2TerminatedTreatmentAnemias / Chronic Kidney Disease (CKD) / Chronic Renal Failure (CRF)3
3CompletedTreatmentAnemias / Chronic Kidney Disease (CKD)1
3CompletedTreatmentAnemias / Chronic Kidney Disease (CKD) / Chronic Renal Failure (CRF)4
4TerminatedTreatmentAnemias1
Not AvailableNot Yet RecruitingOtherAnemias / End Stage Renal Disease (ESRD)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US7084245No2004-05-122024-05-12Us
US7414105No2004-05-122024-05-12Us
US7550433No2006-06-022026-06-02Us
US7919461No2006-06-022026-06-02Us
US7528104No2004-05-122024-05-12Us
US7919118No2004-05-122024-05-12Us

Properties

State
Liquid
Experimental Properties
PropertyValueSource

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
Stimulator
General Function
Identical protein binding
Specific Function
Receptor for erythropoietin. Mediates erythropoietin-induced erythroblast proliferation and differentiation. Upon EPO stimulation, EPOR dimerizes triggering the JAK2/STAT5 signaling cascade. In som...
Gene Name
EPOR
Uniprot ID
P19235
Uniprot Name
Erythropoietin receptor
Molecular Weight
55064.725 Da
References
  1. Woodburn KW, Fong KL, Wilson SD, Sloneker S, Strzemienski P, Solon E, Moriya Y, Tagawa Y: Peginesatide clearance, distribution, metabolism, and excretion in monkeys following intravenous administration. Drug Metab Dispos. 2013 Apr;41(4):774-84. doi: 10.1124/dmd.112.048033. Epub 2013 Jan 14. [PubMed:23318685]

Drug created on June 01, 2013 16:45 / Updated on November 06, 2017 06:46