A study published May 28, 2026 in the New England Journal of Medicine, presented simultaneously at the European Association for the Study of the Liver Congress in Milan, has reported that a drug called bepirovirsen achieved a functional cure in 19% of patients in two large phase 3 clinical trials, with rates rising to 26% in patients with lower baseline viral protein levels.
Bepirovirsen has now become the first anti-hepatitis B therapy to complete global phase 3 trials with functional cure as the primary outcome, a finding with potentially transformative implications for a disease in which no approved finite therapy currently exists.
For most of the people in those trials, that means something that has never been possible before: finishing a course of treatment and having the virus genuinely controlled, without medication, for at least six months.
Against a disease where that outcome was previously achieved in less than 1% of treated patients, these numbers represent an entirely different category of result.
Why hepatitis B has been so much harder to cure than hepatitis C
To understand the significance of this breakthrough, you need to understand a comparison that haunts the hepatitis B field.
In 2013, the FDA approved sofosbuvir (Sovaldi) for hepatitis C.
Within a few years, hepatitis C, once considered a chronic incurable infection, was being cured in 90 to 99% of patients with a short course of oral medication.
The medical world celebrated it as one of the great pharmaceutical achievements of the modern era.
Hepatitis B researchers watched from the sidelines, asked when their equivalent would arrive, and had no good answer.
The reason the two diseases have responded so differently to treatment comes down to a single biological feature: a molecule called covalently closed circular DNA, or cccDNA.
A major obstacle in achieving a hepatitis B cure is the presence of cccDNA in the hepatocyte nucleus.
When hepatitis B infects a liver cell, it does not simply replicate in the cytoplasm and move on.
It inserts a miniature, extremely stable chromosome into the nucleus of the cell itself.
That cccDNA sits inside the nucleus like a viral instruction manual, directing the production of new viral proteins and new viral particles for as long as the cell lives.
The persistence and stability of cccDNA within hepatocytes makes it the greatest obstacle to achieving a complete cure for chronic hepatitis B, because current antiviral therapy is efficient in inhibiting viral replication but has only a marginal effect on cccDNA production, stability, or transcription.
Existing drugs called nucleotide analogues (NAs), including tenofovir and entecavir, suppress HBV replication very effectively.
They can reduce viral load to undetectable levels.
But they cannot eliminate cccDNA.
The moment a patient stops taking them, the virus rebounds.
It is estimated that it would take a median of 36 to 52 years before surface antigen clearance would be attained with standard NA therapy alone.
That is not a treatment.
That is life management.
And for hundreds of millions of people, it means a daily pill forever, with the risk of cirrhosis and liver cancer always present in the background.
How the B-Well trials were conducted
The phase 3 program consisted of two identical, replicate randomized double-blind placebo-controlled trials: B-Well 1 and B-Well 2.
Together they enrolled more than 1,800 patients across 29 countries, making this one of the largest and most geographically diverse hepatitis B trials ever conducted.
Eligible patients were adults with noncirrhotic chronic HBV infection who were receiving stable nucleoside or nucleotide analogue therapy and had a surface antigen level between 100 and 3,000 IU per milliliter.
Two-thirds of participants received weekly subcutaneous injections of bepirovirsen for 24 weeks, added to their standard NA therapy.
The remaining one-third received placebo injections plus their existing medication.
All participants continued NA therapy through week 48, at which point eligible patients discontinued all HBV treatment.
The primary outcome was assessed at week 72: 24 weeks after all treatment had stopped.
Functional cure was defined strictly as undetectable HBV DNA and loss of the hepatitis B surface antigen (HBsAg), the viral protein that signals ongoing infection.
That 24-week drug-free window is what distinguishes a functional cure from simple viral suppression.
It means the immune system has taken over.
The virus is being controlled by the patient’s own biology, not by medication.
In two phase 3 trials involving patients with chronic HBV infection, a functional cure after the discontinuation of NA therapy was reported in significantly more patients treated with bepirovirsen than in those who received placebo, with zero participants in the placebo arms achieving functional cure.
Zero in the placebo arms.
Every single functional cure in those trials came from bepirovirsen.
What bepirovirsen actually does
Bepirovirsen is not a conventional antiviral.
