Etranacogene dezaparvovec

Identification

Summary

Etranacogene dezaparvovec is an adeno-associated virus vector-based gene therapy used for the treatment of hemophilia B (congenital factor IX deficiency).

Generic Name
Etranacogene dezaparvovec
DrugBank Accession Number
DB16791
Background

Hemophilia B - also called factor IX deficiency or Christmas disease - is an X-linked genetic disorder resulting in an absence or deficiency of clotting factor IX.3 Clotting factors, including factor IX, are necessary components of the signaling cascade responsible for blood clotting and subsequent wound healing.4 Symptoms of hemophilia B, therefore, involve a heightened susceptibility to bleeding episodes - in mild cases, bleeding may only occur after injury, while in more severe cases bleeding may occur after a minor injury or even spontaneously.4

Hemophilia B is the second most common type of hemophilia,4 with a prevalence of approximately one in 40,000.2 Men are most likely to experience symptomatic illness due to the X-linked provenance of the disorder.2 Treatment of hemophilia B primarily involves the routine replacement of factor IX using recombinant or donor-derived factor IX products that, while effective, may be burdensome for the patient due to the requirement of routine intravenous infusions.2,4

Etranacogene dezaparvovec (Hemgenix, CSL Bering LLC) is a gene therapy for the treatment of hemophilia B that provides a new treatment modality for its patients. The therapy involves a one-time infusion of a viral vector carrying a codon-optimized DNA sequence of the gain-of-function Padua variant of human Factor IX controlled by a liver-specific promotor 1.1 It delivers a copy of the deficient gene that results in cell transduction and an eventual increase in circulating factor IX activity.1 Etranacogene dezaparvovec was approved by the FDA in November 2022 for the treatment of select patients with hemophilia B, becoming the first gene therapy approved for this indication.2 It is additionally notable for its cost per treatment - approximately 3.5 million USD - earning it the title of most expensive drug in the world.5 In December 2022, the EMA's Committee for Medicinal Products for Human Use (CHMP) recommended etranacogene dezaparvovec be granted marketing authorization for the treatment of severe and moderately severe Haemophilia B.6 Etranacogene dezaparvovec was approved by the EMA in February 20237,8 and by Health Canada in October 2023.9

Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Gene Therapies
Other gene therapies
Synonyms
  • AAV5-hFIXco-Padua
  • Etranacogene dezaparvovec
External IDs
  • AMT-061

Pharmacology

Indication

Etranacogene dezaparvovec (Hemgenix) is indicated in the United States for the treatment of adults with hemophilia B who fit one of the following criteria:1

  • Currently use factor IX prophylaxis therapy
  • Have current or historical life-threatening hemorrhage
  • Have repeated, serious spontaneous bleeding episodes

In the EU, etranacogene dezaparvovec for the treatment of severe and moderately severe hemophilia B in adult patients without a history of Factor IX inhibitors.8 In Canada, etranacogene dezaparvovec is indicated for adult patients with hemophilia B who require routine prophylaxis to prevent or reduce the frequency of bleeding episodes.10

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Treatment ofHemophilia b•••••••••••••••••••••• •••••• •• ••••••••••• ••••••••••••••••• ••••••••••
Treatment ofHemophilia b•••••••••••••••••••••• •••••• •• ••••••••••• ••••••••••••••••• ••••••••••
Treatment ofHemophilia b•••••••••••••••••••••••• ••••••••• •••••••• •••••••••••••••••• ••••••••••
Treatment ofHemophilia b•••••••••••••••••••••••• •• ••••••• •••••••••••••••••••• ••••••••••
Treatment ofHemophilia b•••••••••••••••••••••••• •••••••••••••••••••• ••••••••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

Following a single intravenous infusion, median factor IX activity increased to 23.7% of normal by week 3, 33.8% at 3 months, 37.3% at 6 months, and peaked at 39.9% at 12 months.1 After 24 months, median activity remained at 33.9% of normal.1

Mechanism of action

Etranacogene dezaparvovec is a non-replicating recombinant adeno-associated virus serotype 5 (AAV5) vector containing a codon-optimized DNA sequence of the gain-of-function Padua variant of human Factor IX (variant R338L) controlled by a liver-specific promotor 1.1 It is administered by a single intravenous infusion and delivers a copy of the gene in which hemophilia B patients are defective, leading to cell transduction and an eventual increase in circulating activity levels of factor IX.1

Absorption

Not Available

Volume of distribution

In a study to evaluate the biodistribution of etranacogene dezaparvovec in male mice and non-human primates, the highest levels of vector DNA were detected in the liver and adrenal glands, although it was also detected in all reproductive tissues examined.1

Protein binding

Not Available

Metabolism
Not Available
Route of elimination

Not Available

Half-life

Not Available

Clearance

In a clinical study, the maximum time to clearance of vector DNA was 22 weeks for urine, 26 weeks for saliva and nasal secretions, 40 weeks for feces, 52 weeks for semen, and 159 weeks for blood.1

Adverse Effects
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Toxicity

Not Available

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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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
HemgenixInjection, suspension; Kit1013 {GC}/1IntravenousCsl Behring2022-11-22Not applicableUS flag
HemgenixInjection, suspension; Kit1013 {GC}/1IntravenousCsl Behring2022-11-22Not applicableUS flag
HemgenixInjection, suspension; Kit1013 {GC}/1IntravenousCsl Behring2022-11-22Not applicableUS flag
HemgenixInjection, suspension; Kit1013 {GC}/1IntravenousCsl Behring2022-11-22Not applicableUS flag
HemgenixInjection, suspension; Kit1013 {GC}/1IntravenousCsl Behring2022-11-22Not applicableUS flag

Categories

Drug Categories
Classification
Not classified
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
Z5XCD5Q9RL
CAS number
2156583-26-3

References

General References
  1. FDA Approved Drug Products: Hemgenix (etranacogene dezaparvovec-drlb) suspension for intravenous infusion [Link]
  2. FDA News Release: FDA Approves First Gene Therapy to Treat Adults with Hemophilia B [Link]
  3. National Hemophilia Foundation: Hemophilia B [Link]
  4. National Organization for Rare Disorders (NORD): Hemophilia B [Link]
  5. CNN: FDA approves $3.5 million treatment for hemophilia, now the most expensive drug in the world [Link]
  6. EMA Summary of Opinion: Hemgenix (etranacogene dezaparvovec) [Link]
  7. PR NewsWire: First Gene Therapy for Hemophilia B, CSL's HEMGENIX, Approved by the European Commission [Link]
  8. EMA Summary of Product Characteristics: HEMGENIX (etranacogene dezaparvovec) concentrate for solution for infusion [Link]
  9. Canadian Hemophilia Society (CHS) Contact: Health Canada approves Hemgenix gene therapy for hemophilia B [Link]
  10. Health Canada Product Monograph: Hemgenix (etranacogene dezaparvovec) suspension for intravenous infusion [Link]
RxNav
2626727
Wikipedia
Etranacogene_dezaparvovec

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedTreatmentHemophilia B1
1, 2CompletedTreatmentHemophilia B1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Injection, solution, concentrateIntravenous10000000000000 gc/ml
Injection, suspension; kitIntravenous1013 {GC}/1
SuspensionIntravenous10000000000000 genome copies / mL
Prices
Not Available
Patents
Not Available

Properties

State
Liquid
Experimental Properties
Not Available

Drug created at May 10, 2022 20:13 / Updated at November 25, 2023 12:39