Identification

Name
Pegvisomant
Accession Number
DB00082  (BTD00044, BIOD00044)
Type
Biotech
Groups
Approved
Biologic Classification
Protein Based Therapies
Hormones
Description

Pegvisomant is a highly selective growth hormone (GH) receptor antagonist. It is used to treat acromegaly. Unlike dopamine or somatostatin analogs (which inhibit growth hormone secretion), this drug actually blocks the hepatic (GH-mediated) production of insulin like growth factor (IGF-1), which is the main mediator of growth hormone activity.

Protein structure
Db00082
Protein chemical formula
C990H1532N262O300S7
Protein average weight
22129.0 Da
Sequences
>DB00082 sequence
FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPT
PSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEG
IQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIV
QCRSVEGSCGF
Download FASTA Format
Synonyms
Not Available
External IDs
B-2036-PEG / B2036-PEG
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
SomavertInjection, powder, for solution20 mgSubcutaneousPfizer2002-11-13Not applicableEu
SomavertKit10 mg/1mLPharmacia & Upjohn Inc2003-05-25Not applicableUs
SomavertKit; Powder, for solution15 mgSubcutaneousPfizer2006-01-24Not applicableCanada
SomavertKit; Powder, for solution10 mgSubcutaneousPfizer2006-01-24Not applicableCanada
SomavertInjection, powder, for solution25 mgSubcutaneousPfizer2002-11-13Not applicableEu
SomavertKit20 mg/1mLPharmacia & Upjohn Inc2003-05-25Not applicableUs
SomavertKit; Powder, for solution25 mgSubcutaneousPfizer2016-03-10Not applicableCanada
SomavertKit15 mg/1mLPharmacia & Upjohn Inc2016-10-01Not applicableUs
SomavertKit30 mg/1mLPharmacia & Upjohn Inc2014-07-31Not applicableUs
SomavertInjection, powder, for solution10 mgSubcutaneousPfizer2002-11-13Not applicableEu
Categories
UNII
N824AOU5XV
CAS number
218620-50-9

Pharmacology

Indication

Pegvisomant is a growth hormone receptor antagonist used for the treatment of acromegaly.

Associated Conditions
Pharmacodynamics

Somavert is used for the treatment of acromegaly, which arises from excessive IGF-1 levels. Somavert selectively binds to growth hormone (GH) receptors on cell surfaces, where it blocks the binding of endogenous GH, and thus interferes with GH signal transduction. Inhibition of GH action results in decreased serum concentrations of insulin-like growth factor-I (IGF-I), and IGF binding protein-3 (IGFBP-3). This reduces the symptoms of acromegaly.

Mechanism of action

Somavert selectively binds to growth hormone (GH) receptors on cell surfaces, where it blocks the binding of endogenous GH. This leads to the normalization of serum IGF-1 levels.

TargetActionsOrganism
AGrowth hormone receptor
antagonist
Human
Absorption
Not Available
Volume of distribution
  • 7 L
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life

~6 days

Clearance
  • 36 - 28 mL/h [SC doses ranging from 10 to 20 mg/day]
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be increased when combined with Pegvisomant.
(S)-WarfarinThe metabolism of (S)-Warfarin can be increased when combined with Pegvisomant.
2,4-thiazolidinedioneThe risk or severity of hypoglycemia can be increased when Pegvisomant is combined with 2,4-thiazolidinedione.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be increased when combined with Pegvisomant.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be increased when combined with Pegvisomant.
5-androstenedioneThe metabolism of 5-androstenedione can be increased when combined with Pegvisomant.
6-O-benzylguanineThe metabolism of 6-O-benzylguanine can be increased when combined with Pegvisomant.
9-aminocamptothecinThe metabolism of 9-aminocamptothecin can be increased when combined with Pegvisomant.
AbemaciclibThe metabolism of Abemaciclib can be increased when combined with Pegvisomant.
Abicipar PegolThe therapeutic efficacy of Abicipar Pegol can be decreased when used in combination with Pegvisomant.
Food Interactions
Not Available

References

Synthesis Reference

Mandayam J. Narasimhan, John A. Anderson, "Process for the large scale production of human growth hormone by serial secondary suspension culture." U.S. Patent US4124448, issued January, 1963.

