Hepatitis B Infection 100% Eliminated With Cancer Drug Combination In Preclinical Model

A cancer drug was 100 percent successful in clearing away hepatitis B infections in preclinical models for an Australian study. If researchers successfully replicate the results in human clinical trials, the drug may become the first-ever cure to the hepatitis B virus and may serve as a model for treating other viruses, such as HIV and herpes.

Researchers at the Walter and Eliza Hall Institute in Melbourne, Australia used a combination of the cancer drug birinapant and the antiviral drug entecavir to completely eliminate hepatitis B infections in “hundreds of tests in preclinical models,” lead researcher Dr. Marc Pellegrini explained in a press release. Human trials began in December 2014, and drug testing has currently moved on to a phase 1/2a in clinical trials. 

Hepatitis B is a viral infection that attacks the liver. It is transmitted via contact with infected blood or bodily fluids and causes chronic liver infection, which may lead to life-threatening cirrhosis or liver cancer. According to the World Health Organization, there are an estimated 240 million people who are chronically infected with hepatitis B, and around 780,000 people die from complications due to their infection each year.

Although a vaccine against the virus has been available since 1982, treatment of those who are already infected is limited. This is because the virus is able to override the liver’s self-preservation mechanism. Normally, at the sign of infection, the liver will switch on a signal that tells cells to self-destruct in order to prevent further infection, Pelligrini explained. The hepatitis B virus destroys this communications switch and tells the cells to ignore rather than fight the infection. Birinapant is able to reverse this viral override, and restore the liver’s natural infection-fighting defense.

"Birinapant flips the cell survival 'switch' used by the virus, causing the infected cell to die," Pelligrini said.

The team also found that when birinapant was used in combination with entecavir, the infection was cleared twice as fast. 

Drug resistance is an ever-present challenge for doctors when it comes to treating viruses. A virus learns to adapt to drugs and then becomes resistant to their defense. However, because the new combination indirectly attacks the virus by changing the way the body responds, this problem will most likely not exist.

“The virus relies on the survival mechanisms of the host, so if it can't exploit them, it dies. Such a monumental change in the virus's environment may be too big a hurdle for it to adapt to,” Pelegrini added.

The team believes the unique method in which the drug works could be used to explore effective treatments for other viruses such as HIV, herpes, dengue fever, and even bacterial infections such as tuberculosis.

Pellegrini, Dr. Greg Ebert, and their colleagues at the institute have published their research on the new drug combination in two papers in the online journal Proceedings of the National Academy of Sciences. Patients are being recruited to partake in the clinical trials in hospitals located in Perth and Adelaide, Australia. 

Source: Pellegrini M, et al. Proceedings of the National Academy of Sciences. 2015.