Pegaptanib

Identification

Name
Pegaptanib
Accession Number
DB04895
Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Nucleic Acid Based Therapies
Oligonucleotides
Description

Pegaptanib is a polynucleotide aptamer. Pegaptanib specifically binds to VEGF 165, a protein that plays a critical role in angiogenesis (the formation of new blood vessels) and increased permeability (leakage from blood vessels), two of the primary pathological processes responsible for the vision loss associated with neovascular AMD. [Wikipedia]

Synonyms
  • EYE 001
  • NX 1838
  • NX1838
  • Pegaptanib Octasodium
  • Pegaptanib sodium
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
MacugenSolution0.3 mgIntravitrealPfizer2005-08-262014-09-04Canada
MacugenInjection, solution3.47 mg/mLIntravitrealBauch & Lomb Incorporated2004-12-17Not applicableUs
MacugenInjection, solution0.3 mgIntravitrealPharma Swiss Ceska Republika S.R.O2006-01-31Not applicableEu
Categories
UNII
3HP012Q0FH
CAS number
222716-86-1

Pharmacology

Indication

For the treatment of neovascular (wet) age-related macular degeneration.

Structured Indications
Pharmacodynamics

Pegaptanib is a selective vascular endothelial growth factor (VEGF) antagonist. VEGF is a secreted protein that selectively binds and activates its receptors located primarily on the surface of vascular endothelial cells. VEGF induces angiogenesis, and increases vascular permeability and inflammation, all of which are thought to contribute to the progression of the neovascular (wet) form of age-related macular degeneration (AMD), a leading cause of blindness. VEGF has been implicated in blood retinal barrier breakdown and pathological ocular neovascularization.

Mechanism of action

Pegaptanib sodium is a pegylated aptamer, a modified oligonucleotide, which adopts a three- dimensional conformation that enables it to bind to extracellular VEGF with high affinity and selectivity. Pegaptanib sodium binds to the major pathological VEGF isoform, extracellular VEGF165, with high affinity (Kd = 200 pM) and specificity, thereby inhibiting VEGF165 binding to its VEGF receptors. In contrast virtually no binding of the non-pegylated aptamer to VEGF121 or the VEGF -related proteins VEGF-B, VEGF-C and placental growth factor (PlGF) was detected using invitro filter binding assays. Pegaptanib sodium does not bind significantly to VEGF121. In animal models, VEGF164 (the rodent counterpart of human VEGF165) was specifically upregulated in disease. The selective inhibition of VEGF164 with pegaptanib sodium proved as effective at suppressing pathological neovascularization as pan-VEGF inhibition7, however pegaptanib sodium spared the normal vasculature whereas pan-VEGF inhibition did not.

TargetActionsOrganism
UNeuropilin-1Not AvailableHuman
Absorption

In animals, pegaptanib is slowly absorbed into the systemic circulation from the eye after intravitreous administration.

Volume of distribution

It is distributed into vitreous fluid, retina, aqueous fluid, and kidneys. As well, it has been shown to cross the placenta in mice but whether or not it crosses the placenta in humans is unknown.

Protein binding
Not Available
Metabolism

Based on preclinical data, pegaptanib is metabolized by endo- and exonucleases.

Route of elimination

It is excreted primarily in urine as unchanged drug and also as metabolites. There is no dosage adjustment required for patients with renal impairment although it must be noted that not many studies have looked at patients with a creatinine clearance of 30mL/min.

Half life

In humans, after a 3 mg monocular dose (10 times the recommended dose), the average (± standard deviation) apparent plasma half-life of pegaptanib is 10 (± 4) days.

Clearance
Not Available
Toxicity

It is not known if pegaptanib is safe in pregnant women or if it is excreted in breast milk. Likewise, no studies have been done in the pediatric population. Most adverse events elated to the drug are ocular however non-ocular adverse events related to the drug or the injection procedure also occurred, among which headaches and rhinorrhoea appeared in more than 1% of patients. Pegaptanib is contraindicated when the patient has an ocular or periocular infection.

