Gilead Sciences announced groundbreaking final results from its pivotal Phase 3 MYR301 study showing that bulevirtide, a first-in-class entry inhibitor, provides lasting benefits for patients with chronic hepatitis delta virus (HDV) even after treatment discontinuation.
The data, presented at the European Association for the Study of the Liver (EASL) Congress 2025, revealed that 36% (23 out of 64) of adults with chronic HDV maintained virologic suppression for almost two years after stopping treatment with bulevirtide at either 2 mg or 10 mg doses.
Most significantly, the study found that patients who achieved longer periods of undetectable HDV RNA during treatment had better post-treatment outcomes. Among those who maintained undetectable HDV RNA for 96 weeks or more during treatment, 90% (9 out of 10) remained HDV-undetectable after stopping therapy.
"HDV is the most severe form of viral hepatitis with more rapid progression towards liver cancer and liver-related death," explained Professor Heiner Wedemeyer, Head and Chair of the Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology at Hannover Medical School. "With today's results, we're now seeing the potential of bulevirtide to maintain virologic suppression and normalize markers of liver inflammation for a subset of people living with HDV, demonstrating a durable response, even after treatment cessation."
Durability of Response
The new findings build on previous data presented at The Liver Meeting® 2024, which had shown that some participants maintained undetectable HDV RNA 48 weeks after stopping treatment. The latest results extend this observation period to nearly two years and provide critical insights into which patients are most likely to maintain a response.
Importantly, patients who sustained undetectability for one year after ending therapy experienced no relapses during the second year of follow-up, suggesting the possibility of a lasting response for some patients.
Safety data showed that post-treatment hepatic serious adverse events (SAEs) occurred in 14% (20/142) of participants but were resolved in 85% (17/20) of these cases, most after restarting bulevirtide therapy.
Clinical Significance
HDV infection represents the most severe form of viral hepatitis, affecting an estimated 4.5% of people living with chronic hepatitis B virus (HBV), with a global prevalence of approximately 12 million people. The virus causes accelerated progression to liver cirrhosis, hepatocellular carcinoma, and liver-related mortality compared to HBV infection alone.
"At Gilead, we are committed to advancing research and exploring the full potential of bulevirtide as a monotherapy, in combination, and at different doses, to help improve outcomes for people living with chronic HDV," said Anu Osinusi, Vice President, Clinical Research for Hepatitis, Respiratory and Emerging Viruses at Gilead. "With this new data, we now have valuable insight into the durability of the response even after treatment has ended."
Treatment Availability
Bulevirtide 2 mg (marketed as Hepcludex®) remains the only approved treatment for adults with chronic HDV and compensated liver disease in the European Economic Area, the UK, Switzerland, and Australia. The European Commission granted full Marketing Authorization in July 2023, upgrading from the conditional approval initially granted in July 2020.
The drug is not yet approved in the United States or other regions, where it remains an investigational product. The higher 10 mg dose used in the study is still investigational and not approved anywhere globally.
Study Design and Endpoints
The MYR301 trial evaluated bulevirtide in 150 people with chronic HDV, randomly allocated to receive bulevirtide 2 mg once daily (n=49), bulevirtide 10 mg once daily (n=50), or no antiviral treatment (delayed treatment, n=51). After Week 48, participants in the delayed treatment group were switched to bulevirtide 10 mg once daily for an additional 96 weeks, with a total treatment duration of 144 weeks across all groups.
The primary endpoint was a combined response, defined as undetectable HDV RNA or ≥2log10 IU/ml decline from baseline and ALT normalization at Week 48. Secondary endpoints included undetectable HDV RNA, ALT normalization, and changes in liver stiffness measured by transient elastography.
These findings represent a significant advancement in HDV treatment, potentially offering a subset of patients the possibility of maintaining viral suppression without indefinite therapy. For a disease that previously had no effective treatments, bulevirtide's durable post-treatment response marks a major milestone in hepatitis delta management.
