Bulevirtide: How a Peptide Entry Blocker Fights the World's Worst Hepatitis Virus
The peptide drug bulevirtide reduced hepatitis D virus levels in up to 77% of patients at its highest dose, establishing it as the first targeted therapy for this severe liver infection.
Quick Facts
What This Study Found
Bulevirtide, a first-in-class peptide entry inhibitor, significantly reduced hepatitis D virus (HDV) RNA levels when combined with tenofovir over 24 weeks. At the primary endpoint, 54% of patients on 2 mg bulevirtide, 50% on 5 mg, and 77% on 10 mg achieved either undetectable HDV RNA or a ≥2 log decline, compared to only 3% on tenofovir alone.
The 10 mg dose showed the strongest antiviral activity with a median 2.03 log10 decline in HDV RNA. However, HDV RNA rebounded after stopping bulevirtide, indicating the need for longer treatment. The drug was generally well tolerated, with asymptomatic bile salt increases being the most common side effect. No treatment-related deaths occurred.
Key Numbers
n=120 · 3 dose groups + control · 10 mg: 77% response · 2 mg: 54% response · TDF alone: 3% response · Median HDV RNA decline: 2.03 log10 (10 mg) · 24-week treatment
How They Did This
Multicentre, randomised, open-label, parallel-group Phase 2 trial (MYR202) across 16 hospitals in Germany and Russia. 120 adults with chronic hepatitis D (including 59 with cirrhosis) were randomized 1:1:1:1 to receive bulevirtide at 2 mg, 5 mg, or 10 mg subcutaneously daily plus oral tenofovir, or tenofovir alone, for 24 weeks. HDV RNA was monitored through week 48.
Why This Research Matters
Hepatitis D is the most severe form of viral hepatitis, affecting an estimated 12–72 million people worldwide, and until bulevirtide there was no approved targeted therapy. This trial provided key Phase 2 evidence supporting the conditional European approval of bulevirtide — the first peptide-based viral entry inhibitor for any hepatitis virus. It represents a completely new therapeutic approach: blocking the virus from entering liver cells rather than targeting viral replication.
The Bigger Picture
Bulevirtide represents a paradigm shift in hepatitis D treatment — it's the first drug to block viral entry into liver cells rather than targeting replication. This trial was instrumental in bulevirtide receiving conditional approval in Europe in 2020, and ongoing studies are evaluating longer treatment durations and combination approaches that could potentially cure hepatitis D.
What This Study Doesn't Tell Us
Open-label design means neither patients nor doctors were blinded, which could introduce bias. The sample size of 120 patients is moderate for a Phase 2 trial. HDV RNA rebounded after treatment cessation, so durability of response with longer treatment is unknown. The study did not assess functional cure (HDV RNA clearance sustained off-treatment).
Questions This Raises
- ?Can longer treatment durations with bulevirtide achieve sustained viral clearance after stopping therapy?
- ?Would combining bulevirtide with pegylated interferon lead to higher functional cure rates?
- ?Could the entry-inhibitor approach used by bulevirtide be adapted for other hepatitis viruses?
Trust & Context
- Key Stat:
- 77% response rate at 10 mg dose Bulevirtide achieved a ≥2 log decline or undetectable HDV RNA in 77% of patients at the highest dose, versus just 3% with standard antiviral therapy alone.
- Evidence Grade:
- This is a Phase 2 randomized controlled trial published in The Lancet Infectious Diseases with 120 patients. While the open-label design is a limitation, the randomization, clear dose-response relationship, and large effect size versus control provide moderately strong evidence.
- Study Age:
- Published in 2023 with data from a 2016 trial. Bulevirtide has since received conditional European approval and continues in Phase 3 studies. The findings remain highly relevant to current hepatitis D treatment.
- Original Title:
- Safety and efficacy of bulevirtide in combination with tenofovir disoproxil fumarate in patients with hepatitis B virus and hepatitis D virus coinfection (MYR202): a multicentre, randomised, parallel-group, open-label, phase 2 trial.
- Published In:
- The Lancet. Infectious diseases, 23(1), 117-129 (2023)
- Authors:
- Wedemeyer, Heiner(2), Schöneweis, Katrin, Bogomolov, Pavel, Blank, Antje, Voronkova, Natalia, Stepanova, Tatiana, Sagalova, Olga, Chulanov, Vladimir, Osipenko, Marina, Morozov, Viacheslav, Geyvandova, Natalia, Sleptsova, Snezhana, Bakulin, Igor G, Khaertynova, Ilsiyar, Rusanova, Marina, Pathil, Anita, Merle, Uta, Bremer, Birgit, Allweiss, Lena, Lempp, Florian A, Port, Kerstin, Haag, Mathias, Schwab, Matthias, Zur Wiesch, Julian Schulze, Cornberg, Markus, Haefeli, Walter E, Dandri, Maura, Alexandrov, Alexander, Urban, Stephan
- Database ID:
- RPEP-07538
Evidence Hierarchy
Participants are randomly assigned to treatment or placebo groups to test cause and effect.
What do these levels mean? →Frequently Asked Questions
What is bulevirtide and how does it treat hepatitis D?
Bulevirtide is a peptide drug that blocks hepatitis B and D viruses from entering liver cells. It's the first therapy specifically designed to target hepatitis D by acting as an entry inhibitor. In this trial, daily injections reduced virus levels in up to 77% of patients over 24 weeks.
Is bulevirtide a cure for hepatitis D?
Not yet — in this trial, virus levels rebounded after stopping treatment, suggesting ongoing therapy is needed. Researchers are now studying longer treatment durations and combination approaches that might achieve sustained viral clearance. Bulevirtide is conditionally approved in Europe under the brand name Hepcludex.
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Cite This Study
https://rethinkpeptides.com/research/RPEP-07538APA
Wedemeyer, Heiner; Schöneweis, Katrin; Bogomolov, Pavel; Blank, Antje; Voronkova, Natalia; Stepanova, Tatiana; Sagalova, Olga; Chulanov, Vladimir; Osipenko, Marina; Morozov, Viacheslav; Geyvandova, Natalia; Sleptsova, Snezhana; Bakulin, Igor G; Khaertynova, Ilsiyar; Rusanova, Marina; Pathil, Anita; Merle, Uta; Bremer, Birgit; Allweiss, Lena; Lempp, Florian A; Port, Kerstin; Haag, Mathias; Schwab, Matthias; Zur Wiesch, Julian Schulze; Cornberg, Markus; Haefeli, Walter E; Dandri, Maura; Alexandrov, Alexander; Urban, Stephan. (2023). Safety and efficacy of bulevirtide in combination with tenofovir disoproxil fumarate in patients with hepatitis B virus and hepatitis D virus coinfection (MYR202): a multicentre, randomised, parallel-group, open-label, phase 2 trial.. The Lancet. Infectious diseases, 23(1), 117-129. https://doi.org/10.1016/S1473-3099(22)00318-8
MLA
Wedemeyer, Heiner, et al. "Safety and efficacy of bulevirtide in combination with tenofovir disoproxil fumarate in patients with hepatitis B virus and hepatitis D virus coinfection (MYR202): a multicentre, randomised, parallel-group, open-label, phase 2 trial.." The Lancet. Infectious diseases, 2023. https://doi.org/10.1016/S1473-3099(22)00318-8
RethinkPeptides
RethinkPeptides Research Database. "Safety and efficacy of bulevirtide in combination with tenof..." RPEP-07538. Retrieved from https://rethinkpeptides.com/research/wedemeyer-2023-safety-and-efficacy-of
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Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.
This study breakdown was produced by the RethinkPeptides research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.