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

Interactions

Drug Interactions
DrugInteractionDrug group
PegloticaseThe therapeutic efficacy of Pegaptanib can be decreased when used in combination with Pegloticase.Approved
Food Interactions
Not Available

References

General References
  1. Vinores SA: Pegaptanib in the treatment of wet, age-related macular degeneration. Int J Nanomedicine. 2006;1(3):263-8. [PubMed:17717967]
  2. Wylegala E, Teper SJ: [VEGF in age-related macular degeneration. Part II. VEGF inhibitors use in age-related macular degeneration treatment]. Klin Oczna. 2007;109(1-3):97-100. [PubMed:17687925]
  3. Bakri SJ, Pulido JS, McCannel CA, Hodge DO, Diehl N, Hillemeier J: Immediate intraocular pressure changes following intravitreal injections of triamcinolone, pegaptanib, and bevacizumab. Eye (Lond). 2009 Jan;23(1):181-5. Epub 2007 Aug 10. [PubMed:17693999]
External Links
PubChem Substance
46504497
Therapeutic Targets Database
DAP001259
PharmGKB
PA164771236
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Pegaptanib
ATC Codes
S01LA03 — Pegaptanib
FDA label
Download (99.6 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentPDR1
1, 2TerminatedTreatmentCystoid Macular Edema2
2CompletedTreatmentDiabetic Macular Edema (DME)1
2CompletedTreatmentMacular Degeneration3
2CompletedTreatmentRetinal Vein Occlusions(RVO)1
2, 3CompletedTreatmentAge-Related Macular Degeneration (ARMD)2
2, 3CompletedTreatmentMacular Edema Associated With Diabetes Mellitus1
3CompletedTreatmentAnti- VGF Inhibitor / Diabetic Macular Edema (DME) / Retinopathy, Diabetic1
3CompletedTreatmentDiabetic Mellitus / Macular Edema (ME) / Retinal Diseases1
3CompletedTreatmentMacular Degeneration1
3CompletedTreatmentMacular Degeneration / Subfoveal Choroidal Neovascularization1
3Unknown StatusTreatmentAge-Related Macular Degeneration (ARMD)1
3WithdrawnTreatmentProliferative Diabetic Retinopathy (PDR)1
4CompletedTreatmentBranch Retinal Vein Occlusion1
4CompletedTreatmentDiabetic Macular Edema (DME)2
4CompletedTreatmentMacular Degeneration1
4RecruitingOtherAge-Related Macular Degeneration (ARMD) / Diabetic Macular Edema (DME) / Retinal Vein Occlusions(RVO)1
4RecruitingTreatmentMacular Diseases1
4TerminatedTreatmentAge Related Macular Degeneration (AMD) / Choroidal Neovascularization (CNV) / Macular Degeneration1
4TerminatedTreatmentAge-Related Macular Degeneration (ARMD)1
4TerminatedTreatmentMacular Degeneration1
4Unknown StatusTreatmentAge-Related Macular Degeneration (AMD)1
4Unknown StatusTreatmentProliferative Diabetic Retinopathy (PDR)1
4WithdrawnNot AvailableNeovascular Age-Related Macular Degeneration1
Not AvailableAvailableNot AvailableDiabetic Macular Edema (DME)1
Not AvailableCompletedNot AvailableAge-Related Macular Degeneration (ARMD) / Macular Degeneration / Neovascular Macular Degeneration1
Not AvailableCompletedNot AvailableMacular Degeneration2
Not AvailableCompletedNot AvailableNeovascular Age-Related Macular Degeneration2
Not AvailableCompletedDiagnosticDiabetic Macular Edema (DME) / Proliferative Diabetic Retinopathy (PDR)1
Not AvailableCompletedTreatmentCystoid Macular Edema / Uveitis1
Not AvailableCompletedTreatmentMacular Degeneration1
Not AvailableRecruitingNot AvailableMacular Diseases1
Not AvailableTerminatedTreatmentHistoplasmosis retinitis / Subfoveal Choroidal Neovascularization1
Not AvailableWithdrawnTreatmentMyopic Choroidal Neovascular Membrane1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Dosage forms
FormRouteStrength
Injection, solutionIntravitreal0.3 mg
Injection, solutionIntravitreal3.47 mg/mL
SolutionIntravitreal0.3 mg
Prices
Unit descriptionCostUnit
Macugen 0.3 mg/0.09 ml1194.0USD vial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US6147204No1993-06-112010-06-11Us
CA2269072No2006-02-142017-10-17Canada
US6011020No1997-01-042017-01-04Us
US5932462No1996-08-032016-08-03Us

Properties

State
Liquid
Experimental Properties
Not Available

Taxonomy

Classification
Not classified

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Vascular endothelial growth factor-activated receptor activity
Specific Function
The membrane-bound isoform 1 is a receptor involved in the development of the cardiovascular system, in angiogenesis, in the formation of certain neuronal circuits and in organogenesis outside the ...
Gene Name
NRP1
Uniprot ID
O14786
Uniprot Name
Neuropilin-1
Molecular Weight
103133.62 Da
References
  1. Vinores SA: Pegaptanib in the treatment of wet, age-related macular degeneration. Int J Nanomedicine. 2006;1(3):263-8. [PubMed:17717967]

Drug created on October 21, 2007 16:23 / Updated on November 06, 2017 06:45