US4124448
General References
Not Available
External Links
UniProt
P58756
Genbank
AF374232
PubChem Substance
46505507
ChEMBL
CHEMBL1201515
Therapeutic Targets Database
DAP000286
PharmGKB
PA164749630
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Pegvisomant
ATC Codes
H01AX01 — Pegvisomant
AHFS Codes
  • 68:30.08 — Somatotropin Antagonists
FDA label
Download (864 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0Active Not RecruitingTreatmentAging / Immune System and Related Disorders1
0CompletedTreatmentHuman Growth Hormone Deficiency1
0Unknown StatusTreatmentTraumatic Brain Injury (TBI)1
1CompletedBasic ScienceBioavailability1
1CompletedDiagnosticTraumatic Brain Injury (TBI)1
1CompletedTreatmentInfertilities1
1TerminatedTreatmentCystic Fibrosis (CF)1
1TerminatedTreatmentInfection, Human Immunodeficiency Virus I1
1TerminatedTreatmentNeoplasms, Breast / Neoplasms, Colorectal / Neoplasms, Lung / Prostatic Neoplasms / Sarcomas1
1WithdrawnBasic ScienceDiabetes, Diabetes Mellitus Type 11
1, 2CompletedTreatmentX Linked Hypophosphatemic Rickets1
2CompletedTreatmentAmyotrophic Lateral Sclerosis (ALS)1
2CompletedTreatmentConstitutional Delay of Growth and Development / Pituitary Dwarfism / Short Stature1
2CompletedTreatmentConstitutional Growth Delay / Growth Disorders / Nutrition Disorders1
2CompletedTreatmentCrohn's Disease (CD)1
2CompletedTreatmentCystic Fibrosis (CF)1
2CompletedTreatmentDiabetes Mellitus (DM) / Insulin Resistance / Metabolic Syndromes1
2CompletedTreatmentEnd Stage Renal Disease (ESRD) / Renal Osteodystrophy1
2CompletedTreatmentGonadal Dysgenesis / Turner's Syndrome1
2CompletedTreatmentHuman Growth Hormone Deficiency1
2CompletedTreatmentInfertilities1
2CompletedTreatmentInfertilities / Poor Ovarian Reserve1
2CompletedTreatmentTurner's Syndrome1
2Not Yet RecruitingBasic ScienceTendinopathy1
2RecruitingTreatmentGrowth Hormone Treatment / Human Immunodeficiency Virus (HIV)1
2SuspendedTreatmentChronic Heart Failure (CHF)1
2TerminatedTreatmentHormone Deficiency1
2TerminatedTreatmentInsulin-Like Growth Factor-1 Deficiency1
2WithdrawnTreatmentCrohn's Disease (CD)1
2, 3CompletedNot AvailableHypopituitarism1
2, 3CompletedTreatmentLiver Cirrhosis1
2, 3CompletedTreatmentMinor burns1
2, 3RecruitingTreatmentGrowth Hormone Treatment / Minor burns1
2, 3RecruitingTreatmentMinor burns1
3CompletedNot AvailableDiabetes Mellitus (DM)1
3CompletedDiagnosticChromosome 18 / Human Growth Hormone Deficiency / Loss of Chromosome 18q1
3CompletedTreatmentAcromegaly2
3CompletedTreatmentAdult Onset Growth Hormone Deficiency / Pituitary Disorders1
3CompletedTreatmentChronic Heart Failure (CHF)1
3CompletedTreatmentGrowth Hormone Treatment1
3CompletedTreatmentIdiopathic Short Stature (ISS)1
3CompletedTreatmentMcCune Albright Syndrome / Polyostotic Fibrous Dysplasia1
3CompletedTreatmentTurner's Syndrome1
3RecruitingNot AvailableAtherosclerotic Cardiovascular Diseases1
3RecruitingTreatmentAcromegaly1
3Unknown StatusTreatmentHuman Growth Hormone Deficiency1
3Unknown StatusTreatmentOsteoporosis1
3Unknown StatusTreatmentSpinal Cord Injuries (SCI)1
4Active Not RecruitingTreatmentAcromegaly1
4Active Not RecruitingTreatmentIdiopathic Short Stature (ISS)1
4CompletedNot AvailableSmall For Gestational Age (SGA)1
4CompletedDiagnosticChronic Renal Failure (CRF) / Human Growth Hormone Deficiency1
4CompletedOtherBMI >30 kg/m21
4CompletedPreventionHealthy Volunteers1
4CompletedTreatmentAcromegaly6
