Bristol-Myers Squibb’s new antiviral medication Baraclude should quickly become established as the first-line agent of choice for treating people with hepatitis B virus infection, thanks to its potency and low propensity to cause resistance.

That is the view of Alfredo Alberti of the University of Padova in Italy, who presented clinical data on the drug, just approved for marketing in Europe, at the International Symposium on Viral Hepatitis and Liver Disease in Paris yesterday.

The clinical profile of Baraclude (entecavir triphosphate) also makes it an ideal core agent for use in combination therapy for HBV, a treatment paradigm that is just starting to be proposed for HBV patients.

Baraclude has been launched into a marketplace currently dominated by GlaxoSmithKline’s Zeffix (lamivudine), the most widely-used agent, as well as Gilead Sciences’ Hepsera (adefovir dipivoxil). But B-MS’ product has data showing that it is more effective than lamivudine in completely clearing virus from the blood.

Baraclude was approved last March in the USA and made just $5 million in 2005, although momentum behind the product seems to be growing with $11 million in first-quarter 2006 sales. Meanwhile, Zeffix turnover came in at $67 million in the first quarter, while Hepsera made $43 million.

Alberti noted that Baraclude answers some of the current limitations of oral antiviral therapy for HBV, including a lack of potency, limited responses and a high resistance rate, while the other treatment option, interferon alfa therapy, is really only suitable for a subgroup of patients and has a response rate of just 20%-30%.

“Entecavir should substitute for lamivudine in treatment, compete with adefovir in lamivudine-resistant patients and reduce the use of interferon in HBV patients,” he told journalists at the ISVHLD.

Geoffrey Dusheiko of the Royal Free Hospital in London told PharmaTimes that no mutations conferring resistance to entecavir have been identified in patients who have not already received treatment with lamivudine, so it appears that the genetic barrier to resistance with the drug is high.

“But it is likely just a matter of time for resistance to develop,” he said, adding that the emergence of resistance will probably be the prompt for studies to test combination therapies, with greater antiviral activity that should make the stimulation of resistance mutations in HBV less likely.

Baraclude is due to be tested in combination with either adefovir or tenofovir, according to Richard Colonno, vice president of infectious disease drug discovery at B-MS.

He also told PharmaTimes that three-year data on the drug would be presented later this year at the American Association for the Study of Liver Diseases conference in Boston, and B-MS is planning to continue studies out to 5-8 years in order to gauge the effects of the drug on clinical outcomes such as cirrhosis and liver cancer.


The incidence and prevalence of HBV is rising in Europe, mainly because of high levels of immigration from areas of the world where the disease is more widespread, according to Dusheiko, and he called for a targeted screening campaign to help identify and treat carriers of the virus.

This should concentrate on groups such as migrant populations, as well as other, higher-risk groups such as intravenous drug users, although he acknowledged this is a sensitive issue and would have to be handled carefully to stigmatisation.

84% of the six million increase in the UK’s population in recent years has come from immigration, he noted, and the newcomers, often young and sexually active “are the people we are seeing in our clinics.” The benefits of screening just need to be explained clearly, he said.

Dusheiko also said it is unfortunate that the UK is one of only a handful of developed countries that does not provide routine immunisation against HBV as part of its childhood vaccination programme.