Scientists Develop New Drug Class to Combat Hepatitis B

The fight against the Hepatitis B virus (HBV) has taken a significant step forward with the development of a new class of drugs known as RNA interference (RNAi) therapeutics. This innovation aims to improve treatment outcomes for the approximately 256 million people worldwide living with chronic HBV infections. The findings were published in Science Translational Medicine by a team of scientists, leading to optimism about a potential functional cure for this life-threatening virus.

Chronic HBV infection is responsible for more than one million deaths each year, often leading to severe health complications such as liver damage, cirrhosis, and liver cancer. While effective vaccines and treatments exist, the virus remains elusive, particularly in patients infected as infants, who may carry the infection for decades. According to John Tavis, Ph.D., a professor at Saint Louis University School of Medicine and a co-author of the paper, a functional cure would involve eliminating viral DNA and a protein known as surface antigen from the bloodstream for at least six months post-therapy.

“A functional cure means eliminating the viral DNA and a viral protein called the surface antigen, which accumulates in high levels in the bloodstream,” Tavis explained. He emphasized that achieving this not only reduces the chances of the virus re-emerging but also lowers the risk of future health complications.

Despite the progress, Tavis cautioned that the term “cure” is somewhat misleading. While most adults who contract HBV clear the infection naturally, some retain a replication-competent virus that can reactivate, especially in immunocompromised individuals. Additionally, fragments of viral DNA can integrate into a person’s genome, producing viral antigens that may lead to cancer.

Combining Forces Against HBV

The researchers propose that a multi-faceted approach involving combination therapies could pave the way for a more effective treatment strategy. Current methods include replication inhibitors and drugs that target viral antigen production. A third component would stimulate the immune system to enhance the body’s ability to combat the virus effectively.

The team believes that viral antigens not only play a role in the virus’s replication but also suppress the immune response. Tavis noted, “If you suppress the immune system, your body has a hard time controlling the infection. It’s like your body is fighting the virus with one hand behind its back.”

Excitement surrounds specific RNAi drugs, particularly Bepirovirsen, developed by GlaxoSmithKline. This drug not only suppresses HBV for extended periods after treatment ceases but also activates the immune system, providing a dual action against the infection.

“We want to turn down the smokescreen that the virus is putting up, by getting rid of the antigens, while simultaneously blocking viral replication,” Tavis added. The goal is to combine these strategies to clear the virus effectively.

In clinical trials, the most promising combination therapies that include RNAi drugs currently show a success rate of 30% in achieving a functional cure after about a year to a year and a half of treatment. This represents a substantial improvement compared to the 5% success rate of standard care options.

Looking Ahead

While researchers acknowledge that there is still a long way to go, the progress made thus far is encouraging. The complexity of HBV and its interactions with the immune system pose significant challenges, but the innovative strategies being explored provide hope for millions affected by this chronic infection.

“Though we’re not there yet, it’s very promising given the complexity of what we’re facing,” Tavis remarked. The potential for a functional cure could not only save countless lives but could also limit the spread of HBV globally.

As researchers continue to explore these new therapeutic avenues, the scientific community remains hopeful about making strides toward a world where Hepatitis B is no longer a pervasive public health threat.

Further details on this groundbreaking research can be found in the study by Matteo Iannacone and colleagues, titled “Targeting HBV with RNA interference: Paths to cure,” published in Science Translational Medicine in 2025.