4CompletedTreatmentAcromegaly / Quality of Life1
4CompletedTreatmentFemale Infertility Due to Diminished Ovarian Reserve3
4CompletedTreatmentHuman Growth Hormone Deficiency / Panhypopituitarism / Short Stature1
4CompletedTreatmentHuman Growth Hormone Deficiency / Prader-Willi Syndrome1
4CompletedTreatmentHypothyroidism1
4CompletedTreatmentTurner's Syndrome1
4Not Yet RecruitingTreatmentLow Ovarian Reserve1
4RecruitingTreatmentSubfertility1
4TerminatedTreatmentShort Bowel Syndrome (SBS)1
4Unknown StatusDiagnosticAtaxia Telangiectasia (AT) / Growth Failure1
4Unknown StatusDiagnosticChronic Chronic myelogenous leukemia / Short Stature1
4Unknown StatusTreatmentAcromegaly / Heart Failure, Unspecified / Left Ventricular Hypertrophy1
4Unknown StatusTreatmentMetabolic Syndromes1
Not AvailableActive Not RecruitingDiagnosticHuman Growth Hormone Deficiency1
Not AvailableActive Not RecruitingOtherBMI >30 kg/m2 / Osteopenia1
Not AvailableCompletedNot AvailableAcromegaly1
Not AvailableCompletedNot AvailableCardiovascular Disease (CVD)1
Not AvailableCompletedNot AvailableHuman Growth Hormone Deficiency2
Not AvailableCompletedBasic ScienceAcromegaly / Metabolic Diseases1
Not AvailableCompletedBasic ScienceDiabetes, Diabetes Mellitus Type 1 / Ketoacidosis1
Not AvailableCompletedBasic ScienceFatty Liver / Metabolism1
Not AvailableCompletedBasic ScienceHealthy Volunteers2
Not AvailableCompletedBasic ScienceHuman Growth Hormone Deficiency1
Not AvailableCompletedBasic ScienceInsulin Resistance1
Not AvailableCompletedBasic ScienceIntracellular Signaling Peptides and Proteins1
Not AvailableCompletedDiagnosticBMI >30 kg/m21
Not AvailableCompletedTreatmentAcromegaly1
Not AvailableCompletedTreatmentAcromegaly / Impaired Glucose Tolerance (IGT) / Insulin Resistance1
Not AvailableCompletedTreatmentChronic Renal Failure (CRF)1
Not AvailableCompletedTreatmentElderly / Growth Hormone1
Not AvailableCompletedTreatmentGrowth Hormone Secretion Abnormality / Obese1
Not AvailableCompletedTreatmentHIV Lipodystrophy1
Not AvailableCompletedTreatmentHuman Growth Hormone Deficiency / Osteoporosis1
Not AvailableCompletedTreatmentSGA and Growth1
Not AvailableCompletedTreatmentTurner's Syndrome1
Not AvailableCompletedTreatmentWerner's Syndrome1
Not AvailableNot Yet RecruitingTreatmentSmall for Gestational Age1
Not AvailableRecruitingNot AvailableAcromegaly / Osteoporosis Risk1
Not AvailableRecruitingBasic ScienceGrowth Hormone Treatment / Metabolic Diseases1
Not AvailableRecruitingTreatmentAcromegaly1
Not AvailableRecruitingTreatmentNonalcoholic Fatty Liver Disease (NAFLD)1
Not AvailableTerminatedNot AvailableHuman Growth Hormone Deficiency1
Not AvailableUnknown StatusNot AvailableHuman Growth Hormone Deficiency1
Not AvailableUnknown StatusNot AvailableHypopituitary Adults1
Not AvailableUnknown StatusBasic ScienceInteraction Between the GH/IGF-I System and the Immune-system1
Not AvailableUnknown StatusBasic ScienceTurner's Syndrome1
Not AvailableUnknown StatusDiagnosticAdult Onset Growth Hormone Deficiency1
Not AvailableUnknown StatusTreatmentCerebral Palsy With Muscle Wasting / Crohn's Disease (CD) / Human Immunodeficiency Virus (HIV) Infections / Hurler Syndrome (MPS-1) With Short Stature and Muscle Wasting / Juvenile Rheumatoid Arthritis With Muscle Wasting and Short Stature1
Not AvailableUnknown StatusTreatmentCystic Fibrosis (CF)1
Not AvailableWithdrawnOtherShort Stature1
Not AvailableWithdrawnTreatmentOsteoporosis Pseudoglioma Syndrome1

