“It’s a real milestone — the first treatment to hit functional cure as its main goal in two large phase 3 trials. But a milestone for science isn’t the same as helping most patients. It suits only a small group — low-antigen, no cirrhosis, already diagnosed and treated with antivirals. The real gap is diagnosis, not cure. Everybody must get tested for Hepatitis B at least once in their lifetime,” says Dr Cyriac Abby Philips, known as the Liver Doctor, and senior consultant at The Liver Institute, Rajagiri Hospital, Kochi. Excerpts:

What does “functional cure” mean and how is it different from killing the virus?

A functional cure means that, after a fixed course of treatment, you stop all drugs and the virus stays controlled on its own — the virus’ surface antigen (any substance that the immune system can recognize and respond to like molecules found on the surface of viruses, bacteria, fungi and parasites) remains undetectable and viral DNA will be too low to measure, for at least 24 weeks off treatment. It does not mean the virus is gone.

Hepatitis B leaves a permanent template inside each liver-cell nucleus and even integrates bits of its DNA into the person’s own genes. No drug removes those. So the virus is silenced, not eliminated — it can reactivate if the immune system is later suppressed, and monitoring must continue. A “complete cure” that clears every trace isn’t possible yet.

Why did only about 20% of patients achieve a functional cure with bepirovirsen, and are there characteristics that predict who is most likely to benefit?

The biggest factor is how much the virus’ surface antigen you start with. In people starting at 1,000 IU/mL or below, cure rates were 25% and 28%; in those at 1,000–3,000, they fell to 10% and 5%. The drug lowers the virus antigen and helps wake up the immune system, and the less antigen at the start, the easier it is to push to zero. Everyone in the trial was already without cirrhosis and well-controlled on antiviral therapy. So the real benefit sits in the low-antigen group — the 20% average hides that. Even there, immune differences we can’t fully predict mean most patients still aren’t cured fully.

Can patients stop lifelong antivirals? How long does the drug’s effect last?

Responders stopped their pills at week 48 and only counted as cured if they stayed virus-free for 24 more weeks off everything. The catch is durability: so far we’ve only confirmed about six months off treatment. We don’t know the 3-, 5- or 10-year picture; the hepatitis B virus antigen can return later. One encouraging early sign: of the 62 who stopped their pills without a full cure, only five had detectable viral DNA and none became clinically ill. Bottom line: Cured doesn’t mean cured forever, and it doesn’t mean no follow-up — liver cancer surveillance has to continue.

How does bepirovirsen compare with current treatments?

Today’s drugs (tenofovir, entecavir) are taken for life and rarely cure anyone — under 1% achieve a functional cure. Bepirovirsen, in 24 weeks, cured about 20% (25–28% in low-antigen patients) versus zero on placebo. That’s a big jump.

As for safety, it’s harder on the body than a daily pill. Side effects hit 91% versus 73% on placebo; serious ones 7% versus 4%; severe ones 16% versus 3%, mostly liver-enzyme flares in about 6%, and 3% stopped because of them. Liver, kidney and platelet changes need close monitoring.

The upside is that the drug’s finite — no lifelong pills, no daily cost, no resistance worry, and it removes the “incurable” label. But it’s weekly injections for six months with frequent blood tests, not a single shot.

Which patients need it first?

The same people as in the trial: no cirrhosis, already controlled on antivirals, with low surface antigen (≤3,000, ideally ≤1,000). It wasn’t tested in people with cirrhosis, HIV coinfection or hepatitis B virus antigen above 3,000, so it shouldn’t be used in them yet. The US is first in line — the FDA fast-tracked it and a decision is due by October 26. In practice, big hospitals and liver centres that can give the injections and do the monitoring; the rollout may be slow because of testing and monitoring capacity.

Does it cut the risk of cirrhosis and liver cancer, and by how much?

Almost certainly it lowers the risk — but this trial can’t tell you by how much. It measured the virus at 72 weeks, not actual cirrhosis or cancer, and the follow-up is too short. From other studies, losing the hepatitis B surface antigen from blood gives the best outcomes and clearly reduces cirrhosis and cancer — but not to zero, because the hidden virus stays. People with existing liver scarring or older age can still develop cancer, so surveillance should be continued. In short: a big reduction, not elimination, and no exact figure for this drug yet.

Is this drug a gamecanger? How affordable can it be?

There are three problems. It suits only a small group — low-antigen, no cirrhosis, already diagnosed and treated with antivirals. The real gap is diagnosis, not cure. Of the 254 million people with hepatitis B, only about 13% are diagnosed and roughly 3% are on treatment. Most of the burden is in countries like India and China, where most people are never tested. A drug for already-treated patients can’t reach them.

No price yet but these drugs are expensive and it’s expected to be a blockbuster, over $2 billion in peak sales. Likely affordable in rich systems for the right patient, but probably out of reach for the poorer countries that carry most of the disease, which also often lack the injection-and-monitoring set-up.So, yes, a genuine breakthrough but not yet a fix for the global epidemic without affordable pricing and far better testing.