Volanesorsen

Identification

Summary

Volanesorsen is an antisense oligonucleotide indicated to treat familial chylomicronemia.

Brand Names
Waylivra
Generic Name
Volanesorsen
DrugBank Accession Number
DB15067
Background

Volanesorsen is an antisense oligonucleotide that binds to apoC-III mRNA to prevent its translation.2 It is indicated to treat familial chylomicronemia, a genetic condition that prevents breakdown of triglycerides and chylomicrons.2 This drug is not commonly prescribed as it is used as an adjunct to diet in patients at high risk for pancreatitis, who have had inadequate response to triglyceride lowering therapy.2

Volanesorsen was granted a conditional approval by the European Medicines Agency.2

Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Gene Therapies
Antisense oligonucleotides
Synonyms
  • Volanesorsen
External IDs
  • ISIS 304801

Pharmacology

Indication

Volanesorsen is conditionally approved by the EMA as an adjunct to diet in adults with familial chylomicronemia, at high risk for pancreatitis, and who have had an inadequate response to diet and triglyceride lowering therapy.2

Pharmacology
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Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
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Pharmacodynamics

Volanesorsen is an antisense oligonucleotide that prevents the translation of apoC-III.1,2 It has a long duration of action as it has a half life of >2 weeks.2 Patients should be counselled regarding the risk of thrombocytopenia, raised LDL-C levels, renal toxicity, hepatotoxicity, and immunogenicity.2

Mechanism of action

Volanesorsen is an antisense oligonucleotide that binds to apoC-III mRNA, leading to its degradation, and preventing translation of apoC-III protein.2 Normally, apoC-III would inhibit triglyceride metabolism and hepatic clearance of chylomicrons.2 Preventing translation of apoC-III allows for metabolism and breakdown of these triglycerides and chylomicrons.2

TargetActionsOrganism
AApolipoprotein C-III
inhibitor
antisense oligonucleotide
Humans
Absorption

Volanesorsen is approximately 80% bioavailable.2 A 285mg dose given weekly reaches a Cmax of 8.92 µg/mL, with an AUC of 136 µg*h/mL.2

Volume of distribution

The volume of distribution at steady state is 330 L in patients with familial chylomicronemia.2

Protein binding

Volanesorsen is >98% bound to proteins in plasma.1,2 Though the exact proteins have not been identified.1

Metabolism

Volanesorsen is metabolized by endonucleases and exonucleases in a nonspecific manner.2 The unchanged parent drug is 26% recovered in the urine and pentamer to heptamer sized metabolites account for 55% of urinary recovery.[L16621

Route of elimination

Volanesorsen is predominantly eliminated in the urine, though <3% of a dose was recovered within 24 hours.2

Half-life

Volanesorsen has a half life of >2 weeks.2

Clearance

The exact rate of clearance of volanesorsen is unknown, however it is rapidly distributed to tissues and very slowly eliminated.2

Adverse Effects
Adverseeffects
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Toxicity

Data regarding overdose are not readily available.2 However, symptoms are likely to involve injection site reactions and constitutional symptomns.2 Treat patients with symptomatic and supportive care.2

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
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.
Not Available
Food Interactions
No interactions found.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Volanesorsen sodium6JON30SLDT1573402-50-2Not applicable
International/Other Brands
Waylivra
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
WaylivraInjection, solution285 mgSubcutaneousAkcea Therapeutics Ireland Limited2020-12-16Not applicableEU flag
WaylivraInjection, solution285 mgSubcutaneousAkcea Therapeutics Ireland Limited2020-12-16Not applicableEU flag

Categories

Drug Categories
Classification
Not classified
Affected organisms
Not Available

Chemical Identifiers

UNII
2O4BE0K238
CAS number
915430-78-3

References

General References
  1. Post N, Yu R, Greenlee S, Gaus H, Hurh E, Matson J, Wang Y: Metabolism and Disposition of Volanesorsen, a 2'-O-(2 methoxyethyl) Antisense Oligonucleotide, Across Species. Drug Metab Dispos. 2019 Oct;47(10):1164-1173. doi: 10.1124/dmd.119.087395. Epub 2019 Jul 26. [Article]
  2. EMA Summary of Product Characteristics: Waylivra Volanesorsen Subcutaneous Injection [Link]
KEGG Drug
D11648
Wikipedia
Volanesorsen

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3CompletedTreatmentFamilial Chylomicronemia Syndrome (FCS)1
3CompletedTreatmentFamilial Chylomicronemia Syndrome (FCS) / Lipoprotein Lipase Deficiency / Type 1 Hyperlipoproteinemia1
3CompletedTreatmentHypertriglyceridemias1
2CompletedTreatmentLipodystrophies1
2, 3Active Not RecruitingTreatmentLipodystrophy, Familial Partial1
1CompletedOtherCardiovascular Abnormalities1
Not AvailableNo Longer AvailableNot AvailableFamilial Chylomicronemia1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Injection, solutionParenteral; Subcutaneous285 MG
Injection, solutionSubcutaneous285 mg
Prices
Not Available
Patents
Not Available

Properties

State
Liquid
Experimental Properties
Not Available

Targets

Drugtargets2
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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
Antisense oligonucleotide
General Function
Phospholipid binding
Specific Function
Component of triglyceride-rich very low density lipoproteins (VLDL) and high density lipoproteins (HDL) in plasma. Plays a multifaceted role in triglyceride homeostasis. Intracellularly, promotes h...
Gene Name
APOC3
Uniprot ID
P02656
Uniprot Name
Apolipoprotein C-III
Molecular Weight
10852.19 Da
References
  1. Post N, Yu R, Greenlee S, Gaus H, Hurh E, Matson J, Wang Y: Metabolism and Disposition of Volanesorsen, a 2'-O-(2 methoxyethyl) Antisense Oligonucleotide, Across Species. Drug Metab Dispos. 2019 Oct;47(10):1164-1173. doi: 10.1124/dmd.119.087395. Epub 2019 Jul 26. [Article]
  2. EMA Summary of Product Characteristics: Waylivra Volanesorsen Subcutaneous Injection [Link]

Drug created on May 20, 2019 14:46 / Updated on February 21, 2021 18:55