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VIENNA -- Among patients with chronic hepatitis D virus (HDV), subcutaneous treatment with the investigational antiviral bulevirtide led to a combined response of an undetectable HDV RNA level and normalization of alanine aminotransferase (ALT) at 48 weeks, a phase III randomized trial showed.

In a group of 150 patients with or without compensated cirrhosis, this combined response occurred in 45% of those who received 2-mg bulevirtide, 48% of those who received 10-mg bulevirtide, and 2% of those in the control group (P<0.001 for the comparison of each treatment group with the control group), reported Heiner Wedemeyer, MD, of the University of Hannover in Germany, during the European Association for the Study of the Liver annual meeting.

At 48 weeks, the HDV RNA level was undetectable in 12% of patients in the 2-mg group and in 20% in the 10-mg group (P=0.41). Compared with 12% of patients in the control group, the ALT level normalized in 51% in the 2-mg group (difference from control, 39 percentage points, 95% CI 20-56), and 56% in the 10-mg group (difference 44 percentage points, 95% CI 26-60), according to the study, which was also published in the .

Loss of hepatitis B virus (HBV) surface antigen (HBsAg) or an HBsAg level that decreased by at least 1 log₁₀ IU/mL did not occur in the bulevirtide groups by 48 weeks.

HDV is a satellite RNA virus that requires HBsAg to enter into hepatocytes, and is estimated to affect 10 to 20 million people worldwide. Long-term coinfection with HBV and HDV is considered to be the most serious type of chronic viral hepatitis, the researchers noted.

While bulevirtide was recently approved in Europe for the treatment of HDV, the FDA rejected it in 2022, citing manufacturing and delivery concerns. The developer said it is still in with the agency, however.

During his presentation, Wedemeyer noted that treatment with bulevirtide for 96 weeks demonstrated improved combined response compared with week 48 (55% with 2 mg, 56% with 10 mg, and 39% for control group).

In an , Marc Ghany, MD, MHSc, of the National Institute of Diabetes and Digestive and Kidney Diseases, noted that HDV is known for its aggressive course.

"There is tantalizing evidence that long-term suppression of HDV viremia may lead to clinical improvement and cure," Ghany wrote. "A patient who received uninterrupted treatment with bulevirtide for 3 years had resolution of esophageal varices with histologic improvement and, more important, maintained undetectable viremia with normal ALT levels for 72 weeks after treatment -- findings that suggest the possibility of cure without HBsAg loss."

"Caution should be exercised when interpreting findings from this case report because spontaneous HDV clearance can occur," he added. "Nevertheless, the results of the trial by Wedemeyer and colleagues offer a glimmer of hope for an orphan disease, and the final results of the trial are eagerly awaited."

For this study, Wedemeyer and team randomly assigned 49 patients to the 2-mg bulevirtide group (mean age 44, 61% men, 84% white), 50 to the 10-mg group (mean age 41, 60% men, 86% white), and 51 to the control group (mean age 41, 51% men, 78% white). Most patients were still in the trial at 96 weeks.

Nearly half of each group had cirrhosis, and most had an HDV genotype of 1 and an HBV D genotype.

Serious adverse events occurred in all groups, but no events in the 2-mg and 10-mg groups were considered to be related to bulevirtide. Grade 3 adverse events considered to be related to bulevirtide occurred in one patient in the 2-mg group -- a decreased neutrophil count -- and in three patients in the 10-mg group, one event each of thrombocytopenia, neutropenia, and leukopenia. There were no grade 4 adverse events.

Headache, pruritus, fatigue, eosinophilia, injection-site reactions, upper abdominal pain, arthralgia, and asthenia were more common in the 2-mg and 10-mg groups compared with the control group.

The trial is ongoing and patients will be followed through week 168, Wedemeyer said.