It belongs to a class of molecules called antisense oligonucleotides (ASOs): short, precisely engineered sequences of genetic material designed to bind to specific RNA sequences and disable them.
Bepirovirsen is an antisense oligonucleotide that binds to HBV messenger RNA, preventing the virus from making needed proteins and triggering its destruction, while separately stimulating immune responses against the virus.
That dual action is what makes it biologically distinct from every approved hepatitis B drug.
Standard NAs block the virus from copying its DNA.
Bepirovirsen goes further upstream, targeting the messenger RNA that the cccDNA produces and preventing it from being translated into viral proteins at all.
Without its surface antigen and other structural proteins, the virus cannot assemble new particles.
Without the persistent immunological tolerance that high levels of surface antigen create, the immune system can begin to mount a proper response.
HBV RNA transcript degradation lowers viral proteins including HBsAg, potentially reversing immune tolerance and enabling durable immune control beyond NA-mediated DNA suppression.
This immune re-awakening is the mechanism that underpins the functional cure concept.
The virus is not eliminated entirely.
The cccDNA remains in liver cells.
But the immune system recovers its ability to control the infection, and it maintains that control after medication stops, the same way the immune system of a healthy adult controls thousands of other viral exposures throughout a lifetime.
What the results actually mean
The findings are described as remarkable and a major step forward for the field, with the functional cure rate going up to 26% in participants who entered the study with the lowest levels of the viral surface antigen.
At first glance, 19% might seem like a modest headline.
It is not 90%.
It is not the 95% that sofosbuvir delivers for hepatitis C.
But the comparison to previous hepatitis B treatment outcomes is the right frame.
The current standard of care for hepatitis B often requires lifelong therapy and functional cure rates remain low, typically only 1% per year.
A 19% functional cure rate, in patients who had previously been destined for lifetime medication, is a nineteen-fold improvement over the baseline.
And the results held across both independent replicate trials, in the same patient population, at the same effect size.
That replication is one of the most important features of the data.
In clinical research, a single positive trial can reflect real efficacy or can reflect statistical chance.
Two independent trials producing identical results in the same direction, simultaneously, in over 1,800 patients across 29 countries, is not a coincidence.
The biological problem bepirovirsen cannot yet solve
Here is where the research requires an honest and careful reading, because the term “functional cure” can sound more definitive than the biology it describes.
Like existing nucleotide analogue drugs, bepirovirsen does not eliminate the embedded cccDNA, which is considered a sterilizing cure, but it helps suppress HBV levels low enough for long enough to reinvigorate immune responses against the virus.
The cccDNA remains.
The virus is not eradicated.
A small reservoir of infected liver cells, each carrying that stable viral chromosome, persists after treatment.
The question that drives the entire durability debate is what happens when those cells eventually regenerate, or when the immune system’s vigilance lapses years later.
Whether a bepirovirsen-induced functional cure is lifelong remains a key issue, and the durability of surface antigen loss requires further assessment through extended follow-up, though data from earlier phase 2 studies have shown viral suppression for up to three years in more than 90% of functionally cured patients.
Three years of maintained functional cure in 90% of patients from the earlier trials is genuinely encouraging.
But hepatitis B is a disease measured in decades, and three years is not decades.
The patients from the B-Well trials will be followed for years to come, and those durability data will ultimately be more important than the week 72 snapshot in determining what bepirovirsen’s long-term impact really is.
The bigger story: why hepatitis B has been neglected for so long
Here is where the science becomes a social and political story, and the two are impossible to separate.
Hepatitis B is disproportionately a disease of the developing world.
There were an estimated 240 million people living with chronic HBV infection globally in 2024, and the WHO African Region accounted for 68% of all new HBV infections.
Chronic HBV infection caused about 1.1 million deaths in 2024, an increase of 17% since 2015, despite the availability of effective suppressive therapy.
The World Health Organization estimates that only 27% of infected people have been diagnosed, and of those, fewer than 5% receive treatment.
Read those numbers together.
A disease affecting 240 million people.
Only 27% diagnosed.
Of those, fewer than 5% treated.
