In patients chronically infected with hepatitis D virus and hepatitis B virus (HBV), the use of Bulevirtide in combination with Tenofovir disoproxil fumarate (TDF) was associated with a significant decrease in hepatitis D virus RNA over 24 weeks. In this multicenter, randomized, parallel-group, open-label, phase 2 study (MYR202), Heiner Wedemeyer et al. examined the antiviral effect of Bulevirtide in individuals with hepatitis D virus and HBV coinfection.

Adults aged 18 to 65 years of age with chronic hepatitis D virus infection, encompassing those with cirrhosis, who were ineligible for pegylated-interferon-α (PegIFNα) therapy, or for whom treatment was unsuccessful, were recruited. Subjects were randomized (1:1:1:1) to get either TDF alone orally (245 mg once daily; n=30) or TDF plus 2 mg (n=28), 5 mg (n=32), or 10 mg (n=30) Bulevirtide once a day subcutaneously for 24 weeks.

A digital block technique with stratification was used for randomization, with 480 randomization numbers divided into 30 blocks. The key outcome, evaluated in modified intention-to-treat population which included people who were given investigational medicine at least once post-randomization, was undetectable hepatitis D virus RNA or a 2 log10 IU/mL or greater drop in hepatitis D virus RNA at 24th week. Until week 48, hepatitis D virus RNA levels were monitored. All subjects who got Bulevirtide or TDF at least once had their safety evaluated.

Overall, 120 individuals (59 of whom had cirrhosis) were included after a total of 171 subjects with chronic hepatitis D virus infection were screened. At week 24, 15 (54%) of 28 subjects treated with 2 mg of Bulevirtide, 16 (50%) of 32 treated with 5 mg of Bulevirtide, and 23 (77%) of 30 treated with 10 mg of Bulevirtide attained undetectable hepatitis D virus RNA or a 2 log10 IU/mL or higher decrease in hepatitis D virus RNA when compared to 1 (4%) of 28 with TDF only.

Hepatitis D virus RNA levels were reported to rebound by 48th week (24 weeks following Bulevirtide termination), with the median alterations from week 24 to week 48 of 1.923 log10 IU/mL (IQR 0.566-2.485) with 2 mg of Bulevirtide, 1.732 log10 (0.469-2.568) with 5 mg of Bulevirtide, and 2.030 log10 (1.262-2.903) with 10 mg of Bulevirtide. No fatalities related to the therapy were witnessed. Serious side effects occurred in 9% (n = 3) patients receiving 5 mg Bulevirtide, 7% (n = 2) patients receiving 10 mg Bulevirtide, and 4% (n = 1) patient receiving TDF. Elevation in alanine aminotransferase, aspartate aminotransferase, and asymptomatic bile salt levels were common treatment-emergent adverse effects.

Thus, Bulevirtide, a first-in-class peptidic entry suppressor for HBV and hepatitis D virus infection, caused a significant decrease in hepatitis D viral RNA. However, hepatitis D virus RNA levels rebounded after Bulevirtide cessation.