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Digital ILC 2020: First-in-class entry inhibitor bulevirtide achieved sustained HDV RNA decline over 48 weeks as monotherapy and in combination with PEG-IFN-α in patients with HBV/HDV coinfection.

EUROPEAN ASSOCIATION FOR THE STUDY OF THE LIVER (EASL)

28 August 2020: Bulevirtide, a potential new treatment option for patients with HBV/HDV coinfection, has been proven to be safe and effective in a study focused on high-dose regimens presented today at The Digital International Liver Congress™ 2020. The first-in-class entry inhibitor treatment was assessed as both monotherapy and in combination with pegylated interferon alpha (PEG-IFNα), with continuous linear declines in HDV RNA observed during the 48-week treatment period.

HDV can potentially infect individuals with ongoing HBV infection and is estimated to affect 5% of the HBV-infected population, between 15–20 million people worldwide.1 Chronic HDV is considered to be one of the most aggressive types of viral hepatitis, and is associated with elevated risk of cirrhosis, liver decompensation, and hepatocellular carcinoma.2 Currently, the only recommended treatment option is PEG-IFNα,3 though its reported ability to maintain HDV suppression varies considerably.4 Bulevirtide is the first in a novel class of drugs which exploits the dependence of HDV on HBV. By binding to sodium taurocholate cotransporting polypeptide (NTCP) on the hepatocyte surface and disrupting its interaction with the hepatitis B surface antigen (HBsAg), bulevirtide prevents the entry of both viruses.2 Bulevirtide has previously been shown to achieve high rates of viral suppression and to be well tolerated over 48 weeks in Phase 2 trials.5,6

In this safety and efficacy study, patients with chronic HBV/HDV coinfection were randomized to either subcutaneous (sc) bulevirtide 10 mg once daily and PEG-IFNα 180 µg once weekly (group E; n=15), or sc bulevirtide 5 mg twice daily with tenofovir disoproxil fumarate (TDF) to control underlying HBV infection (group F; n=15). Patients were treated for 48 weeks, followed by a treatment-free (group E) or TDF-only (group F) period of 24 weeks. 

By the end of treatment, serum HDV RNA levels had declined, with median reductions from baseline of -6.09 log10 IU/mL and -4.58 log10 IU/mL, and were undetectable in 86.7% and 40.0% of patients in arms E and F, respectively. Levels of alanine aminotransferase (ALT), an indicator of liver damage, also declined, with 26.7% and 40% of patients achieving ALT normalization after 48 weeks, respectively. Furthermore, HBsAg became undetectable in one patient in arm E, suggesting ‘functional cure’. Overall, 143 treatment-related AEs were reported, but none were considered serious.

“These data demonstrate that high-dose administration of bulevirtide co-administered with PEG-IFNα or TDF for 48 weeks was safe and well tolerated in patients with HBV/HDV coinfection. Continuous HDV RNA decline can be achieved with bulevirtide monotherapy, and strong synergy with PEG-IFNα against HDV was observed”, explained Professor Heiner Wedemeyer of Hannover Medical School in Germany, who led the study. “This trial offers new treatment options for the most severe form of viral hepatitis”

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About The International Liver Congress™ 

This annual congress is the biggest event in the EASL calendar, attracting scientific and medical experts from around the world to learn about the latest in liver research. Attending specialists present, share, debate, and conclude on the latest science and research in hepatology, working to enhance the treatment and management of liver disease in clinical practice. This year, the congress is being held entirely digitally due to the global health situation. The Digital International Liver Congress™ 2020 will take place from 27–29 August 2020. For more information on attendance and registration, please visit https://ilc-congress.eu/.

About The European Association for the Study of the Liver (EASL) 

Since its foundation in 1966, this not-for-profit organization has grown to over 4,500 members from all over the world, including many of the leading hepatologists in Europe and beyond. EASL is the leading liver association in Europe, having evolved into a major European association with international influence, and with an impressive track record in promoting research in liver disease, supporting wider education, and promoting changes in European liver policy.

Contact 

For more information or to speak to an expert, please contact Sean Deans in the ILC Press Office at: 

Session details

Session title: Hepatitis B and D – Drug development
Date and time of session: Friday 28 August 2020, 12.15–12.30
Presenter: Heiner Wedemeyer
Abstract: 48 weeks of high dose (10mg) bulevirtide as monotherapy or with peginterferon alfa-2a in patients with chronic HBV/HDV co-infection

Author disclosures 

Heiner Wedemeyer has received honoraria for consulting or speaking, and/or research grants (last 5 years) from Abbott, AbbVie, Altimmune, BMS, Boehringer Ingelheim, Eiger, Falk, Gilead, JJ/Janssen-Cilag, Merck/Schering-Plough, Myr GmbH, Norgine, Novartis, Roche, Roche Diagnostics, and Siemens. 

References

  1. Noureddin M, Gish R. Hepatitis delta: epidemiology, diagnosis and management 36 years after discovery. Curr Gastroenterol Rep. 2014;16(1):365.
  2. Sureau C, Negro F. The hepatitis delta virus: replication and pathogenesis. J Hepatol. 2016;64(Suppl 1):S102–16.
  3. EASL. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol. 2017;67(2):370–98.
  4. Mentha N, et al. A review on hepatitis D: from virology to new therapies. J Adv Res. 2019;17:3–15.
  5. Wedemeyer H, et al. Final results of a multicenter, open-label phase 2b clinical trial to assess safety and efficacy of Myrcludex B in combination with tenofovir in patients with chronic HBV/HDV co-infection. J Hepatol. 2018;68(Suppl 1):S3.
  6. Wedemeyer H, et al. Final results of a multicenter, open-label phase 2 clinical trial (MYR203) to assess safety and efficacy of myrcludex B in combination with PEG-interferon Alpha 2a in patients with chronic HBV/HDV co-infection. J Hepatol. 2019;70(Suppl 1):e81.
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