The pharmaceutical infrastructure, the diagnostic capacity, and the healthcare access needed to reach the remaining 95% simply do not exist in many of the places where the disease is most concentrated.
And into this landscape comes a drug developed by GSK and Ionis Pharmaceuticals, delivered as weekly subcutaneous injections for 24 weeks, which has not yet had its price announced.
GSK has stated it is committed to pricing which balances the value of innovation and patient access, and will work constructively with payers around the world to achieve this, but has yet to announce how much the drug will sell for in wealthy countries or resource-limited ones.
The hepatitis C story is instructive here.
Sofosbuvir, when approved in 2013, was priced at approximately $84,000 for a 12-week course in the United States.
For several years, it remained largely inaccessible in the countries where hepatitis C burden was highest.
It took years of negotiation, generic manufacturing agreements, and international pressure to make it available in lower-income countries at prices that allowed meaningful scale.
Hepatitis B advocates and global health researchers are watching the bepirovirsen pricing announcement with precisely that history in mind.
A drug that cures 19% of an easily-treated subset of a disease affecting 240 million people, the majority of whom are in low and middle-income countries, is only a public health breakthrough if the public that bears the disease can actually access it.
What kind of functional cure this actually is, and why it matters
The language of “functional cure” deserves careful unpacking, because it is doing significant work in describing what bepirovirsen achieves.
In hepatitis B medicine, a functional cure means something specific and meaningful.
It means the virus cannot be detected in the blood.
It means the surface antigen, the viral protein that signals active infection, has cleared.
It means the immune system has been restored to a state where it can control the infection without pharmaceutical support.
Functional cure is associated with significant reduction in the risk of long-term liver complications including liver cancer, as well as all-cause mortality.
That last sentence is the one that matters most to patients.
Functional cure is not just a biochemical endpoint.
It means a dramatically reduced risk of developing cirrhosis, the slow scarring of liver tissue that eventually makes it unable to function.
It means a dramatically reduced risk of hepatocellular carcinoma, one of the most lethal and fastest-growing cancers in the world.
Chronic hepatitis B accounts for approximately 56% of all liver cancer cases worldwide, making it the single largest driver of a cancer that kills more than 800,000 people per year globally.
The 81% of B-Well participants who did not achieve functional cure are not failures of the drug.
Many of them will still have benefited from the viral suppression and immune stimulation the treatment produced.
But the research community is unanimous that reaching functional cure rates of 19% to 26% in the currently treatable population is a threshold moment, not an endpoint.
Some hepatitis B researchers remain frustrated that pharmaceutical companies have not made more collaborative efforts to design truly curative drugs, with the field’s view being that a cure for many patients will require a multiprong approach combining different mechanisms simultaneously.
What comes next, and who benefits
Bepirovirsen is currently under priority review by the FDA with both Breakthrough and Fast Track Designation, with a target action date of October 26, 2026.
It is also under review by regulatory authorities in Europe, Japan with SENKU designation, and China with Breakthrough Therapy and Priority Review designation, with GSK anticipating the first regulatory decisions in Q3 2026 and launch preparations already underway.
If approved on schedule, bepirovirsen could reach patients in the United States, Europe, Japan, and China within the next twelve months.
The harder question is when it reaches the patients in West Africa, Southeast Asia, and Pacific Island nations who carry the heaviest burden of the disease.
That question will be answered not by the phase 3 data but by a combination of pricing decisions, generic licensing agreements, and global health funding mechanisms that are still being negotiated.
What the science has delivered is unambiguous: a mechanism that meaningfully achieves what the hepatitis B field has been attempting to accomplish for 60 years.
A finite course of treatment.
A functioning immune system taking over.
A 19-fold improvement on the baseline.
For a disease that was long expected to require lifelong medication and still be fatal for millions, that is not a modest result.
It is the door finally opening.
What happens after depends on who is allowed to walk through it.
Sources:
Cohen J. New drug ‘functionally cures’ many hepatitis B virus infections. Science. May 28, 2026.
WHO. Global Hepatitis Report 2026.
PMC. Targeting HBV cccDNA levels: key to achieving complete cure of chronic hepatitis B. 2025.
Hepatology. Global burden of HBV-related liver disease: primary liver cancer. November 2025.
