Forecasting Phase Iii Design
GSK has not yet revealed its Phase III design. Because this is new territory in hepatitis B, the Phase III design will likely provide a blueprint on how other future trials will be set out, Seto notes.
What is public is that GSK will investigate bepirovirsen as a monotherapy in the Phase III. Seto says the trial will likely use functional cure as the primary endpoint. GSK is likely to do so because it is associated with significantly reducing the risk of end-stage liver disease, paving the way to improved patient survival, Yuen explains.
With functional cure, there is an expectation that the asset should offer maintained HBsAg loss for at least 24 weeks after the treatment period, Lampertico notes. Additionally, as the first step to functional cure, the fields consensus is that there should be a 30% HBsAg reduction from baseline, Feld adds.
Usually, a two-arm Phase III trial would include up to 1,000 patients but, if GSK chooses to include additional comparator arms, several hundred more patients will be needed, Seto says. But Yuen notes the Phase III having a total of 400 subjects might be enough. Numbers will eventually depend on how the trial is powered.
Inhibitors Of Viral Antigens
- Entry inhibitors: they act by blocking the Na+-taurocholate co-transporting polypeptide receptor used by HBV to enter hepatocytes.
- RNA interference: they target viral RNAs to block antigen production. This class includes two different types of compounds:
- siRNA : they act in the cytoplasm by binding to complementary viral mRNAs and triggering their elimination.
- ASO : these modified antisense oligonucleotides target all HBV RNAs to induce the cleavage of HBV RNAs both in the nucleus and cytoplasm via RNase H1.
4.1. Entry Inhibitors
4.2. RNA Interference
4.2.1. Small Interfering RNAs
4.2.2. Antisense Oligonucleotide
4.3. Inhibitors of HBsAg Release
Its Great Weve Got But Its Not Where We Need To Be He Says One Class Is Hard To Take The Other You Need To Take Forever
HBVs assault on the liver causes a disease called Hepatitis B . Most adults with hepB recover within one to three months after symptoms start, but when the infection persists longer than six months its considered chronic. As the virus attacks the liver cells, it leaves behind nasty scars called fibrosis. In up to one-third of the patients the scars become severe , eventually resulting in liver failure or liver cancer. While hepB can be fatal, it is treatable, but it is also easily prevented to a degree of 95% through routine, safe, immunisation.
Upscaling vaccination, screening and treatment is the best way to keep this viral criminal at bay. New developments or scientific breakthroughs in any of these three areas is bad news for HBV, but good news for us. So, when scientists on the frontline say this deadly disease is about to meet its match, its great news.
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The Latest In The Hepatitis B Drug Pipeline
Why cost and treatment length are some of the biggest concerns for drug manufacturers.
According to the Hepatitis B Foundation, hepatitis B is the most common serious liver infection in the world, with over 292 million people living with a chronic infection. Though incidence is lower in the United States, up to 80,000 Americans will still become newly infected with hepatitis B each year and more than 2 million Americans are chronically infected. While many people infected with hepatitis B virus may clear the virus in the acute phase , some people are unable to clear the virus and it progresses to chronic hepatitis B.
Treatment with one of the seven FDA approved antivirals, intended to reduce liver damage and extend patient survival, may require lifelong medication therapy, says H. Kelley Riley, MD, chief medical officer, EnvisionRxOptions, a pharmacy benefits and services company headquartered in Twinsburg, Ohio. Current antiviral therapy may be near $1,000 per month, therefore prevention strategies provide an effective way to significantly reduce spending.
Cost and cures
Cost and cures are at the forefront of needs for new hepatitis B treatments.
JNJ-3989 is a third-generation subcutaneously administered RNA interference therapy in phase 1/2 studies as a curative treatment for patients with chronic HBV.
Nucleoside Analogues Or Oral Antivirals
Antivirals, or NAs, slow down or stop the hepatitis B virus from reproducing, decreasing the risk of liver damage. Less liver damage occurs when there is less virus present.
