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
- 915207G
- 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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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Hepatitis d •••••••••••• •••••••••• ••••••• ••• •••••••• - Contraindications & Blackbox Warnings
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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
Target Actions Organism ASodium/bile acid cotransporter inhibitorHumans - 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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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.
Drug Interaction Integrate drug-drug
interactions in your softwareAdenovirus type 7 vaccine live The therapeutic efficacy of Adenovirus type 7 vaccine live can be decreased when used in combination with Bulevirtide. Anthrax vaccine The therapeutic efficacy of Anthrax vaccine can be decreased when used in combination with Bulevirtide. Bacillus calmette-guerin substrain connaught live antigen The 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 antigen The 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 antigen The therapeutic efficacy of Bacillus calmette-guerin substrain tice live antigen can be decreased when used in combination with Bulevirtide. - Food Interactions
- No interactions found.
Products
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Ingredient UNII CAS InChI Key Bulevirtide acetate Not Available Not Available Not applicable - International/Other Brands
- Hepcludex / Myrcludex B
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Hepcludex Injection, powder, for solution 2 mg Subcutaneous Gilead Sciences Ireland Uc 2020-12-16 Not applicable EU 
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
- 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]
- Kang C, Syed YY: Bulevirtide: First Approval. Drugs. 2020 Oct;80(15):1601-1605. doi: 10.1007/s40265-020-01400-1. [Article]
- 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]
- 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]
- EMA Public Assessment Report: Hepcludex (bulevirtide) powder for injectable solution [Link]
- 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]
- Fierce Biotech: Gilead snaps ups German virology biotech MYR, nabbing a European-approved hepatitis D therapy [Link]
- 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]
- NIH StatPearls: Hepatitis D [Link]
- Clinicaltrial.gov: Phase 2b Study of Bulevirtide (With Peginterferon Alfa-2a) in Patients With CHD [Link]
- MYR pharma: company page [Link]
- AP News: Gilead Sciences to Acquire MYR GmbH [Link]
- EMA Summary of Product Characteristics: Bulevirtide [Link]
- External Links
- Wikipedia
- Bulevirtide
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 3 Active Not Recruiting Treatment Chronic Hepatitis Delta 1 2 Completed Treatment Chronic Hepatitis Delta 1 2 Completed Treatment Chronic Viral Hepatitis B With Delta-agent 1 1 Recruiting Treatment Chronic Hepatitis D Infection 1 Not Available Completed Not Available Hepatitis D 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection, powder, for solution Subcutaneous 2 mg Injection, powder, for solution Subcutaneous 2 MG/vial - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
- Not Available
Targets
- 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
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
- EMA Public Assessment Report: Hepcludex (bulevirtide) powder for injectable solution [Link]
Drug created at May 20, 2019 15:04 / Updated at May 04, 2023 06:06