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A fragment of the hepatitis B virus's own envelope protein, turned into a drug that locks the door the virus uses to enter the liver.
Also known as: Hepcludex · Myrcludex B · bulevirtide acetate
Part of the Foundational & therapeutic peptides cluster
Overview
Bulevirtide (Hepcludex) is a synthetic lipopeptide copied from the pre-S1 domain of the hepatitis B virus large envelope protein. It binds the sodium/bile-acid cotransporter NTCP on hepatocytes and blocks entry of hepatitis B and D viruses. Approved by the EMA in 2020, the UK in 2021 and the US FDA in May 2026 for chronic hepatitis D, it produced a combined virological and biochemical response in 45–48% of patients at 48 weeks versus 2% of untreated controls in the phase 3 MYR301 trial.
Source & context
Biological / chemical source: Synthetic lipopeptide derived from the pre-S1 domain of the hepatitis B virus large surface protein
Primary research or clinical context: Approved (EMA, 2020; UK, 2021; US FDA, May 2026) for chronic hepatitis D virus infection with compensated liver disease
What bulevirtide is
Bulevirtide is an antiviral lipopeptide whose sequence comes from the virus it fights. Hepatitis B virus enters liver cells by binding a bile-acid transporter, NTCP, through the pre-S1 domain of its large envelope protein; bulevirtide is a synthetic, lipidated copy of that domain, which occupies NTCP and blocks entry of both hepatitis B and hepatitis D viruses. Hepatitis D — a defective virus that needs HBV to replicate — causes the fastest-progressing form of viral hepatitis, and bulevirtide is its first approved specific treatment: EMA in 2020 (after orphan designation in 2015), the UK in 2021, and the US FDA in May 2026 (IUPHAR record; Kang & Syed, Drugs 2020).
How it works
NTCP (SLC10A1) normally shuttles bile acids into hepatocytes; HBV hijacks it as a receptor. By binding NTCP, bulevirtide functionally blocks viral entry, preventing infection of new hepatocytes while existing infected cells are cleared or die off. Because HDV depends on HBV's envelope to enter cells, blocking the HBV entry receptor stops HDV too. This is a mechanism of prevention of spread within the liver rather than direct inhibition of viral replication, which is why response builds over months and why combination with interferon has been studied (Asselah et al., NEJM 2024).
Why hepatitis D matters
Hepatitis D virus infection occurs only alongside hepatitis B and affects an estimated 12 to 72 million people worldwide. It drives more rapid progression to cirrhosis and higher rates of hepatocellular carcinoma than HBV alone or hepatitis C. Acute co-infection usually clears, but HDV superinfection of someone already carrying HBV typically becomes chronic (Negro & Lok, JAMA 2023). Before bulevirtide, off-label pegylated interferon was the only option recommended by guidelines.
MYR301: the phase 3 trial
MYR301 randomised 150 patients with chronic hepatitis D, with or without compensated cirrhosis, to subcutaneous bulevirtide 2 mg/day or 10 mg/day for 144 weeks, or to no treatment for 48 weeks followed by 10 mg/day. At week 48, the primary endpoint — undetectable HDV RNA or a ≥2 log10 decline, plus normalised ALT — was reached by 45% of the 2 mg group and 48% of the 10 mg group versus 2% of controls (P<0.001 for each). HDV RNA was undetectable in 12% and 20% respectively, and ALT normalised in 51% of the 2 mg group versus 12% of controls (Wedemeyer et al., NEJM 2023).
| Endpoint | Bulevirtide 2 mg/day | Bulevirtide 10 mg/day | Untreated control |
|---|---|---|---|
| Combined response (primary) | 45% | 48% | 2% |
| Undetectable HDV RNA | 12% | 20% | — |
| ALT normalisation | 51% | — | 12% |
Longer treatment and what happens after stopping
By week 96, 95% of patients remained in the study, responses were maintained or improved, and rates were similar between 2 mg and 10 mg; 43% of early non-responders and 82% of partial responders at week 24 achieved a virological response by week 96, and adverse events were mostly mild with no serious events related to the drug (Wedemeyer et al., Journal of Hepatology 2024). At the end of 144 weeks, virological response was 73–92% across groups and undetectable HDV RNA 29–52%; but 96 weeks after stopping, virological response had fallen to about 30–33% and undetectability to about 20%, and 14% of patients had post-treatment hepatic serious adverse events, most of which resolved (Wedemeyer et al., Journal of Hepatology 2026). Responses, in other words, largely depend on continued treatment.
