Hepcludex Phase III data

In participants who sustained undetectability for one year after end of therapy, no relapses occurred in the second year of follow-up. In addition, sustained post-treatment undetectable HDV RNA was more frequent in participants with longer on-treatment HDV RNA undetectability at end of treatment: 90% (9/10) of those who had HDV RNA undetectability for ≥ 96 weeks at end of treatment remained HDV undetectable off-treatment. These new data, presented at the European Association for the Study of the Liver (EASL) Congress 2025, show the potential value of bulevirtide monotherapy for some adults living with chronic HDV, even after treatment has ended.

The findings (LBO-004) build on data, presented at The Liver Meeting 2024, hosted by the American Association for the Study of Liver Diseases (AASLD), from MYR301 which demonstrated a subset of participants treated with bulevirtide monotherapy had undetectable HDV RNA 48 weeks after stopping treatment. The presentation adds further insight by not only showing the durability of response post-treatment, but that sustained undetectability was more frequent in people with longer, on-treatment HDV RNA undetectability at the time of bulevirtide discontinuation. Furthermore, post-treatment hepatic serious adverse events (SAEs) were reported in 14% (20/142) of participants but were resolved in 85% (17/20) of these participants, most of whom restarted bulevirtide therapy.

MYR301 is a Phase III clinical trial (NCT03852719) evaluating the long-term efficacy and safety of bulevirtide in 150 people living with chronic HDV randomly allocated to treatment with bulevirtide 2 mg once daily (n=49), 10 mg once daily (n=50) or no antiviral treatment (delayed treatment, n=51). Primary efficacy and safety data was assessed at Week 48. After Week 48, participants in the delayed treatment group of the study were switched to bulevirtide 10 mg once daily for an additional 96 weeks. The total duration of treatment across all groups in the study is 144 weeks. The primary endpoint, combined response, is defined as an undetectable HDV RNA or ≥2log10 IU/ml decline from baseline and ALT normalization at Week 48. Secondary endpoints at Week 48 include undetectable HDV RNA (key secondary endpoint), ALT normalization, and a change from baseline in liver stiffness measured by transient elastography.

"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. “Previous results from MYR301 demonstrated the potential benefits of long-term treatment with bulevirtide. With this new data, we now have valuable insight into the durability of the response even after treatment has ended.”

"HDV is the most severe form of viral hepatitis with more rapid progression towards liver cancer and liver-related death. Previous data have demonstrated the potential of bulevirtide as a safe and effective treatment option and, as EASL and the European Medicines Agency guidelines recommend, continued treatment is encouraged as long as people are experiencing a clinical benefit,” said Professor Heiner Wedemeyer, Head and Chairman of the Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology at Hannover Medical School. “With the 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.”