Clinical trial results support bepirovirsen for hepatitis B
Add-on treatment led to higher functional cure rates in Phase 3 trials
Written by |
Bepirovirsen added to standard-of-care medications led to higher functional cure rates for people with chronic hepatitis B than standard treatments alone, according to top-line results from two Phase 3 clinical trials.
GlaxoSmithKline (GSK), which is developing bepirovirsen under a collaborative development and licensing agreement with Ionis Pharmaceuticals, said it will use the results to support regulatory submissions seeking the treatment’s approval worldwide.
“Bepirovirsen has the potential to transform treatment goals for people living with [chronic hepatitis B] by achieving significant functional cure rates – a first for the disease,” Tony Wood, PhD, GSK’s chief scientific officer, said in a company press release. “Today’s result supports our plans to progress bepirovirsen as a treatment and also continue its development as a backbone in future sequential therapies.”
Hepatitis B is a viral infection transmitted through contact with bodily fluids that causes inflammation in the liver. Some people, particularly those infected early in life, develop a chronic or long-lasting infection.
Chronic hepatitis B “affects more than 250 million people and leads to approximately 56% of liver cancer cases worldwide,” Wood said.
Trials spanned 29 countries
Bepirovirsen is an antisense oligonucleotide (ASO), or a short piece of lab-made genetic material, designed to destroy the hepatitis B virus’ messenger RNA. Messenger RNA, or mRNA, is an intermediary molecule produced when DNA is read to make a protein. By targeting the virus’ mRNA, the therapy aims to shut down the production of new viral proteins.
“Bepirovirsen is uniquely positioned to effectively treat CHB based on its potential to reduce the replication of hepatitis B virus,” Brett P. Monia, PhD, CEO of Ionis, said in a company press release.
The trials, B-Well 1 (NCT05630807) and B-Well 2 (NCT05630820), collectively enrolled more than 1,800 people with chronic hepatitis B across 29 countries, who were randomly assigned to receive either bepirovirsen or a placebo.
All participants also received standard-of-care treatment with oral nucleoside/nucleotide analogues (NAs), a class of antiviral medicines that stop the virus from replicating its DNA.
The studies’ main goal was to see if add-on treatment with bepirovirsen led to higher functional cure rates. A functional cure means that the viral protein HBsAg and viral DNA are undetectable for 24 weeks (about six months) after completing treatment, allowing the immune system to control the infection without additional treatments.
People with chronic hepatitis B who achieve a functional cure are at significantly lower risk of liver cancer and other serious health problems.
GSK said both trials met that goal, with significantly higher functional cure rates observed in patients given add-on bepirovirsen compared with those on standard therapies alone.
While the trials enrolled people with up to 3000 international units (IU)/ml of the viral protein HBsAg in their blood, participants with levels of 1000 IU/ml or lower experienced greater benefits from bepirovirsen, which was a key secondary goal.
GSK said bepirovirsen showed an acceptable safety and tolerability profile, consistent with prior studies. The company didn’t provide further specifics, noting that details will be presented at an upcoming scientific meeting and published in a peer-reviewed journal.
Monia said the results “demonstrate that bepirovirsen has the potential to bring hope to the millions of people living with CHB.”
The U.S. Food and Drug Administration (FDA) has granted bepirovirsen fast track designation, a status designed to speed the development of promising new therapies.