People take NAs orally as a pill and experience very few side effects.
First-line treatments, such as Tenofovir disoproxil and entecavir, are potent and effective in suppressing the virus, but they only work for as long as a person takes them. Discontinuing treatment
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Antiviral Medication For Hepatitis B
Doctors may recommend antiviral medication for people with chronic hepatitis B, which occurs when the virus stays in your body for more than six months.
Antiviral medication prevents the virus from replicating, or creating copies of itself, and may prevent progressive liver damage. Currently available medications can treat hepatitis B with a low risk of serious side effects.
NYU Langone hepatologists and infectious disease specialists prescribe medication when they have determined that without treatment, the hepatitis B virus is very likely to damage the liver over time. People with chronic hepatitis B may need to take antiviral medication for the rest of their lives to prevent liver damage.
There are many different types of antiviral medications available, and your doctor recommends the right type for you based on your symptoms, your overall health, and the results of diagnostic tests. A doctor may take a wait-and-see approach with a person who has a healthy liver and whose blood tests indicate a low viral load, the number of copies of the hepatitis B virus in your bloodstream.
Someone with HIV infection or AIDS may have a weakened immune system and is therefore more likely to develop liver damage. The U.S. Centers for Disease Control and Prevention strongly recommends that people with HIV infection who are diagnosed with hepatitis B immediately begin treatment with antiviral medication.
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The Best Way To Cure Any Disease Is The One
Instead of the cure being a singular treatment or a singular element, like the kryptonite that threatens to destroy Superman, Dr Tavis says the cure to HBV will likely be a collection of powerful tools that together will have the strength to take on the virus.
Scientists all over the world are making huge advancements in new treatments that can attack the virus from every angle, he explains.
Like a squadron of disease-demolishing superheroes, some of the therapies in development focus on blocking the virus entering the cell in the first place, whilst others deactivate the DNA. There is one therapy that will distort the shell of the virus so HBV becomes inactive and unable to survive. Another will lock itself to the genetic material of the virus and either cause it to fall apart or stop it from working.
Clinical trials are underway to investigate how these various treatments can be combined to work safely and effectively with one another, so healthcare professionals will be able to pick from a toolbox of therapies to deliver patient-specific treatment. One pharmaceutical company, Replicor, is already doing it. Using a three-part combination of drugs, Replicor is achieving a functional cure rate of 35% in early clinical trials.
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How Common Is Hepatitis B
The number of people who get this disease is down, the CDC says. Rates have dropped from an average of 200,000 per year in the 1980s to around 20,000 in 2016. People between the ages of 20 and 49 are most likely to get it.
About 90% of infants and 25-50% of children between the ages of 1-5 will become chronically infected. In adults, approximately 95% will recover completely and will not go on to have a chronic infection.
As many as 1.2 million people in the U.S. are carriers of the virus.
European Commission And Thervacb Join Forces
The role of viral hepatitis as a public health threat has long been underestimated. Only very recently, the United Nations in their 2030 Agenda for Sustainable Development called for international action to combat viral hepatitis and reduce the disease burden. The major killer is the hepatitis B virus causing liver cirrhosis and liver cancer. Worldwide 880,000 humans die each year from the consequences of an HBV infection.
A prophylactic vaccine is available to prevent HBV infection, but more than 3% of the worlds population are chronically infected and do not profit from that vaccine anymore. For those suffering from chronic hepatitis B, until today no curative treatment option exists.
The European Commission therefore selected the project TherVacB led by Helmholtz Zentrum München for a five-year funding within the Horizon 2020 program. A consortium of leading virologists, immunologists and physicians specialized in treating viral hepatitis, will use a newly designed therapeutic vaccine, TherVacB, as an immunotherapy to cure HBV. TherVacB will be evaluated in a three-year clinical trial starting in 2022 conducted in Europe and in Africa. Integration of a partner site in Tanzania shall help building local capacities for diagnosing and treating hepatitis B and support an important goal of the consortium to raise awareness for hepatitis B.
