If you are interested in the topic of drug development for a functional cure for HBV, in the scientific journal Viruses, researchers give you an interesting detailed reviews. The researchers introduced that the current goal of curing HBV is mainly functional cure, that is, to evaluate the decrease of hepatitis B surface antigen (HBsAg) level as the primary endpoint of chronic HBV infection.  

Characteristics of new hepatitis B drug development, participation at home and abroad is different, HBsAg disappears into a new target or endpoint 

Despite the availability of effective preventive vaccines and antiviral therapy over the past two to three decades, chronic HBV Infection remains a major health threat globally, being the leading cause of liver cirrhosis (LC) and hepatocellular carcinoma (HCC). Functional cure of HBV, defined as loss of HBsAg and undetectable serum HBV DNA, was associated with improved clinical outcomes in patients with chronic HBV infection.  

However, spontaneous HBsAg loss is rare, occurring in only 1% of all HBsAg-positive individuals per year, in addition, Currently available hepatitis B antiviral drugs can lead to lower functional cure rates, and patients receiving antiviral therapy every year the coefficient is less than 1%.

Nevertheless, researchers around the world are continuing their efforts to develop new drugs for chronic hepatitis B in the direction of HBsAg loss, which has become an antiviral New therapeutic targets or therapeutic endpoints.

Recently, global biopharmaceutical companies have attracted a lot of attention around the development of novel antiviral drugs, such as small interfering RNA (siRNA), Capsid assembly modulators (CAMs), nucleic acid polymers (NAPs), etc. These drugs can be combined with nucleoside (acid) analogs (NAs) or immunomodulatory therapy to achieve functional cure in a higher proportion of chronic hepatitis B subjects . In addition, the researchers point out that new assays are needed to improve the sensitivity of detecting very low levels of HBsAg and to identify the source of HBsAg production to measure the persistence of novel antiviral therapies in the direction of curing HBV.  

Cure for HBV is a key component of the global effort to eliminate viral hepatitis by 2030. Functional cure of chronic hepatitis requires disappearance of HBsAg, undetectable HBV DNA, and maintenance for at least 6 months after cessation. The disappearance of HBsAg is very rare, only 1% per year, even with the use of nucleoside drugs, the probability of HBsAg disappearance is even lower, less than 0.5% per year. To enable a higher proportion of functional cures (should be much higher than 1% in the past), new antiviral drugs, including NAPs, CAMs, siRNAs and ASOs, as well as novel immunomodulators such as Toll-like receptors (TLRs) are being developed Agonists, therapeutic vaccines and PD-1/PD-L1 inhibitors.     These drug candidates have shown promise in the direction of HBsAg disappearance in preclinical studies. Of course, these new drug candidates also have many unanswered questions, including the optimal drug combination, the optimal duration of treatment, the durability of achieving an immune response, and most critically, drug safety and tolerability. Nonetheless, researchers continue to see excitement and optimism about new drug development work in the field of HBV treatment, and it is expected that these drug candidates will make progress in many CHB subjects, specifically resulting in sustained HBsAg decline or functional cure.

Healthy Epilogue: This description, which focuses on a functional cure for HBV, was published on Viruses from two research institutions: Toronto, Canada Contributions by physicians from the Faculty of Medicine of the University and the Faculty of Medicine of the University of Ottawa. The researchers also proposed that the current detection technology for HBV surface antigen cannot distinguish between different subtypes of surface antigen and their sources, especially cccDNA and integrated HBV DNA.  

You may have questions, why sometimes the clinicians of the pilot hospitals are introducing the development of new chronic hepatitis B drugs, and sometimes Geely German, GlaxoSmithKline, ALG, Ascletis and other pharmaceutical companies are introducing the development of new chronic hepatitis B drugs. Because this is a job where you have me and I have you, and no one can do without! Without the discovery and development of compounds by biopharmaceutical companies, subsequent animal experiments and clinical trials cannot be carried out.

New drug development will involve many disciplines, such as early drug discovery work, which requires pharmaceutical chemistry, drug analysis, pharmacology and other pharmacy majors Technicians are mainly involved in the preclinical research of new drugs, that is, to develop the "drop of water" and "small pills", and then the research drugs will be available in subsequent clinical trials; At the beginning of drug development, a lot of market evaluations are to be done, including evaluating the safety and efficacy data of currently marketed drugs, whether new drugs are worth developing, and it is necessary to listen to the valuable opinions of clinicians. After all, clinicians are in direct contact with a certain drug. The front-line staff of the patients in the field, the drug candidates are ultimately developed for these patients, that is, clinical translation is the key. As a digression, the degree of participation in new drug development at home and abroad is quite different. Most of the domestic doctors are busy looking after patients. Compared with foreign countries, there are indeed too few clinicians who really focus on scientific research.

It is not an emergency. Many people who make appointments at Canadian hospitals at the beginning of the month will not be able to see a doctor until the end of the month, because many Canadian hospitals implement The most important thing is to see a doctor in the morning, and not to see a doctor in the afternoon and transfer to scientific research. Therefore, foreign doctors have the time and energy to invest in new drug development. This is not the case in the domestic situation. Medical workers work in the hospital in the morning and in the afternoon until they are on duty in the evening. Therefore, there are really few domestic ordinary doctors who are really involved in the research and development of new drugs. They are usually clinicians at the expert level of the pilot hospitals. It is to passively engage in scientific research for the purpose of evaluating professional titles, because time and energy are not allowed, and this kind of research is not considered a long-term scientific research work. In addition, the status of foreign pharmacists is higher than that of domestic pharmacists. To a large extent, they really undertake the guidance of rational drug use and safe drug use, which relieves the pressure on doctors.