Hepatitis B: Is a Cure Possible?
With the momentum growing around hepatitis B drug discovery research, we are closer than ever to a cure.
From the Spring 2016 B Informed Newsletter
With the momentum growing around hepatitis B drug discovery research, how far are we from a cure?
Closer than ever, according to Timothy Block, PhD, president and co-founder of the Hepatitis B Foundation and its research arm, the Baruch S. Blumberg Institute. He points out that hepatitis C, initially thought to be incurable, can now be cured with new combination treatments.
“Hepatitis B is in a similar position,” Block believes. And the need for a cure has never been greater, with over 240 million people living with chronic hepatitis B infection worldwide, resulting in 1 million deaths per year from related liver failure and liver cancer.
“Treatments are available,” explains Block, “but we have become a little too comfortable with the seven medications that are currently approved for use.” While these drugs are effective, the interferons have many side effects and the oral antivirals require lifelong use. Moreover, they work in only about half of the infected population, and reduce the rate of death due to liver disease by only about 40 to 70 percent.
For those who benefit from treatment, the antiviral drugs prove that medications can be effective. However, there are millions who do not benefit and are still left vulnerable. “We should not accept that a significant number of people will still die from hepatitis B-related complications despite taking the current drugs,” Block declares.
What would a cure look like?
The current antiviral agents are similar and combinations do not offer any advantage. They have limited effectiveness against cccDNA, the seemingly indestructible “mini-chromosome” of the hepatitis B virus that continues to produce virus particles in infected liver cells, even in people being treated. A cure, therefore, would have to destroy or silence cccDNA and provide long-term protective immunity. Because one-drug treatments can lead to drug resistance, a cure would almost certainly involve combination therapy.
With the recent advances in hepatitis B research, scientists are optimistic that another big leap in the search for a cure is possible if other complementary drugs can be found.
The Baruch S. Blumberg Institute of the Hepatitis B Foundation is at the forefront of research efforts to discover such new drugs.
Blumberg Institute at the forefront
Blumberg scientists have played a key role in increasing understanding of the virus life cycle and are recognized leaders in drug discovery research that also includes designing and developing assays to screen for new drugs.
“With our Drexel University colleagues, we are among the first, if not the only group, to identify a small molecule that inhibits hepatitis B virus cccDNA formation,” Block notes. This is significant because inhibition of cccDNA is considered essential in achieving a complete cure. Block is confident that a drug with this mechanism will eventually become available.
In 2015, the Blumberg Institute licensed several of its discoveries to Arbutus Biopharma, the first company solely dedicated to hepatitis B drug discovery, and signed a three-year research agreement to work on novel approaches to developing a hepatitis B cure. “This unique partnership will allow us to move our discoveries more rapidly from the lab to the clinic,” Block explains.
Adding to its drug arsenal, Blumberg researchers have used computer modeling to design and produce targeted drugs against hepatitis B and liver cancer. In another innovative approach, researchers are screening plant and fungal extracts from its Natural Products Collection, donated by Merck & Co. in 2011, and have already discovered two potential drugs that are active against hepatitis B.
Getting close to the finish line
“There has never been more optimism than right now that a cure is within reach,” says Block. “This is the goal of the Hepatitis B Foundation, so we are all very excited.” Blumberg researchers are building on recent discoveries that have heightened the momentum around finding a cure for hepatitis B and liver cancer: new screening methods to search for effective drugs; new ways to treat hepatitis B using different approaches to shut down the virus; a new blood biomarker that aids in the early detection of liver cancer; and a promising drug that selectively kills liver cancer cells in animal studies.
“The years that we all have spent working towards a cure for hepatitis B have laid the groundwork for this final phase,” said Block.
“We are committing everything we have, every resource at our disposal, to developing the therapies that will ultimately improve the lives of all people living with hepatitis B worldwide and ultimately relegate hepatitis B to the history books.”
Baruch S. Blumberg Institute HBV Research Pipeline
The Baruch S. Blumberg Institute (BSBI) of the Hepatitis B Foundation is leading the charge in developing innovative new therapies against hepatitis B. Among the products in the pipeline:
We are among the first, if not the only group, to identify the first small molecule inhibitor of HBV cccDNA, which has now been made highly active and is licensed to Arbutus Biopharma for further development.
Capsid Inhibitors, “YES Kinase” Inhibitors
We are using high-throughput screens and computer modeling to design and produce targeted drugs that include capsid inhibitors for HBV and “YES kinase” inhibitors for liver cancer.
Immune System Activators
We have developed a new HBV drug that works by activating an infected liver cell’s own immune system, which has been shown to be effective in animal studies.
Natural Antiviral Agents
We have screened thousands of plant and fungal extracts from our extensive Natural Products Collection and identified two new leads that show potential activity against HBV.