Add-on treatment brings functional cure to hepatitis B patients
Bepirovirsen benefits 19% of patients in Phase 3 clinical trials
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Nearly one in five people with chronic hepatitis B who were given add-on treatment with GlaxoSmithKline (GSK)’s bepirovirsen in two global clinical trials achieved a functional cure.
GSK announced earlier this year that the Phase 3 clinical trials B-Well 1 (NCT05630807) and B-Well 2 (NCT05630820) had hit their main goal, showing bepirovirsen outperformed a placebo at promoting a functional cure in people with chronic hepatitis B.
A functional cure is defined as undetectable levels of hepatitis B virus (HBV) DNA and hepatitis B surface antigen (HBsAg) in the blood for at least 24 weeks (about six months) after stopping all treatment.
Now, full results from the trials have been published in The New England Journal of Medicine, in the study “Phase 3 Results of Bepirovirsen Treatment for Chronic Hepatitis B Virus Infection,” and presented at the European Association for the Study of the Liver Congress, held May 27-30 in Barcelona.
Based on positive data from these trials, GSK has filed applications seeking approval of bepirovirsen in the U.S., Europe, Canada, China, and Japan. The U.S. Food and Drug Administration (FDA) is expected to make a decision by Oct. 26.
“CHB [Chronic hepatitis B] affects over 240 million people worldwide and accounts for over half of global liver cancer cases,” Tony Wood, PhD, GSK’s chief scientific officer, said in a company press release. “For the first time, bepirovirsen offers the possibility of significantly better functional cure rates than the current standard of care, and the potential to reduce the risk of long-term liver complications, including cancer.”
Hepatitis B is a viral infection that affects the liver. Standard treatments, including nucleos(t)ide analogs (NAs), can help control HBV, but patients usually have to keep taking these treatments for life to prevent the infection from worsening. Rates of functional cure are reported in fewer than 1% of cases, according to GSK.
“Today’s standard of care for CHB imposes a heavy burden on patients and healthcare systems, and rarely delivers a functional cure,” said Jinlin Hou, MD, the study’s first author and a professor at Guangdong Institute of Hepatology in China.
Bepirovirsen, being developed in partnership with Ionis Pharmaceuticals, comprises a small piece of genetic material designed to target HBV genetic material for destruction. The aim is to suppress viral replication and production of viral proteins, potentially helping the immune system regain control of the infection and increase chances of a functional cure.
The Phase 3 B-Well studies enrolled nearly 2,000 people with chronic hepatitis B who had blood levels of the viral protein HBsAg between 100 and 3,000 international units per milliliter (IU/mL).
Participants were randomly assigned to receive an under-the-skin injection of either bepirovirsen or a placebo once a week for about six months, in addition to their standard-of-care NAs.
The studies’ main goal was to see how many participants achieved a functional cure after about 1.5 years of follow-up. Pooled data showed that, across both studies, 233 (19%) of 1,220 of the patients given bepirovirsen achieved a functional cure. In contrast, none of the 614 participants on the placebo attained that outcome.
Even higher rates of functional cure, at 26%, were observed in participants with HBsAg levels of 1,000 IU/mL or lower — a subgroup that “represents approximately 45% of diagnosed CHB cases globally,” the company said. This meant the trial met one of its key secondary goals.
Among patients with HBsAg levels greater than 1,000 IU/mL, between 5% and 10% of those treated with bepirovirsen across the two trials achieved a functional cure.
Bepirovirsen also outperformed the placebo on two other key secondary measures that evaluated the proportion of patients showing sustained decreases in blood levels of HBV DNA below the limit of detection after discontinuation of all treatments. This rate was 23% for all bepirovirsen-treated patients and 31% for those showing HBsAg levels up to 1,000 IU/mL. No participant given the placebo met these outcomes.
“With recent guidelines now prioritising functional cure, these new data could represent an important advance,” Hou said. “Combined with improved testing and diagnosis, this innovation has the potential to improve the lives of millions living with CHB.”
Pooled rates of adverse events were higher in the bepirovirsen groups than in the placebo groups (91% vs. 73%), as were those of severe adverse events (7% vs. 4%). The most commonly reported adverse events among participants treated with bepirovirsen were injection side reactions. Most of these events were nonserious and were managed with monitoring and pausing treatment where necessary.
Adverse events led to treatment discontinuation in 3% of participants. Two patients given bepirovirsen died during the study, but both deaths were judged to be unrelated to the treatment.
