Baraclude (entecavir) offers much-needed new option for chronic hepatitis B infection

Baraclude (entecavir), a new oral drug developed by Bristol-Myers Squibb, recently approved by the European Commission for treatment of chronic hepatitis B viral (HBV) infections, is expected to become available in a few months in some countries of the EU, the Middle East and . It will provide a much-needed new antiviral therapy in the face of widespread resistance to existing therapies, according to liver specialists who discussed the drug during the 12^th International Symposium on Viral Hepatitis and Liver Disease held in , July 2006.

Alfredo Alberti, Associate Professor of Internal Medicine at , said. “Baraclude has a high response rate and is a highly selective and very potent inhibitor of hepatitis B with the ability to rapidly reduce viral load to undetectable levels in 89 to 90 per cent of people treated for 1 to 2 years.  These features will help prevent the emergence of resistance.”

Baraclude, which is 300 to 400 times more potent than other antivirals, is an option for first-line therapy and is the best candidate to be included in combination with other therapies, he added.

The drug is indicated for use in adults with chronic HBV infection with compensated liver disease and with evidence of active viral replication along with persistent elevations of aminotransferases.  Active liver disease determined by biopsy is also an indication.

Baraclude slows progression of chronic infection, said Professor Alberti.  Three Phase III clinical studies involving over 1600 patients worldwide have evaluated Baraclude in comaparison to lamivudine (the most commonly used oral antiviral therapy used to treat chronic hepatitis B worldwide) and have shown the drug has similar or superior efficacy. The trials included patients with compensated liver disease, naïve to prior antiviral therapy, resistant to lamivudine who are infected by either wild type virus (HbeAg positive) or with pre-core mutant virus (HbeAg negative).

After 48 weeks of treatment with Baraclude – or two years for those with only a virological response initially – patients achieved greater or similar responses in terms of liver inflammation suppression, extent of fibrosis, blood viral levels, normalisation of liver function and seroconversion compared to patients receiving lamivudine, he explained. The key primary efficacy endpoint at 48 and 96 weeks was improvement in liver histology with undetectable levels (<300 copies/ml) of the virus as the secondary endpoint. 

In addition to showing superior or similar efficacy compared to lamivudine, Baraclude also demonstrated a comparable safety profile, he noted.  In two of the trials, ETV-022 and ETV-027, 80 to 94 per cent of patients treated with Baraclude for up to 96 weeks achieved an undetectable viral load.

Professor Patrick Marcellin of the Viral Hepatitis Research Unit, Hopital Beaujon, , , said:  “Europe is likely to see a significant increase in prevalence and incidence of hepatitis B in the near future as high numbers of immigrants from countries where chronic hepatitis B is endemic, settle across .”  Two billion people are infected with hepatitis B worldwide of whom around 400 million are carriers of chronic disease.  An estimated one million people in are infected with hepatitis B each year of whom 90,000 become chronic carriers. Hepatitis B is the 10^th leading cause of death worldwide responsible for 1.2 million deaths annually.  It is also the leading cause of hepatocellular carcinoma, a form of liver cancer, causing 80 per cent of cases, he noted.   “Having a high viral load in the circulation carries a greater risk of cirrhosis, liver complications and liver cancer” he added.

The disease is transmitted by the same routes as HIV – although it is over 100 times more infectious than HIV -from mother to child during pregnancy and breast-feeding and is also spread between individuals via blood transfusion with contaminated blood products, intravenous drug use via a contaminated needle, or the exchange of bodily fluids in sexual contact including semen, vaginal secretions, saliva, and via open sores.  The risk of contracting HBV following exposure is higher among infants who face a 90 per cent infection rate than adults where the risk is 5 to 10 per cent, he said.

In the the increase in prevalence is already evident, according to Professor Geoffrey Dusheiko, a hepatology specialist from ’s , who says the is seeing around 2000 new cases of hepatitis B per year, the vast majority occurring among recent immigrants. An estimated quarter of a million people in the now carry the infection with about half of these living in .

The most commonly-used treatments available currently show high rates of resistance.  “Close to 100 per cent of patients treated for five years with the most-widely used drug on its own are resistant” he explained. This is leading to a paradigm shift where in future combination therapy at least with older drugs will be the norm despite this going against current guidelines which still advocate sequential use of therapies.  The new drug Baraclude, which is expected to be available in a few months, has so far shown almost zero resistance in clinical trials lasting two years. Baraclude’s molecular action presents a high barrier to gene mutation, he noted.  Clinicians are keen to use the drug which they point out could save costs as well as prevent later complications when used early in a patient’s illness.

The importance of screening groups at risk so that treatment can be offered to those identified with the infection was highlighted during the meeting. Hepatitis B is a silent disease for many years progressing insidiously from inflammation to fibrosis in the liver. “However, offering screening should be done with sensitivity so that people at risk do not feel they are being stigmatised “ said Professor Dusheiko.

London-based Charles Gore, president of the European Liver Patients’ Association said he wants to see uniform action across to ensure all people at risk of hepatitis B infection have equal access to anonymous free testing, vaccination and care to prevent the risk of subsequent liver failure or cancer.

“This is a supranational disease and we can’t prevent it crossing borders” he said.  Ignorance is preventing adequate surveillance from occurring and means that people may go on to develop serious complications that might have been avoided. “We need a pan-European awareness campaign to help identify undiagnosed patients all over the EU and give everyone, including vulnerable groups, equal access to care.” At present access to services in the EU is patchy, he commented. 

Mr Gore also called for action against stigma.  “People with hepatitis B feel stigmatised because the common perception is that this is a disease exclusive to intravenous drug abusers, the sexually promiscuous and illegal immigrants.” This is a myth, he said.  “It not only prevents people coming forward for testing and treatment, it also deters them from speaking to the media so awareness of the condition is not being raised.”  The European Liver Patients’ Association is trying to make sure campaigns to educate the public and encourage screening are focused on the disease itself rather than how it is acquired.  “We should concentrate on the disease rather than apportion blame,” he stressed.

To see more features by Olwen Glynn Owen follow this link to his first feature article and scroll to the end for a list:
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