Combination with interferon
A phase 2b trial compared peginterferon alfa-2a alone, bulevirtide 2 mg or 10 mg plus peginterferon for 48 weeks followed by bulevirtide alone for 48 weeks, and bulevirtide 10 mg alone for 96 weeks, with undetectable HDV RNA 24 weeks after treatment as the primary endpoint — testing whether a finite course could achieve durable clearance (Asselah et al., NEJM 2024). ClinicalTrials.gov also lists trials comparing bulevirtide with newer agents, including an antibody, brelovitug, and an expanded-access programme.
Status as of September 2026
Bulevirtide is an approved prescription medicine for chronic hepatitis D in the EU, UK and, since May 2026, the United States. Its approval history is documented by the IUPHAR record and the Drugs first-approval review; a 2026 formulary entry lists the US product as bulevirtide acetate-gmod. It is a supervised antiviral, and nothing on this page is guidance on its use.
Structure & chemistry
Molecular identity & reference confidence
Source-supported reference
Reference values are taken from the cited molecular record or curated profile. A database match is not independent laboratory verification; modifications, counter-ions, and formulations can change the measured mass.
- Molecular form
- Peptide derived from the pre-S1 domain of the HBV large surface protein (HBsAg), lipidated to anchor at the hepatocyte membrane (IUPHAR record)
- Species
- Not established by this molecular identity audit
- Termini (N / C)
- Not specified / Not specified
Average reference mass
Reference policy updated: 2026-10-05
- IUPHAR/BPS source snapshot · 2026-10-01
- PubChem molecular record · 2026-10-01
- Molecular formula
- C248H355N65O72
- Average reference mass
- ≈ 5,399
- Receptors
- No receptor — binds the sodium taurocholate co-transporting polypeptide (NTCP, SLC10A1) on hepatocytes, the entry receptor for HBV and HDV
- Backbone
- Peptide derived from the pre-S1 domain of the HBV large surface protein (HBsAg), lipidated to anchor at the hepatocyte membrane (IUPHAR record)
- Status
- Approved: EMA, 2020 (chronic HDV with compensated liver disease); UK MHRA, 2021; US FDA, May 2026
- PubChem CID: 134687648
- IUPHAR ligand: 12775
- CAS RN: 2012558-47-1
- UNII: WKM56H3TLB
Chemistry values: curated profile, PubChem, IUPHAR/BPS Guide to Pharmacology · fetched 2026-10-01.
Clinical development snapshot
ClinicalTrials.gov lists 25 registered studies with “Bulevirtide” as an intervention (snapshot 2026-10-01). A registry footprint is not evidence of efficacy or approval.
| NCT | Title | Phase | Status | Updated |
|---|---|---|---|---|
| NCT05718700 | Study of Bulevirtide in Participants With Chronic Hepatitis D Infection | — | terminated | 2026-09-18 |
| NCT07454837 | Study to Evaluate Switching to Brelovitug for the Treatment of CHD in Participants Receiving Bulevirtide | Phase 3 | recruiting | 2026-09-10 |
| NCT07200908 | A Trial Evaluating Brelovitug (BJT-778) vs Bulevirtide for the Treatment of Chronic Hepatitis Delta Infection | Phase 3 | recruiting | 2026-08-25 |
| NCT07128550 | A Study to Evaluate Tobevibart+Elebsiran in Participants With Chronic HDV Infection Not Virologically Suppress | Phase 3 | active not recruiting | 2026-07-13 |
| NCT06780579 | Expanded Access for Bulevirtide | — | approved for marketing | 2026-06-12 |
| NCT07491848 | Oral-Periodontal Evaluation and Assessment of Oral Fluid Biomarkers in Patients With Hepatitis B+D | — | recruiting | 2026-03-25 |
Bulevirtide — reconstitution calculator
Enter how much peptide is in the vial and how much diluent (e.g. bacteriostatic water) is added. The tool returns the resulting solution concentration — and, for any amount you type, the volume it corresponds to. This is educational arithmetic, not a dosing recommendation.
