Gilead Announces New Interim Data from Phase 2b and Phase 3 Trials of Hepcludex (Bulevirtide), a First-in-Class Viral Entry Inhibitor for Chronic Hepatitis D

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Recently, Gilead Sciences announced the interim results from Phase 2b and Phase 3 clinical trials evaluating the antiviral drug Hepcludex (bulevirtide) for the treatment of chronic hepatitis D (HDV) infection. The Phase 3 study results supported the safety and efficacy of a once-daily 2 mg dose of bulevirtide. The Phase 2b study results demonstrated that 24 weeks of treatment with bulevirtide as monotherapy or in combination with pegylated interferon alfa-2a led to a significant reduction in HDV RNA levels and improved biochemical disease activity.

This drug is a first-in-class viral entry inhibitor developed for the treatment of chronic hepatitis B virus (HBV) and hepatitis D virus (HDV) infections. It inhibits NTCP, the HBV/HDV receptor on the surface of hepatocytes, and prevents the infection of regenerating cells and intrahepatic viral spread.

Phase 3 data will be included in the bulevirtide application to be submitted to the U.S. FDA later this year. In the United States, bulevirtide has previously been granted Breakthrough Therapy Designation (BTD) and Orphan Drug Designation (ODD) by the FDA. In Europe, Hepcludex has received conditional marketing authorization from the European Commission (EC) and PRIority MEdicines (PRIME) designation from the European Medicines Agency (EMA), making it the first drug approved in Europe for the treatment of chronic hepatitis D virus (HDV) infection and compensated liver disease in adults. It should be noted that in the EU, the EC has granted conditional marketing authorization specifically for the 2 mg dose of Hepcludex; all other doses and combinations remain investigational.

Interim results from the Phase 3 MYR301 study indicate that after 24 weeks of treatment, 36.7% and 28% of HDV patients in the bulevirtide 2 mg and 10 mg groups, respectively, achieved a combined virologic and biochemical response, compared with 0% in HDV patients who were observed and received no antiviral treatment. The 24-week efficacy of the bulevirtide 2 mg and 10 mg groups was superior to that of the untreated group (p < 0.001), with the 2 mg group demonstrating a numerically higher response rate compared to the 10 mg group.

Furthermore, compared with the bulevirtide 10 mg or untreated groups, more than 50% of patients in the bulevirtide 2 mg group experienced a rapid reduction in ALT levels to within the normal range. These results further reinforce the efficacy of bulevirtide in the treatment of HDV. Based on these interim results, the safety profile of bulevirtide during the 24-week treatment period was consistent with previous reports, with no bulevirtide-related serious adverse events (AEs), symptomatic elevations in bile salts, or AEs leading to treatment discontinuation reported.

The Phase 2b MYR204 study evaluated the safety and efficacy of bulevirtide monotherapy or in combination with peginterferon alfa-2a in patients with HDV. The study enrolled 175 patients with chronic HDV, who were randomized into 4 groups: peginterferon alfa-2a, bulevirtide + peginterferon alfa-2a, bulevirtide 10 mg + peginterferon alfa-2a, and bulevirtide 10 mg.

The results showed that after 24 weeks of treatment, a higher proportion of patients receiving bulevirtide achieved a combined response, with the highest response rate observed in the bulevirtide monotherapy group. Bulevirtide monotherapy or combination therapy with pegylated interferon alfa-2a was well tolerated, with adverse events being predominantly mild or moderate in severity. No serious adverse events or adverse events leading to discontinuation of bulevirtide were reported.

HDV is the most severe form of chronic viral hepatitis and is associated with the rapid progression of severe complications, including fibrosis, cirrhosis, and hepatocellular carcinoma. Currently, treatment options for HDV are highly limited, and patients generally have a poor prognosis, with a 5-year mortality rate of up to 50% among those with cirrhosis. HDV occurs exclusively as a co-infection in individuals infected with hepatitis B virus (HBV). It is estimated that at least 12 million people worldwide are currently co-infected with HDV and HBV. HDV infection can accelerate hepatic fibrosis, cirrhosis, and hepatic decompensation, thereby increasing the risk of hepatocellular carcinoma and mortality. Approximately 230,000 individuals in the United States and Europe are infected with HDV; however, globally, the disease remains significantly underdiagnosed.

Data from the aforementioned Phase 2b and Phase 3 studies add to the growing body of evidence supporting the potential role of bulevirtide in the treatment of HDV. Hepcludex (bulevirtide) represents the most clinically advanced novel therapy for HDV. Data from two Phase 2 studies (MYR202 and MYR203) that supported the EU marketing authorization demonstrate that treatment with Hepcludex significantly reduced viremia and improved liver function in HDV patients, with a favorable safety and tolerability profile.

Reference: Treatment With Hepcludex^® (Bulevirtide) Was Shown to Achieve Significant Response in Chronic Hepatitis Delta Virus After 24 Weeks