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| Primary information |
|---|
| ID | 16293 |
| Therapeutic ID | Th1803 |
| Protein Name | Bulevirtide |
| Sequence | NA
|
| Molecular Weight | NA |
| Chemical Formula | NA |
| Isoelectric Point | NA |
| Hydrophobicity | NA |
| Melting point | NA |
| Half-life | The half-life of bulevirtide ranges between 4 and 7 hours in healthy adults.[L30290] |
| Description | 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.[A226340,L30235] Until recently, there have been extremely limited treatments available for Hepatitis D infection.[A226305] 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.[L30215] In the USA, bulevirtide has been granted Orphan Drug Designation and Breakthrough Therapy Designation.[L30260,L30275] 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.[L30240] |
| Indication/Disease | Bulevirtide is indicated for the treatment of chronic Hepatitis D infection in HDV-RNA positive adult patients with compensated liver disease.[L30215] |
| 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.[L30215,L30220,L30260] |
| 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.[L30260] 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.[L30260] |
| Toxicity | There are no reports of overdose with bulevirtide. In the case of an overdose, monitor the patient and provide supportive treatment.[L30290] |
| 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.[L30215,L30290] |
| 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.[L30215] The estimated bioavailability is 85% in humans, and steady-state concentrations are expected to occur within weeks of initiating treatment.[A226375,L30290] 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.[L30215] |
| The volume of distribution of bulevirtide is estimated to be lower than total body water.[L30290] In animals, bulevirtide distributes into the liver, gastrointestinal tract, kidney, and bladder.[L30215] |
| 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.[L30215] The clearance of bulevirtide decreases as the dose increases.[L30290] |
| Categories | NA |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Sodium/bile acid cotransporter |
| Brand Name | Hepcludex |
| Company | Gilead Sciences Ireland Uc |
| Brand Description | Gilead Sciences Ireland Uc |
| Prescribed For | Subcutaneous |
| Chemical Name | 2 mg |
| Formulation | NA |
| Physical Appearance | The most common side effects with Hepcludex are raised levels of bile salts in the blood (which may affect more than 1 in 10 people) and reactions at the site of injection (which may affect up to 1 in 10 people). The most common serious side effect is worsening of liver disease after stopping Hepcludex (which may affect up to 1 in 10 people). |
| Route of Administration | Hepcludex is an antiviral medicine used to treat chronic (long-term) hepatitis delta virus (HDV) infection in adults with compensated liver disease (when the liver is damaged but is still able to work), when the presence of viral RNA (genetic material) has been confirmed by blood tests. |
| Recommended Dosage | N.Achronic (long-term) hepatitis delta virus (HDV) infection |
| Contraindication | NA |
| Side Effects | https://www.ema.europa.eu/en/medicines/human/EPAR/hepcludex |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |