Worldwide, 10 to 20 million people are infected with the hepatitis D virus (HDV). HDV infection is always associated with hepatitis B virus infection. For this most severe form of chronic viral hepatitis, there has been no satisfactory therapeutic option. In a multicenter phase II clinical trial, an international research team has now shown that the 24-week application of the compound Bulevirtide, developed by DZIF virologist Prof. Stephan Urban, significantly reduced the hepatitis D viral load in blood serum and liver. The novel entry inhibitor therefore represents a promising strategy in the treatment of chronic HDV infection.
Of the approximately 250 million people worldwide chronically infected with hepatitis B virus (HBV), between 10 and 20 million are also infected with hepatitis D virus (HDV). HDV uses HBV as a helper virus by packaging its RNA genetic material into HBV envelopes. This co-infection leads to the most severe course of viral liver disease. Unfortunately, the antiviral drugs available to date for the treatment of HBV-infected patients can only be used effectively in a small proportion of HDV patients and also cause side effects. With the development of Bulevirtide – an active ingredient conditionally approved in the EU since 2020 that blocks the entry of hepatitis B and hepatitis D viruses into liver cells – the goal of successfully treating hepatitis D has moved much closer.
The antiviral activity of Bulevirtide was tested in a multicenter phase II study in a total of 120 HBV/HDV-positive patients, 59 of whom had already developed liver cirrhosis. The analysis of the study, published in the journal The Lancet Infectious Diseases, showed that application of the active substance Bulevirtide for 24 weeks significantly reduced the concentration of HDV RNA in the blood serum and liver of the subjects and was well tolerated by the study participants. Although hepatitis D virus RNA levels increased again in most patients after discontinuation of medication, the study demonstrates very good response rates but also suggests that longer-term treatment with bulevirtide is needed. Efficacy in patients with previously developed cirrhosis continues to demonstrate the safe applicability of bulevirtide in sufferers with advanced liver disease, although no patients with decompensated cirrhosis – end-stage liver disease – were treated. Whether long-term treatment can also lead to a permanent reduction in viral load or even a complete loss of the virus is being investigated in ongoing further studies.
“For affected patients, the study results are of great relevance! Crucially, not only were reduced hepatitis D virus levels observed, but in most cases liver values improved significantly. Furthermore, the daily injections are not a problem for those affected in their daily lives. The tolerability is really excellent,” says DZIF scientist Prof. Heiner Wedemeyer, Director of the Department of Gastroenterology, Hepatology and Endocrinology at Hannover Medical School, clinical lead investigator of the phase II and III studies on Bulevirtide and first author of the publication.
“Due to the availability of liver biopsies, this study offers unique opportunities to investigate viral load and thus the effectiveness of bulevirtide not only serologically but also in the liver, the site of viral replication,” added co-author and DZIF scientist Prof. Maura Dandri from the University Medical Center Hamburg-Eppendorf.
“The successful development of bulevirtide from basic research into clinical practice is of drastic importance for many patients for whom there has been no treatment option so far,” summarizes the study’s last author, Prof. Stephan Urban, DZIF Professor of Translational Virology and Head of the Hepatitis B Research Group at Ruprecht-Karls-University Heidelberg.
Original publication:
Safety and efficacy of bulevirtide in combination with tenofovir disoproxil fumarate in patients with hepatitis B virus and hepatitis D virus coinfection (MYR202): a multicentre, randomised, parallel-group, open-label, phase 2 trial: The Lancet Infectious Diseases, 2022, DOI: 10.1016/S1473-3099(22)00318-8.