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How Close Are We To Finding Hepatitis Bs Kryptonite
VaccinesWork spoke to virologist Dr John Tavis about an approaching arsenal of therapies.
As far as viral villains go, hepatitis B virus is among the most wanted. Claiming the lives of two people per minute, this ferocious disease has a hit rate on par with HIV/AIDS.
Seeping into the body through contact with the bodily fluids of an infected person, HBV latches onto cells in the liver, injects its DNA and hijacks the cells machinery to power its own replication. HBV is a silent assassin. It can hide out for decades, causing potentially life-threatening damage to the liver and spreading to new victims before any symptoms show claiming the lives of more than 800, 000 people each year.
New Immunotherapy ‘highly Effective’ Against Hepatitis B
- University College London
- Scientists have identified a new immunotherapy to combat the hepatitis B virus , the most common cause of liver cancer in the world.
Scientists at UCL have identified a new immunotherapy to combat the hepatitis B virus , the most common cause of liver cancer in the world.
Each year, globally, chronic HBV causes an estimated 880,000 deaths from liver cirrhosis and hepatocellular carcinoma/liver cancer .
The pioneering study used immune cells isolated directly from patient liver and tumour tissue, to show that targeting acyl-CoA:cholesterol acyltransferase , an enzyme that helps to manage cholesterol levels in cells*, was highly effective at boosting immune responses.
Published in Nature Communications, the findings show that blocking the activity of ACAT with ACAT inhibitors boosts the specific immune cells that can fight both the virus and associated cancerous tumours, demonstrating its effectiveness as an immunotherapy. Inhibiting ACAT was also found to impede HBV’s own replication, thereby also acting as a direct antiviral. ACAT inhibitors such as avasimibe, taken orally, have previously been shown to be well-tolerated as cholesterol-lowering drugs in humans.
Explaining the study, lead author Professor Mala Maini , said: “Chronic hepatitis B virus infection is a major global health problem and the most common cause of liver cancer in the world.
Grant funding came from the Wellcome Trust and Cancer Research UK.
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Is Hepatitis B Preventable
Chronic hepatitis B infection affects at least 250 million people worldwide, causing over 880,000 deaths annually. It is also the major cause of liver cancer, the second leading cause of cancer-related deaths in the United States.
Unlike its cousin hepatitis C, hepatitis B can be prevented with vaccines. If you are accidentally exposed to the virus, there are also drug therapies you can takeâcalled postexposure prophylaxisâto avert the infection.
Prognosis Improvement After Hbsag Clearance
These related studies provide clear recommendations that patients who achieve HBsAg clearance have favourable clinical outcomes compared to patients who achieve only HBV DNA suppression and HBeAg seroconversion. HBsAg clearance leads to biochemical, virological and liver histological improvements, and it significantly reduces the risk of HCC. However, HCC may occur after HBsAg seroclearance despite it being the ultimate treatment endpoint recommended by current guidelines. The risk factors associated with HCC include the presence of cirrhosis, male sex, and age50 years at the time of HBsAg clearance . Closer attention should be given to patients with one or more of these risk factors.
These high-risk patients should be re-examined in a timely manner even if HBsAg clearance is obtained. These results also suggest that achieving a functional cure early in the absence of cirrhosis results in a better prognosis .
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Maoto Suppresses Extracellular Hepatitis B Virus Production In Hepad387 Cells
To confirm the effect of maoto, we evaluated it in HepAD38.7 cells in more detail . We first confirmed that the maoto extract did not show any cytotoxicity at a concentration of 100 µg/ml . Then, the effect of maoto on HBV production was evaluated at various concentrations under 100 µg/ml . Consistent with the results in Figure 1C, maoto inhibited extracellular HBV production in HepAD38.7 cells in a dose-dependent manner . Maoto did not affect HBeAg production, which is thought to correlate with HBV pgRNA production, in the tested concentration range . These results confirmed the inhibitory effect of maoto on extracellular HBV production without any cytotoxicity and suggest that maoto inhibits a step in the HBV production process after HBV pgRNA expression.
