GSK's Bepirovirsen Shows Promise in Hep B Functional Cure Trials
GSK's bepirovirsen just hit its primary endpoint in two massive Phase 3 trials, functionally curing roughly one in five chronic hepatitis B patients after just six months of treatment. In a disease affecting 254 million people with zero approved cures, that's a very big deal.
254 Million People, Zero Cures
Imagine being told you have a chronic disease, handed a pill bottle, and informed you'll need to refill it every month for the rest of your life. No finish line. No graduation day. Just pills, forever.
That's the reality for the roughly 254 million people worldwide living with chronic hepatitis B. The virus slowly damages the liver, raising the risk of cirrhosis and liver cancer. Current treatments (drugs called nucleoside analogues, or NAs) do a solid job of suppressing the virus, but they almost never eliminate it. Stop taking them, and the virus roars back. Functional cure rates on these drugs sit in the low single digits, even after years of use.
So when GSK announced positive Phase 3 results for its experimental drug bepirovirsen, the hepatitis B world took notice.
What "Functional Cure" Actually Means
Let's be precise, because the word "cure" does a lot of heavy lifting here.
Functional cure in hepatitis B means two things happen simultaneously: the viral surface protein (called HBsAg, the calling card the virus uses to dodge your immune system) disappears from your blood, and viral DNA drops to undetectable levels. Crucially, both of those have to stay that way for at least 24 weeks after you stop treatment. No more pills. No safety net.
Think of it like training wheels on a bike. Current drugs are the training wheels; they keep you upright, but only while they're attached. Functional cure means you can ride on your own.
The virus technically still lurks in liver cells in a dormant form, so "functional cure" isn't total eradication. But patients who achieve it have dramatically lower risks of liver cancer and can stop therapy entirely. In a disease where lifelong medication is the norm, that's transformative.
The Drug That Attacks HBV Three Ways
Bepirovirsen is what scientists call an antisense oligonucleotide (ASO). In plain English: it's a small piece of synthetic genetic material designed to stick to the virus's own RNA and destroy it.
Get tomorrow's biotech intelligence before your competitors.
Join thousands of biotech professionals who start their day with our free, daily briefing.
GSK describes bepirovirsen as a "triple action" therapy because it does three things at once. First, it degrades the virus's messenger RNA, cutting off the instructions the virus uses to make copies of itself. Second, it slashes production of HBsAg, the surface protein that acts like a cloak of invisibility, exhausting the immune system and preventing it from fighting back. Third, by lowering that protein burden, bepirovirsen lets the immune system wake up and regain control of the infection on its own.
It's a clever strategy: weaken the virus, strip its disguise, then let the body's own defenses finish the job.
The Trial Results That Turned Heads
GSK ran two massive Phase 3 trials, called B-Well 1 and B-Well 2, enrolling more than 1,800 patients across 29 countries. Both trials were randomized, double-blind, and placebo-controlled (the gold standard of clinical research).
Patients received bepirovirsen on top of their existing NA therapy, then had their background treatment gradually withdrawn to see if the cure would hold. Both trials hit their primary endpoint: bepirovirsen plus standard care produced a statistically significant, clinically meaningful functional cure rate compared to standard care alone.
The effect was strongest in patients who started with lower levels of HBsAg (below 1,000 IU/mL), consistent with what GSK saw in its earlier Phase 2 trial, B-Clear. That study, published in the New England Journal of Medicine, showed roughly 10% functional cure overall, climbing to about 25% in patients with low baseline HBsAg. The Phase 3 results appear to confirm and extend that pattern.
For context, the functional cure rate on standard NA therapy alone? Barely a blip. We're talking low single digits over many years.
Why Wall Street Is Paying Attention
Analysts had been watching this program closely, and the Phase 3 win triggered a wave of commentary.
Jefferies analyst Michael Leuchten described the data as encouraging, saying it should open blockbuster potential, noting that no existing therapy offers meaningful functional cure. William Blair's team described bepirovirsen as an "underappreciated opportunity" that had been under-modeled by the Street. J.P. Morgan struck a more cautious tone, labeling the readout a "slight positive" while noting that investors will want to see the full dataset before getting too excited.
The commercial math is straightforward. GSK has guided that bepirovirsen could generate over £2 billion in peak annual sales. That figure sits within the company's broader target of exceeding £40 billion in total revenue by 2031. For a disease affecting a quarter of a billion people globally, even capturing a fraction of the addressable market would be enormous.
Regulatory momentum is building fast. The FDA has accepted a priority review application with Breakthrough Therapy designation. The EMA has accepted a marketing authorization application in Europe. And in Japan, bepirovirsen received SENKU designation (an expedited review pathway) and had its NDA accepted in February 2026.
The Race Is Far From Over
GSK isn't the only company chasing a hepatitis B cure. The competitive landscape is heating up, and the field is converging on a shared playbook: knock down viral proteins with RNA-targeting drugs, then let the immune system clean up.
GSK actually holds two cards in this game. Alongside bepirovirsen (the ASO), it licensed exclusive worldwide rights to daplusiran (an siRNA, or RNA interference drug, originally developed by Arrowhead Pharmaceuticals and previously known as JNJ-3989) through a licensing agreement with Janssen in 2023. The two drugs attack viral RNA through different mechanisms, and GSK is exploring sequential regimens that combine them.
Meanwhile, Vir Biotechnology is advancing its own siRNA (elebsiran) paired with an anti-HBsAg antibody. Arbutus Biopharma plans a Phase IIb trial of its siRNA, imdusiran, in the first half of 2025. And in China, Amoytop Biotech already won approval for Pegbing, which reportedly achieved a 31.4% clinical cure rate in its pivotal study.
Companies like Assembly Biosciences and Aligos Therapeutics are working on capsid assembly modulators, small molecules that block viral replication through a different mechanism. They're more likely to serve as combination partners than standalone cures, but they add important pieces to the puzzle.
The Big Picture
Exact Phase 3 cure percentages have not yet been publicly disclosed, and the drug works best in a specific subset (those with lower HBsAg levels), which means the real-world eligible population will be smaller than the full 254 million.
But perspective matters. For decades, chronic hepatitis B has been a disease you managed, never one you beat. Bepirovirsen offers something that didn't exist before: a finite, six-month treatment with a real shot at walking away from the virus entirely.
Full Phase 3 data are expected at the EASL 2026 congress later this year, along with a peer-reviewed publication. Those details (exact cure percentages by subgroup, long-term durability, safety signals) will determine whether this drug lives up to its blockbuster billing or settles into a more modest role.
Either way, the era of "take this pill forever" in hepatitis B may finally be ending. For a disease with no cure at all, these results are a beginning.
Clinical & Regulatory4 min read
A Tiny Korean Biotech Just Put Up MASH Numbers That Rival Novo Nordisk
A small Korean biotech just dropped MASH liver disease data that looks competitive with Novo Nordisk's blockbuster semaglutide. The catch? Only 35 patients were in the trial, and the competition is about to get fierce.
