Identification

Summary

Bulevirtide is a drug for the treatment of chronic Hepatitis D infection in adults with compensated liver disease.

Brand Names
Hepcludex
Generic Name
Bulevirtide
DrugBank Accession Number
DB15248
Background

Hepatitis D is considered the most severe type of viral hepatitis and leads to the rapid development of cirrhosis, severe decompensation of liver function, and an increased risk of mortality.3,9 Until recently, there have been extremely limited treatments available for Hepatitis D infection.1

Bulevirtide, also known as Hepcludex, is a first-in-class entry inhibitor for the treatment of chronic Hepatitis D infection developed by MYR Pharmaceuticals, now part of Gilead. It was first approved for use in the EU on May 28, 2020; bulevirtide has been granted PRIME scheme eligibility and Orphan Drug Designation by the European Medicines Agency.5 In the USA, bulevirtide has been granted Orphan Drug Designation and Breakthrough Therapy Designation.11,12 Due to potentially beneficial synergistic effects in treating chronic Hepatitis D, bulevirtide is also under investigation in clinical trial NCT03852433 (Phase 2b Study of Bulevirtide With Peginterferon Alfa-2a) in Patients With CHD. Completion of this clinical trial is anticipated in early 2023.10

Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Peptides
Protein Chemical Formula
Not Available
Protein Average Weight
Not Available
Sequences
Not Available
Synonyms
  • Bulevirtide

Pharmacology

Indication

Bulevirtide is indicated for the treatment of chronic Hepatitis D infection in HDV-RNA positive adult patients with compensated liver disease.5

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Associated Conditions
Contraindications & Blackbox Warnings
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Pharmacodynamics

Bulevirtide prevents Hepatitis D entry into cells. It is effective in the reduction of Hepatitis D virus (HDV) RNA levels and improvement of liver inflammation in cases of Hepatitis D infection.5,6,11

Mechanism of action

The sodium taurocholate co-transporting polypeptide (NTCP) serves to transport bile acids in the sodium salt form to the liver from the portal circulation. It is an important component of enterohepatic circulation. The Hepatitis D virus replicates independently within liver cells but requires the hepatitis B surface antigen in order to propagate. Hepatitis B and D viruses enter hepatocytes through the binding of NTCP (sodium/taurocholate cotransporting polypeptide) to the Hepatitis B virus preS1 surface protein domain.11

Bulevirtide binds and subsequently inactivates the hepatitis B (HBV) and HDV receptors on hepatocytes. Bulevirtide blocks the NTCP binding site, subsequently blocking the entry of the viruses into cells. This prevents viral entry and replication, reducing symptoms of Hepatitis D infection.11

TargetActionsOrganism
ASodium/bile acid cotransporter
inhibitor
Humans
Absorption

Human pharmacokinetic data for bulevirtide is limited in the literature. In rats, bulevirtide administered by subcutaneous injection is rapidly absorbed with a Cmax of 4 to 6 hours.5 The estimated bioavailability is 85% in humans, and steady-state concentrations are expected to occur within weeks of initiating treatment.4,13 The AUC for bulevirtide after a 2mg subcutaneous dose was found to be approximately 46 ng/ml.h with a Tmax of 0.5 hours.5

Volume of distribution

The volume of distribution of bulevirtide is estimated to be lower than total body water.13 In animals, bulevirtide distributes into the liver, gastrointestinal tract, kidney, and bladder.5

Protein binding

The plasma protein binding of bulevirtide is >99%,13 and it is primarily bound to albumin.5

Metabolism

To date, metabolism studies have not been conducted on bulevirtide. It is expected to be catabolized by peptidases to smaller peptides and amino acids, with no active metabolites.5,13

Route of elimination

Elimination through target (NTCP) binding is expected to be the main route of elimination for bulevirtide. In healthy volunteers, bulevirtide was not found to be excreted in the urine.13

Half-life

The half-life of bulevirtide ranges between 4 and 7 hours in healthy adults.13

Clearance

The clearance after of bulevirtide after subcutaneous administration (CL/F) in healthy volunteers ranged from 7.98 L/h (±2.02) to 62 L/h (±16.7), depending on the dose administered.5 The clearance of bulevirtide decreases as the dose increases.13

Adverse Effects
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Toxicity

There are no reports of overdose with bulevirtide. In the case of an overdose, monitor the patient and provide supportive treatment.13