Pharmacoeconomics

Manufacturers
  • Pharmacia and upjohn co
Packagers
  • Hospira Inc.
  • Pfizer Inc.
  • Pharmacia Inc.
Dosage forms
FormRouteStrength
Injection, powder, for solutionSubcutaneous10 mg
Injection, powder, for solutionSubcutaneous15 mg
Injection, powder, for solutionSubcutaneous20 mg
Injection, powder, for solutionSubcutaneous25 mg
Injection, powder, for solutionSubcutaneous30 mg
Kit10 mg/1mL
Kit15 mg/1mL
Kit20 mg/1mL
Kit25 mg/1mL
Kit30 mg/1mL
Kit; powder, for solutionSubcutaneous10 mg
Kit; powder, for solutionSubcutaneous15 mg
Kit; powder, for solutionSubcutaneous20 mg
Kit; powder, for solutionSubcutaneous25 mg
Kit; powder, for solutionSubcutaneous30 mg
Prices
Unit descriptionCostUnit
Somavert 20 mg vial208.38USD vial
Somavert 15 mg vial156.29USD vial
Somavert 10 mg vial104.18USD vial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5350836No1994-09-272011-09-27Us
CA2230492No2009-05-262016-09-20Canada
CA2102129No2003-04-012012-05-01Canada
US6057292No2000-05-022015-09-21Us
US5849535No1998-12-152017-03-25Us

