Study shows significant antiviral activity of the active ingredient bulevirtide for the treatment of chronic hepatitis D virus infection

Between 10 and 20 million people worldwide are infected with the hepatitis D virus (HDV). An HDV infection is always associated with a hepatitis B virus infection. For this most severe form of chronic viral hepatitis, there has been no satisfactory therapeutic option to date. In a multicenter clinical phase II study, an international research team has now been able to show that the 24-week application of the active substance Bulevirtide, developed by DZIF virologist Prof. Stephan Urban at the Ruprecht-Karls University of Heidelberg, significantly reduced the hepatitis D viral load in the blood serum and liver of the test subjects. Treatment with the novel entry inhibitor is therefore a promising strategy for patients with chronic HDV infection and has been admitted to the EU since August 2020.

Of the approximately 250 million people chronically infected with the hepatitis B virus (HBV) worldwide, between 10 and 20 million are also infected with the hepatitis D virus (HDV). HDV uses HBV as a helper virus by packaging its RNA genetic material in HBV envelopes. This co-infection leads to the most severe form of viral liver disease. Unfortunately, the antiviral drugs currently available 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 come 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 evaluation of the study, published in the journal The Lancet Infectious Diseases, showed that application of the active ingredient Bulevirtide over 24 weeks significantly reduced the concentration of HDV RNA in the blood serum and liver of the test subjects and was well tolerated by the study participants. Although the concentration of hepatitis D virus RNA increased again in most patients after discontinuation of the medication, the study demonstrated very good response rates, but also indicates that longer-term treatment with bulevirtide is necessary. The efficacy in patients with already developed liver cirrhosis further demonstrates the safe applicability of Bulevirtide in patients 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.

"The study results are highly relevant for affected patients! The decisive factor is that not only were reduced hepatitis D virus levels observed, but in most cases the liver values improved significantly. Furthermore, the daily injections are no problem for those affected. The tolerability is really excellent," says Prof. Heiner Wedemeyer, Director of the Clinical Department of Gastroenterology, Hepatology and Endocrinology at Hannover Medical School, clinical director 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 the viral load and thus the efficacy of Bulevirtide not only serologically, but also in the liver, the site of viral replication," adds co-author Prof. Maura Dandri from the University Medical Center Hamburg-Eppendorf.

"The successful development of bulevirtide from basic research into clinical practice is of crucial importance for many patients for whom there was previously no treatment option," summarizes the last author of the study, Prof. Stephan Urban, DZIF Professor of Translational Virology and Head of the Hepatitis B Research Group at Ruprecht-Karls-Universität Heidelberg.