Future Therapies for Functional Cure of Chronic HBV: Review of Investigational Drugs in Phase 1 and 2 Development

  • Lung-Yi Mak
  • Wai-Kay Seto
  • Man-Fung YuenEmail author
Hepatitis B (J Lim, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Hepatitis B


Purpose of Review

Treating patients with chronic hepatitis B (CHB) infection with long-term oral antiviral therapy or pegylated interferon is the current standard of care (SOC). However, functional cure, defined as sustained hepatitis B surface antigen (HBsAg) seroclearance that is associated with favorable clinical outcomes, is a rarely achieved treatment endpoint with the SOC.

Recent Findings

Remarkable advances in CHB therapy have been made in the recent years. This review was aimed to describe the different new treatment agents that are in the clinical phase of development. These include two main groups of agents that either target the viral replication cycle or enhance host immune control on the hepatitis B virus (HBV). The former group includes viral entry inhibitor, RNA gene silencers, core protein inhibitors, nucleic acid polymer, and monoclonal antibodies. The latter group includes toll-like receptor agonists, RIG-1/NOD2 agonist, therapeutic vaccines, and apoptosis inducer.


While some agents show promise in reduction of HBsAg levels and even HBsAg seroclearance, others are relatively modest in term of additional virological control effected by their different modes of action against HBV. These agents are in general well tolerated. Many upcoming new drugs against HBV are expected to enter phase II clinical trials. New challenge ahead would be the choice and duration of combination therapy to achieve a satisfactory rate of HBsAg seroclearance.


Chronic hepatitis B virus Antiviral therapy Functional cure Hepatitis B surface antigen 


Compliance with Ethical Standards

Conflict of Interest

Lung-Yi Mak declares no potential conflicts of interest.

Wai-Kay Seto reports research grant support, speaker’s fees, and advisory board member for Gilead Sciences and speaker’s fees and advisory board member for AbbVie.

Man-Fung Yuen reports grants from Gilead Sciences, AbbVie, SpringBank Pharmaceuticals, Arrowhead Pharmaceuticals, Fujirebio, Bristol Myers Squibb, MSD, and Assembly Biosciences.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of MedicineQueen Mary HospitalHigh WestHong Kong
  2. 2.Department of MedicineThe University of Hong KongPok Fu LamHong Kong
  3. 3.State Key Laboratory of Liver ResearchThe University of Hong KongPok Fu LamHong Kong

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