Reference form: Peptide derived from the pre-S1 domain of the HBV large surface protein (HBsAg), lipidated to anchor at the hepatocyte membrane (IUPHAR record)Average reference mass: 5,399 Da
Enter an amount to see the volume it corresponds to.
Educational concentration mathematics only. This tool does not recommend a dose, amount, or protocol, and nothing here is medical advice. Many peptides are not authorized by Health Canada for human use — see our reconstitution and bacteriostatic-water guides for context.
Change log
Dated observations from the data pipeline (registry flags, trial footprints, identifiers) and editorial reviews of this profile.
- IdentifiersCross-linked to IUPHAR ligand 12775 and PubChem CID 134687648.
- TrialsClinicalTrials.gov snapshot added: 25 registered studies, highest phase 3.
- EditorialProfile content reviewed and updated by the editorial team.
FAQ about Bulevirtide
What is Bulevirtide?+
Bulevirtide (Hepcludex) is a synthetic lipopeptide copied from the pre-S1 domain of the hepatitis B virus large envelope protein. It binds the sodium/bile-acid cotransporter NTCP on hepatocytes and blocks entry of hepatitis B and D viruses. Approved by the EMA in 2020, the UK in 2021 and the US FDA in May 2026 for chronic hepatitis D, it produced a combined virological and biochemical response in 45–48% of patients at 48 weeks versus 2% of untreated controls in the phase 3 MYR301 trial.
What Canadian product status is recorded for Bulevirtide?+
Canadian product status for Bulevirtide has not been verified in this profile. No verified record here does not mean no authorization exists. Status depends on the product, formulation and use; consult Health Canada's product records.
What is the typical length of Bulevirtide?+
Bulevirtide is not a classic amino-acid chain peptide in the same sense; see the profile for classification details.
What is bulevirtide?+
A synthetic lipopeptide copied from the hepatitis B virus pre-S1 envelope domain that blocks the NTCP entry receptor on liver cells. Sold as Hepcludex, it is the first approved treatment for chronic hepatitis D.
How does bulevirtide work?+
It binds NTCP, the bile-acid transporter HBV and HDV use to enter hepatocytes, preventing new infection of liver cells rather than directly stopping viral replication.
Is bulevirtide approved?+
Yes — EMA in 2020, UK in 2021 and US FDA in May 2026, for chronic hepatitis D with compensated liver disease.
How effective is bulevirtide?+
In MYR301, 45–48% of patients reached the combined virological and biochemical response at 48 weeks versus 2% of untreated controls; responses fell substantially after treatment stopped.
Does the dose matter?+
In MYR301, 2 mg/day and 10 mg/day produced similar combined response rates at 48 and 96 weeks; undetectable HDV RNA was somewhat more frequent at 10 mg.
Related peptides
References & further reading
- 1.Wedemeyer H et al. (2023). A Phase 3, Randomized Trial of Bulevirtide in Chronic Hepatitis D. New England Journal of Medicine
- 2.Wedemeyer H et al. (2024). Bulevirtide monotherapy in patients with chronic HDV: Efficacy and safety results through week 96. Journal of Hepatology
- 3.Wedemeyer H et al. (2026). 144 Weeks of bulevirtide monotherapy for chronic hepatitis D: Final and post-treatment results. Journal of Hepatology
- 4.Asselah T et al. (2024). Bulevirtide Combined with Pegylated Interferon for Chronic Hepatitis D. New England Journal of Medicine
- 5.Negro F & Lok AS (2023). Hepatitis D: A Review. JAMA
- 6.Kang C & Syed YY (2020). Bulevirtide: First Approval. Drugs
- 7.PubChem — Bulevirtide (CID 134687648)