Experimental drug offers ‘functional cure’ for one in five chronic hepatitis B cases

A new experimental drug was found to functionally cure one in five people with non-cirrhotic chronic hepatitis B virus (HBV) infection in two phase 3 trials.

The drug, bepirovirsen, which was given as a 300mg weekly dose, successfully suppressed the virus and eliminated the hepatitis B surface antigen in as many as 20% of the trial candidates.

Vanessa Hebditch, director of policy at the British Liver Trust, said the findings were an ‘encouraging step’ towards therapies that could fundamentally change the course of the disease.

She added: ‘Patients with hepatitis B have been waiting decades for treatments that do more than keep the virus under control.

‘With more than 268,000 people in the UK estimated to be living with hepatitis B, continued investment in better treatments, alongside improved testing and diagnosis, remains vital.’

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Hepatitis B is a serious liver infection spread through contact with blood or other bodily fluids. According to the American Liver Foundation, the best way to prevent infection with hepatitis B virus is by getting the hepatitis B virus vaccine, which is highly effective.

For those who are unvaccinated, 95% of healthy adults who contract HBV will naturally clear the infection within six months and develop lifelong immunity.

However, for some the condition becomes chronic and lifelong treatment is required to suppress the virus. Chronic HBV can lead to cirrhosis – scarring – of the liver, liver cancer, and liver failure.

The new study, published in The New England Journal of Medicine and funded by GSK, was composed of two replicate, double-blind, placebo-controlled phase 3 trials called B-Well 1 and B-Well 2.

The trial enrolled 1,834 patients across 29 countries. To be eligible participants had to be receiving stable nucleoside or nucleotide analogue therapy – the standard treatment for HBV – and have an HBsAg level below 3,000 IU/mL at baseline.

In addition to standard nucleotide analogue therapy, patients were randomised two-to-one to receive either a 300mg weekly dose of subcutaneous bepirovirsen or placebo for 24 weeks.

The authors said that the primary outcome of the trials was a functional cure at week 72, defined as the virus no longer being detected in the blood – measured by the sustained loss of hepatitis B surface antigen and the HBV DNA being undetectable for at least 24 weeks after a finite course of treatment.

Compared with zero patients in either placebo group, 20% of bepirovirsen patients in B-Well 1 and 19% in B-Well 2 achieved a functional cure.

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Furthermore, around 23% of patients in both intervention groups maintained suppressed HBV DNA after stopping nucleotide analogue therapy at week 48 – which was a key secondary outcome of the study.

In January, when the preliminary results of these phase 3 trials were first announced, Tony Wood, chief scientific officer at GSK, said: ‘Bepirovirsen has the potential to transform treatment goals for people living with CHB [chronic hepatitis B] by achieving significant functional cure rates – a first for the disease.

‘CHB affects more than 250 million people and leads to approximately 56% of liver cancer cases worldwide.

‘Today’s result supports our plans to progress bepirovirsen as a treatment and also continue its development as a backbone in future sequential therapies.’

According to the researchers, adverse events were more frequent with bepirovirsen than with placebo, with 91% of the patients in the bepirovirsen groups and in 73% of those in the placebo groups reporting adverse events.

Of these events, injection-site reactions were the most common – occurring in 53% of the patients in the bepirovirsen groups and in 14% of those in the placebo groups. These reactions mostly occurred during the first four weeks of treatment and the majority were classed as mild.

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Serious adverse events occurred in 7% of participants in the bepirovirsen group and 4% of those in the placebo group. Adverse events that led to permanent treatment discontinuation occurred in 3% of the patients in the bepirovirsen groups.

A version of this article was first published on our sister title, The Pharmacist.