Should All Patients With Chronic Hepatitis B Be On Treatment
Not all patients with chronic hepatitis B need to be on treatment. The decision to treat HBV is based on several factors including blood tests results, the patient’s age, and the risk of developing cirrhosis or liver cancer. Sometimes a liver biopsy is needed to see if there is significant liver damage to make a decision.
Hepatitis B medications are recommended for patients with detected HBV virus on a blood test and evidence of liver damage. Liver damage can be detected with a liver enzyme known as ALT. People with cirrhosis should be considered for treatment even if the liver enzymes appear normal.
Chronic hepatitis B may change over time. Patients can go through different phases with low amounts of virus and normal level of ALT followed by high viral loads and ALT levels. These bursts of virus activity usually don’t cause any symptoms but may cause liver damage overtime. It is important that people with chronic hepatitis B have blood tests on a regular basis to see if treatment is needed.
There are some medications which can cause hepatitis B “reactivation” which can lead to life threatening liver failure. These medications are used to treat some cancers, inflammatory conditions and hepatitis C. Reactivation reactions can be prevented and it is important to let your provider know you have HBV before you start any new medications.
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Fda Oks New Hepatitis B Drug
Drug Called Tyzeka Suppresses Hepatitis B Virus
Oct. 26, 2006 — The FDA yesterday approved a new drug, called Tyzeka, to treat chronic hepatitis B in adults.
In a large clinical trial, Tyzeka was shown to be an effective antiviral agent, capable of suppressing the hepatitis B virus and improving liver inflammation comparably to Epivir-HBV, one of five medications already approved to treat chronic hepatitis B. Tyzeka is not a cure, however.
The hepatitis B virus is spread when body fluid from an infected person enters the body of an uninfected person, sometimes by sexual contact or blood contamination.
“In a typical year, an estimated 70,000 Americans become infected with chronic HBV , and some 5,000 of them will die of the complications caused by the disease,” says Stephen Galson, MD, MPH, and director of the FDA’s Center for Drug Evaluation and Research.
“Tyzeka offers prescribers another option for treating these patients,” Galson continues in an FDA news release.
American Association For The Study Of Liver Diseases Recommendations
The 2016 AASLD guidelines for the treatment of chronic hepatitis B as well as select recommendations from the 2018 AASLD guidance update on the prevention, diagnosis, and treatment of chronic hepatitis B are outlined below and in the Guidelines section.
Adults with immune-active chronic hepatitis B infection
Administer antiviral therapy to lower the risk of morbidity and mortality associated with chronic hepatitis B infection.
The recommended initial agent for adults is PEG-IFN, entecavir, or tenofovir.
Adults with immune-tolerant chronic hepatitis B infection
Antiviral therapy is not recommended.
The AASLD suggests obtaining ALT levels at least every 6 months to monitor for potential transition to immune-active or -inactive chronic hepatitis B.
For select patients older than 40 years, the AASLD suggests antiviral therapy in the setting of normal ALT levels, elevated HBV DNA , and significant necroinflammation or fibrosis on liver biopsy specimens.
Adults with HBeAg-positive immune-active chronic hepatitis B who seroconvert to anti-HBe on nucleoside analog therapy
After a period of treatment consolidation , consider discontinuing NA therapy in noncirrhotic HBeAg-positive adults who seroconvert to anti-HBe while on NA treatment. If antiviral therapy is stopped, monitor the patient every 3 months for a minimum of 1 year for recurrent viremia, ALT flares, seroreversion, and clinical decompensation.
Adults with HBeAg-negative immune-active chronic HBV infection
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