Properties

State
Liquid
Experimental Properties
PropertyValueSource
melting point (°C)76 °C at pH 3.5Gomez-Orellana, I. et al., Protein Sci. 7:1352-1358 (1998)
hydrophobicity-0.411Not Available
isoelectric point5.27Not 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
Antagonist
General Function
Protein kinase binding
Specific Function
Receptor for pituitary gland growth hormone involved in regulating postnatal body growth. On ligand binding, couples to the JAK2/STAT5 pathway (By similarity).The soluble form (GHBP) acts as a rese...
Gene Name
GHR
Uniprot ID
P10912
Uniprot Name
Growth hormone receptor
Molecular Weight
71498.885 Da
References
  1. Moller L, Norrelund H, Jessen N, Flyvbjerg A, Pedersen SB, Gaylinn BD, Liu J, Thorner MO, Moller N, Lunde Jorgensen JO: Impact of growth hormone receptor blockade on substrate metabolism during fasting in healthy subjects. J Clin Endocrinol Metab. 2009 Nov;94(11):4524-32. doi: 10.1210/jc.2009-0381. Epub 2009 Oct 9. [PubMed:19820031]
  2. Paisley AN, Hayden K, Ellis A, Anderson J, Wieringa G, Trainer PJ: Pegvisomant interference in GH assays results in underestimation of GH levels. Eur J Endocrinol. 2007 Mar;156(3):315-9. [PubMed:17322491]
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  4. De Martino MC, Auriemma RS, Brevetti G, Vitale G, Schiano V, Galdiero M, Grasso L, Lombardi G, Colao A, Pivonello R: The treatment with growth hormone receptor antagonist in acromegaly: effect on vascular structure and function in patients resistant to somatostatin analogues. J Endocrinol Invest. 2010 Oct;33(9):663-70. doi: 10.3275/7143. Epub 2010 Jul 1. [PubMed:20595800]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inducer
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Catalyzes the first step in the oxidation of the side chain of sterol intermediates; the 27-hydroxylation of 5-beta-cholestane-3-alpha,7-alpha,12-alpha-triol. Has also a vitamin D3-25-hydroxylase a...
Gene Name
CYP27A1
Uniprot ID
Q02318
Uniprot Name
Sterol 26-hydroxylase, mitochondrial
Molecular Weight
60234.28 Da
References
  1. Araya Z, Tang W, Wikvall K: Hormonal regulation of the human sterol 27-hydroxylase gene CYP27A1. Biochem J. 2003 Jun 1;372(Pt 2):529-34. [PubMed:12597773]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Manganese ion binding
Specific Function
This enzyme has 2 functions: it catalyzes the production of glutamine and 4-aminobutanoate (gamma-aminobutyric acid, GABA), the latter in a pyridoxal phosphate-independent manner (By similarity). E...
Gene Name
GLUL
Uniprot ID
P15104
Uniprot Name
Glutamine synthetase
Molecular Weight
42064.15 Da
References
  1. Nolan EM, Masters JN, Dunn A: Growth hormone regulation of hepatic glutamine synthetase mRNA levels in rats. Mol Cell Endocrinol. 1990 Mar 5;69(2-3):101-10. [PubMed:1970314]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C18
Uniprot ID
P33260
Uniprot Name
Cytochrome P450 2C18
Molecular Weight
55710.075 Da
References
  1. Lofgren S, Baldwin RM, Carleros M, Terelius Y, Fransson-Steen R, Mwinyi J, Waxman DJ, Ingelman-Sundberg M: Regulation of human CYP2C18 and CYP2C19 in transgenic mice: influence of castration, testosterone, and growth hormone. Drug Metab Dispos. 2009 Jul;37(7):1505-12. doi: 10.1124/dmd.109.026963. Epub 2009 Apr 1. [PubMed:19339376]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inducer
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Liddle C, Goodwin BJ, George J, Tapner M, Farrell GC: Separate and interactive regulation of cytochrome P450 3A4 by triiodothyronine, dexamethasone, and growth hormone in cultured hepatocytes. J Clin Endocrinol Metab. 1998 Jul;83(7):2411-6. [PubMed:9661620]
  2. Cheung C, Yu AM, Chen CS, Krausz KW, Byrd LG, Feigenbaum L, Edwards RJ, Waxman DJ, Gonzalez FJ: Growth hormone determines sexual dimorphism of hepatic cytochrome P450 3A4 expression in transgenic mice. J Pharmacol Exp Ther. 2006 Mar;316(3):1328-34. Epub 2005 Nov 16. [PubMed:16291874]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Identical protein binding
Specific Function
Esterase with broad substrate specificity. Contributes to the inactivation of the neurotransmitter acetylcholine. Can degrade neurotoxic organophosphate esters.
Gene Name
BCHE
Uniprot ID
P06276
Uniprot Name
Cholinesterase
Molecular Weight
68417.575 Da
References
  1. Lamartiniere CA: Growth hormone modulates serum cholinesterase. Endocrinology. 1986 Mar;118(3):1252-4. [PubMed:3948777]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Leukotriene-b4 20-monooxygenase activity
Specific Function
Catalyzes the omega- and (omega-1)-hydroxylation of various fatty acids such as laurate, myristate and palmitate. Has little activity toward prostaglandins A1 and E1. Oxidizes arachidonic acid to 2...
Gene Name
CYP4A11
Uniprot ID
Q02928
Uniprot Name
Cytochrome P450 4A11
Molecular Weight
59347.31 Da
References
  1. Savas U, Machemer DE, Hsu MH, Gaynor P, Lasker JM, Tukey RH, Johnson EF: Opposing roles of peroxisome proliferator-activated receptor alpha and growth hormone in the regulation of CYP4A11 expression in a transgenic mouse model. J Biol Chem. 2009 Jun 12;284(24):16541-52. doi: 10.1074/jbc.M902074200. Epub 2009 Apr 14. [PubMed:19366684]

Drug created on June 13, 2005 07:24 / Updated on December 16, 2018 06:35