Related Experiment Video
Updated: Aug 22, 2025
11:34
A Competent Hepatocyte Model Examining Hepatitis B Virus Entry through Sodium Taurocholate Cotransporting Polypeptide as a Therapeutic Target
Published on: May 10, 2022
2.3K
New hepatitis B drug development disillusions: time to reset?
1National Reference Center for Viral Hepatitis B, C, and D, Department of Virology, Hôpital Henri Mondor, Université Paris-Est, Créteil, France; Inserm U955, Créteil, France.
The Lancet. Gastroenterology & Hepatology
|November 7, 2022
Summary
New hepatitis B virus (HBV) drug development is stalled due to strict efficacy standards and unrealistic expectations for a rapid functional cure. Redefining clinical endpoints and development pathways is crucial for advancing HBV therapeutics.
Area of Science:
- Hepatology
- Virology
- Drug Development
Background:
- Hepatitis B virus (HBV) infection remains a significant global health challenge.
- Despite extensive research, the development of novel HBV therapeutics has stalled in recent years.
Purpose of the Study:
- To analyze the reasons behind the stalled development of new hepatitis B virus (HBV) drugs.
- To propose a revised framework for HBV drug development, focusing on achievable endpoints and realistic timelines.
Main Methods:
- Review of preclinical and clinical research limitations in HBV drug development.
- Analysis of current efficacy standards and approval criteria for HBV therapeutics.
- Examination of the heterogeneity of HBV infection and its impact on treatment.
Main Results:
- Key limitations include inappropriate clinical endpoints, overly stringent efficacy standards for functional cure, and mismatched expectations of drug mechanisms.
- Current drug classes in development are unlikely to achieve a functional cure within short treatment durations.
- HBV infection's heterogeneity complicates a one-size-fits-all treatment approach.
Conclusions:
- A new consensus among researchers, drug developers, and regulators is needed for clinically relevant and achievable endpoints.
- Redefining the objectives, timelines, and pathways for new HBV drug development is essential to overcome current stagnation.
- Achieving a functional cure for HBV requires a more pragmatic and adaptable development strategy.
Related Concept Videos
01:26Drug Discovery: Overview
8.3K
Drug discovery is a multifaceted process involving extensive screening, testing, and optimization of lead compounds to identify potential new drugs for therapeutic use. It combines several approaches, including screening large numbers of natural products, chemical modification of known active molecules, identification of new drug targets, and rational design based on biological mechanisms and drug-receptor structure. These approaches are carried out in both academic research laboratories and...
8.3K
01:07Physiological Pharmacokinetic Models: Incorporating Hepatic Transporter-Mediated Clearance
70
Drug transporters are critical in drug absorption, distribution, and excretion processes. They should be included in physiological-based pharmacokinetic (PBPK) models, which help predict human drug disposition. However, predicting this is challenging during drug development, especially when liver transport is involved. However, with a realistic representation of body transport processes, an accurate model may be possible.
A recent model describes pravastatin's hepatobiliary excretion,...
A recent model describes pravastatin's hepatobiliary excretion,...
70
01:14Hepatic Drug Clearance: Role of Transporters
93
In the liver and bile canaliculi, influx and efflux transporters modification can influence intrinsic clearance. Transporters play a significant role in moving drugs within liver cells. Elaborate models, such as the Biopharmaceutical Classification System (BCS), are essential to relate transporters to drug disposition. This system categorizes drugs into four classes based on solubility and permeability, providing insights into elimination routes and the effects of transporters following oral...
93
01:26Drug Administration and Therapy Phases: Overview
650
Drugs, the chemical agents used in diagnosing, treating, or preventing diseases, undergo a four-phase process of development: pharmaceutic, pharmacokinetics, pharmacodynamics, and therapeutic.
The pharmaceutical phase focuses on leveraging the physicochemical properties of the drug to design and manufacture an effective product. Variants include orally administered tablets or capsules, topical creams or ointments, and parenteral-delivery solutions or emulsions.
The pharmacokinetic phase...
The pharmaceutical phase focuses on leveraging the physicochemical properties of the drug to design and manufacture an effective product. Variants include orally administered tablets or capsules, topical creams or ointments, and parenteral-delivery solutions or emulsions.
The pharmacokinetic phase...
650
01:16Hepatic Drug Excretion: Influencing Factors
186
The biliary system of the liver, crucial for bile secretion and drug excretion, comprises intrahepatic bile ducts that merge to form the common hepatic duct. This duct, carrying hepatic bile, combines with the cystic duct, draining the gallbladder and forming the common bile duct, which empties into the duodenum. Bile, produced by hepatic cells lining the bile canaliculi, is composed primarily of water, bile salts, pigments, electrolytes, and lesser amounts of cholesterol and fatty acids. Bile...
186
01:29Microorganisms in Medicine and Therapeutics
184
Microorganisms play a fundamental role in vaccine development, gene therapy, and therapeutic production. Their biological properties are harnessed to advance medicine and public health. Beyond immunization, microorganisms contribute to gut health, antibiotic synthesis, and genetic disease treatment.Live Attenuated and Inactivated VaccinesLive attenuated vaccines, such as the measles, mumps, and rubella (MMR) vaccine, utilize weakened forms of pathogens to closely resemble natural infections.
184