Functional cure found for fifth of people living with Hepatitis B

A new study published in The New England Journal of Medicine has shown success in treating people living with chronic Hepatitis B.

The investigational agent, bepirovirsen, has been shown to offer a functional cure in one in five people, offering hope to many living with this chronic condition.

But how did they do it?

Produced by GSK, bepirovirsen is an antisense oligonucleotide. This compound interferes with the ability of the Hepatitis B virus to replicate. It binds to viral mRNA and stimulates an immune response, allowing the patient’s body to attack the virus.

A functional cure is different from a full cure, where the virus is removed from the body. Rather, it means the virus is controlled so well that it cannot be detected in the blood using key markers, even after treatment has stopped.

In this context, a functional cure means sustained loss of Hepatitis B surface antigen (HBsAg) and HBV DNA below the lower limit of quantification for at least 24 weeks after fixed-duration therapy. This is important because HBsAg loss is linked with better long-term outcomes, but it’s rarely achieved with current treatments.

Bepirovirsen doesn’t eliminate a form of HBV DNA hidden in the nucleus of liver cells. This is why it is considered a functional cure, rather than a sterilising cure.

The study reported results from two large, double-blind phase 3 trials called B-Well 1 and B-Well 2. Together, they included more than 1,800 adults with non-cirrhotic chronic Hepatitis B who were already receiving stable nucleoside or nucleotide analogue therapy. Participants received either weekly injections of 300 mg bepirovirsen or placebo for 24 weeks, while continuing their existing antiviral treatment throughout the trial.

At week 72, significantly more people who received bepirovirsen achieved a functional cure than those who received a placebo. In B-Well 1, 127 of 650 people treated with bepirovirsen achieved a functional cure, compared with none of the 328 people in the placebo group.

In B-Well 2, 106 of 570 people treated with bepirovirsen achieved a functional cure, compared with none of 286 people in the placebo group. This equates to around 20% and 19% of bepirovirsen-treated participants, respectively.

The response was even higher among people who started with lower HBsAg levels. In pooled data, patients with baseline HBsAg levels of 1,000 IU/ml or less had a functional cure rate of around 26%.

The study also reported more side effects among people receiving bepirovirsen, including injection-site reactions and raised alanine aminotransferase (ALT) levels, a liver enzyme that can rise when the liver is inflamed or under stress.

For people living with chronic Hepatitis B, these findings are encouraging. Current antiviral treatments can suppress the virus but are usually long-term and rarely lead to HBsAg loss. A 24-week course of bepirovirsen helped around one in five eligible participants reach functional cure, suggesting that some people may be able to control the infection without ongoing daily antiviral therapy.

However, bepirovirsen is still an investigational medicine and is not yet a routine treatment option. More follow-up will also be needed to understand how durable the functional cure is over the longer term and which patients are most likely to benefit.

Is bepirovirsen a complete cure for Hepatitis B?

No. The study looked at functional cure, not complete eradication of the virus. Functional cure means key blood markers of active infection remain undetectable for a sustained period after treatment has stopped.

How many people achieved functional cure?

Across the two phase 3 trials, around 19% to 20% of people receiving bepirovirsen achieved functional cure at week 72, compared with 0% of people receiving placebo.

Mike Asher, CEO of Better2Know, had this to say of the advancement.

“I’m always amazed at the advances medical science continues to make. We at Better2Know welcome these advances in treatment. Hepatitis B can ruin lives, and any advancements that help people better navigate their condition will provide benefits to many. We hope such advancements help raise awareness of the need to increase public awareness of this infection so that people will keep getting tested to learn about their sexual health status.”

If you’re concerned about your sexual health in any way, Better2Know is here to help. Call the number listed at the top of this page to speak to one of our trained Sexual Health Advisors.