Hepatitis B, a viral infection that affects the liver and can cause acute and chronic illness, affects approximately 296 million people worldwide, killing an estimated 820,000 people in 2019, according to the latest statistics from the World Health Organization (WHO). .
The virus is most commonly spread to children during childbirth, but can also be spread through contact with blood and other body fluids during sexual intercourse, unsafe injections, or contact with sharp instruments.
While acute hepatitis B infection usually resolves within six months and does not require treatment, chronic infection (i.e., infection that persists for more than six months) can become a lifelong problem, leading to serious long-term health problems, including liver damage, cirrhosis , and liver cancer. It can even be fatal.
“Chronic hepatitis B profoundly impacts patients’ quality of life. Physically, individuals may experience symptoms such as abdominal pain, fatigue, nausea, and vomiting. The psychological toll is equally severe, including fear of disclosure and dissemination. Experiences of discrimination and stigmatization can exacerbating social isolation, leading to depression and anxiety,” commented Sandra Phillips, senior scientist in the Liver Immunology Group at the Institute of Liver Diseases at King’s College London.
Therefore, a cure would significantly change patients’ lives and reduce the symptoms and psychological toll of chronic hepatitis B infection. But how close are we to curing the disease?
Searching for a ‘functional cure’ for hepatitis B
The ultimate goal, Phillips said, is to find a “functional cure” for hepatitis B, which can be defined as one that results in sustained undetectable levels of hepatitis B DNA and the disappearance of hepatitis B surface antigen (HBsAg) after treatment.
“This functional cure mimics the natural resolution of the infection, further reducing hepatocellular carcinoma (HCC) risk, making it a highly desirable outcome for patients. Due to the hepatitis B replication template, the cause of hepatitis B chronicity, covalent Complete cure and sterilization cure remain elusive due to the persistence of closed circular DNA (cccDNA) and the presence of integrated hepatitis B DNA fragments in the host chromosome,” explained Phillips.
Currently, the main options for patients with chronic hepatitis B include nucleoside/nucleotide analogue (NUC) antiviral treatments.
“Direct-acting antiviral drugs that target the viral polymerase that replicates the genome are the most common treatment options for chronic hepatitis B. They are well tolerated and effectively inhibit genome replication, but because the genome is not replicating even in the absence of Still exists, so a cure is difficult. It’s rarely achieved,” said Bill Schneider, a researcher at the Rockefeller University Laboratory of Virology and Infectious Diseases.
It’s important to note that there is also an established vaccine that provides protection against hepatitis B, but this is only a preventative measure and does not cure active infection.
Latest research on finding a cure for hepatitis B
However, there is a lot of research going on around finding treatments for hepatitis B, especially since its cousin virus, hepatitis C, can now be cured in about 95 percent of cases with antiviral drugs.
In fact, Schneider was recently involved in a study in which researchers developed a method to study hepatitis B in the laboratory to better understand the behavior and characteristics of the virus during key parts of its life cycle.
“Hepatitis B is considered a DNA virus, but its genome passes through RNA intermediates during replication. We exploited this feature by initiating hepatitis B genome replication with RNA. One benefit of this approach is that it has Excellent signal-to-noise properties, which allow us to identify and quantify rare drug-resistant variants in the population,” explains Schneider.
“Monitoring and addressing drug resistance is an important part of antiviral treatment development, so this approach may be useful in therapeutic efforts. “We also anticipate that this method could be used in early steps of drug discovery, such as high-throughput screening. ”
And, according to Phillips, the discovery of a cure for hepatitis C also appears to have spurred pharmaceutical and biotech companies, which are now redoubling their efforts to find a cure for hepatitis B.
Bepirovirsen enters Phase 3 development
Bepirovesan is a particularly promising treatment currently in development for the treatment of hepatitis B.
It is an investigational antisense drug designed to inhibit the production of viral proteins associated with hepatitis B. These proteins are associated with infection and replication, including hepatitis B surface antigen (HBsAg), which is also associated with poor prognosis in patients with chronic hepatitis B. Hepatitis B.
By simultaneously reducing HBV replication and suppressing viral antigens, it is hoped that this therapy will stimulate innate immunity and become a functional cure for patients.
The development of bepiprovirsen is the result of a collaboration between Ionis Pharmaceuticals and GSK, which licensed bepiprovirsen from Ionis in August 2019 under a collaborative development and licensing agreement.
The announcement earlier this year of the initiation of two randomized, double-blind, placebo-controlled Phase 3 trials to further evaluate bepirovesan marks an extremely positive step toward a cure for hepatitis B.
Vaccitech’s chronic hepatitis B treatment sees positive top-line data
Another drug that has so far shown positive results in clinical trials for the treatment of chronic hepatitis B infection is Vaccitech’s VTP-300; in March, positive final data from the drug’s Phase 1b/2a clinical trial were announced.
VTP-300 is a heterologous immunotherapy consisting of an initial dose using the company’s ChAdOx vector platform and a booster dose using MVA encoding multiple hepatitis B antigens, including full-length surface, modified polymerase and core antigens.
The trial itself included 55 patients with chronic hepatitis B and observed that VTP-300 significantly and sustainably reduced HBsAg in the patients.
In announcing the positive final data, Vaccitech Chief Executive Officer (CEO) Bill Enright said the company believes VTP-300 has the potential to be a “key component in a functional cure” for hepatitis B.
Challenges remain
As research continues, it does appear that a cure for this disease may be possible, but we are still in the early stages and there are many challenges to overcome before this can be achieved.
“Discovering a treatment will be a game-changer for everyone affected by this disease, potentially preventing millions of people from developing liver cancer.”
Sandra Phillips, Senior Scientist, Liver Immunology Group, Institute of Liver Diseases, King’s College London
Notably, finding a cure for hepatitis B has proven difficult due to the complexity of the hepatitis B replicative life cycle and the severe immune dysregulation present in chronic hepatitis B, Phillips said.
“It is becoming increasingly clear that combination therapies involving direct-acting antivirals (DAAs) and immunomodulators represent the future of hepatitis B treatment, each with a unique mode of action. However, it is established that functional The optimal combination of cure, appropriate timing and treatment duration is a major challenge. Most importantly, these treatment strategies must demonstrate an excellent safety profile,” said Phillips.
What is certain, however, is that ultimately developing a treatment for hepatitis B would be a “huge achievement,” given the toll chronic infection takes on a person’s life and the fact that it is clearly a major global health problem, Schneider said. Put it.
Phillips agrees: “Discovering a treatment would be a game-changer for everyone affected by this disease, potentially preventing millions of people from developing liver cancer.”
New technologies related to hepatitis B