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.
DrugInteraction
Adenovirus type 7 vaccine liveThe therapeutic efficacy of Adenovirus type 7 vaccine live can be decreased when used in combination with Bulevirtide.
Anthrax vaccineThe therapeutic efficacy of Anthrax vaccine can be decreased when used in combination with Bulevirtide.
Bacillus calmette-guerin substrain connaught live antigenThe therapeutic efficacy of Bacillus calmette-guerin substrain connaught live antigen can be decreased when used in combination with Bulevirtide.
Bacillus calmette-guerin substrain russian BCG-I live antigenThe therapeutic efficacy of Bacillus calmette-guerin substrain russian BCG-I live antigen can be decreased when used in combination with Bulevirtide.
Bacillus calmette-guerin substrain tice live antigenThe therapeutic efficacy of Bacillus calmette-guerin substrain tice live antigen can be decreased when used in combination with Bulevirtide.
BCG vaccineThe therapeutic efficacy of BCG vaccine can be decreased when used in combination with Bulevirtide.
Human adenovirus e serotype 4 strain cl-68578 antigenThe therapeutic efficacy of Human adenovirus e serotype 4 strain cl-68578 antigen can be decreased when used in combination with Bulevirtide.
Rubella virus vaccineThe therapeutic efficacy of Rubella virus vaccine can be decreased when used in combination with Bulevirtide.
Typhoid Vaccine LiveThe therapeutic efficacy of Typhoid Vaccine Live can be decreased when used in combination with Bulevirtide.
Varicella zoster vaccine (live/attenuated)The therapeutic efficacy of Varicella zoster vaccine (live/attenuated) can be decreased when used in combination with Bulevirtide.
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Food Interactions
No interactions found.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Bulevirtide acetateNot AvailableNot AvailableNot applicable
International/Other Brands
Hepcludex / Myrcludex B
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
HepcludexInjection, powder, for solution2 mgSubcutaneousGilead Sciences Ireland Uc2020-12-16Not applicableEU flag

Categories

ATC Codes
J05AX28 — Bulevirtide
Drug Categories
Chemical TaxonomyProvided by Classyfire
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
Affected organisms
Not Available

Chemical Identifiers

UNII
WKM56H3TLB
CAS number
2012558-47-1

References

General References
  1. Abbas Z, Khan MA, Salih M, Jafri W: Interferon alpha for chronic hepatitis D. Cochrane Database Syst Rev. 2011 Dec 7;(12):CD006002. doi: 10.1002/14651858.CD006002.pub2. [Article]
  2. Kang C, Syed YY: Bulevirtide: First Approval. Drugs. 2020 Oct;80(15):1601-1605. doi: 10.1007/s40265-020-01400-1. [Article]
  3. Rizzetto M: Hepatitis D Virus: Introduction and Epidemiology. Cold Spring Harb Perspect Med. 2015 Jul 1;5(7):a021576. doi: 10.1101/cshperspect.a021576. [Article]
  4. Smolders EJ, Burger DM, Feld JJ, Kiser JJ: Review article: clinical pharmacology of current and investigational hepatitis B virus therapies. Aliment Pharmacol Ther. 2020 Jan;51(2):231-243. doi: 10.1111/apt.15581. Epub 2019 Dec 16. [Article]
  5. EMA Public Assessment Report: Hepcludex (bulevirtide) powder for injectable solution [Link]
  6. PRN Newswire: MYR Pharmaceuticals receives positive CHMP opinion for HEPCLUDEX® (bulevirtide), the First-in-Class Entry Inhibitor for the treatment of chronic hepatitis D infections [Link]
  7. Fierce Biotech: Gilead snaps ups German virology biotech MYR, nabbing a European-approved hepatitis D therapy [Link]
  8. MYR Pharmaceuticals: MYR Pharmaceuticals Receives Positive CHMP Opinion For HEPCLUDEX® (Bulevirtide), The First-In-Class Entry Inhibitor For The Treatment Of Chronic Hepatitis D Infections [Link]
  9. NIH StatPearls: Hepatitis D [Link]
  10. Clinicaltrial.gov: Phase 2b Study of Bulevirtide (With Peginterferon Alfa-2a) in Patients With CHD [Link]
  11. MYR pharma: company page [Link]
  12. AP News: Gilead Sciences to Acquire MYR GmbH [Link]
  13. EMA Summary of Product Characteristics: Bulevirtide [Link]
Wikipedia
Bulevirtide

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3Active Not RecruitingTreatmentChronic Hepatitis Delta1
2Active Not RecruitingTreatmentChronic Hepatitis Delta1
2CompletedTreatmentChronic Viral Hepatitis B With Delta-agent1
Not AvailableRecruitingNot AvailableCirrhosis of the Liver / Hepatitis D / Portal Hypertension / Viral Hepatitis B1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Injection, powder, for solutionSubcutaneous2 mg
Injection, powder, for solutionSubcutaneous2 MG/vial
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available

Targets

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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Virus receptor activity
Specific Function
The hepatic sodium/bile acid uptake system exhibits broad substrate specificity and transports various non-bile acid organic compounds as well. It is strictly dependent on the extracellular presenc...
Gene Name
SLC10A1
Uniprot ID
Q14973
Uniprot Name
Sodium/bile acid cotransporter
Molecular Weight
38118.64 Da
References
  1. Kang C, Syed YY: Bulevirtide: First Approval. Drugs. 2020 Oct;80(15):1601-1605. doi: 10.1007/s40265-020-01400-1. [Article]
  2. EMA Public Assessment Report: Hepcludex (bulevirtide) powder for injectable solution [Link]
  3. MYR pharma: company page [Link]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Binder
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. EMA Public Assessment Report: Hepcludex (bulevirtide) powder for injectable solution [Link]

Drug created at May 20, 2019 15:04 / Updated at October 15, 2021 03:57