Only 20 percent fictional cure rate?
Presentation is here https://assets.gskstatic.com/corporate/Congress/2026/EASL/DV-020652-AN.mp4
The full paper is also published in the NEJM for anyone who is interested https://www.nejm.org/doi/full/10.1056/NEJMoa2515131
It’s not all bad news, though the functional cure rate of patients between 1000-3000 HBsAg is disappointing for sure. I think we will eventually find a way to cure those patients, though it will likely require some sort of combination therapy.
I agree with @et5656. Although this will help a small portion of patients, I still think it is a step in the right direction. If 20% of 240 million people do achieve long-lasting functional cure status, that is 48 million people who could be spared cirrhosis and HCC. Definitely, all is not lost; what I see as the biggest challenges are accessibility and cost. If those persist, then the impact of Bepi could be limited. Bansah1
@Bansah1 the NYT article is a bit misleading. The data presented showed that the mean surface antigen level of the patients in this trial was around 1,000. People with HBsAg > 3000 were excluded from the trial. So this is not saying that bepi will cure 20% of patients overall. I still hope that it’s good enough for it to be approved, because I still think it’s as good as, or better than PEG-IFN, with a shorter course of treatment, and it seems like less severe side effects.
I think the functional cure rate was about 26% for surface antigen less than 1000 in thepresentation. I was just making the point that if it’s at 20%, that is about 48 million people. Still not bad, if the status of functional cure is long-lasting.
HI all,
Overall, I agree with @Bansah1. This is not as high a functional cure rate as I was hoping for, but ~20% is still a really nice advance compared to the current standard of care. That is especially true as the patients were treated with just Bepi and nuc analogs. Adding a complementary drug, or perhaps even lengthening the treatment period, would likely push more patients into the cure range.
There’s a lot more work to do, but let’s celebrate the advance that this research represents!
John.
At minute 5.15 of the presentation. I hope I interpreted it correctly. That’s the functional cure rate broken down into regions right?. I am wondering why there is a difference across regions for both groups. I initially thought maybe it’s to do with geno type, but wouldn’t Asia- Pacific have the same geno type to China, therefore similar functional cure rate?. Then there’s Europe-Turkey that’s in line with Asia - Pacific, but different to America and China.
Anyway can someone shed some light please. Thank you:)
Encouraging! Definitely promising and hopeful.
Very exciting!! Some of us, including @ThomasTu, are at EASL and were in Dr. Sengee Lim’s presentation of this data. This is the first new drug for HBV in 10 years! (It’s not yet approved, but we expect FDA’s decision in October)
Agree! It’s not as high as we’d like but its better than what we currently have. Hopefully this is the start of more drugs coming down the pipeline that will get better with time.
That’s awesome!! I wasn’t able to come to Barcelona, but I paid for online access and watched it first thing in the morning when I woke up. Cure rates are not as high as I would have hoped, but I still hope the drug gets approved.
Also important to note that 63% of the study participants had HBsAg < 1000.
I’m extremely happy with the results. I think 20% is a good number for a mono therapy on virally suppressed patients. And the fact that they were working with people with Hbsag up to 3000 also seems encouraging
And from my limited understanding it seems to be targeting a genetically conserved region so the concern with the quasi species mutation thing seems to be a non issue
I’ll be curious to see how different dosing protocols might help different kinds of patients. Let alone other drug combinations. One thing that comes to mind is I wonder how this would compliment the NUC stop protocol? Or even trying tapering? It gives the community a whole new modality to employ
The fact that it’s hard to manufacture correctly (so I don’t know if there’ll be generics) and that it’s an injection (which also limits distribution) are the things which I wish were a little better
Hi @bob,
The study was further stratified with patients who have HBsAg < 1000, and patients between 1000-3000. The cure rate was not equal between these two groups. Unfortunately, only 7% of patients in the 1000-3000 group achieved functional cure (33/452), compared to 26% (200/768) in the <1000 group. I’m actually kind of disappointed about the 7% number. I hoped it would be above 10% for that group of patients.
I was on bepirovirsen last year as part of a different study (I have a whole thread about that). The B-Well study presented at EASL did involve stopping NUCs for those who remained HBsAg negative 24 weeks after ending treatment with bepi. There definitely won’t be generics available any time soon, because the drug will be under patent if it’s approved. I also have concerns about distribution. My study coordinator told me one day that the drug needs to be stored frozen until it’s used. She said that once it thaws, it has to be used within 4 hours, and cannot be re-frozen. I’m not sure if it requires an ultra-cold -70 degree laboratory grade freezer, or if a standard household freezer is cold enough. This is something that could certainly affect distribution though. I also think that given some of the side effects observed, it would be important for patients to undergo CBC and CMP panels regularly while on treatment to check blood counts, liver enzymes and kidney function. Access and logistics for blood tests is also a challenge. Overall, kind of a mixed bag. I still think that bepi is better than the options we have currently, and I hope it gets approved.
I read in the article that 49% of patients in the study ended up reaching <100 iu/ml HBSAG. If that number holds, thats actually pretty good in itself.
@Mike2 Yes, that is true. Even a partial response (sustained HBsAg <100) shouldn’t be considered a failure. When the next drug comes out, it could be significantly easier to cure those partial responders.
Well done everyone for generating and contributing so such a great summary of the presentation! I came here thinking I would have to do a whole bunch of work to convey this study to community, but you’ve already beat me to it (with all very reasonable interpretations).
Some additional aspects that I think might be important to note:
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Done in ~1000 people from different countries - 2 replicate studies separately analysed showing that it isn’t just a fluke
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~25% HBsAg loss in people with HBsAg <1000 (~1/6 to ~1/4 of all people with Hep B who are eligible - that is on nuc therapy without decomp cirrhosis)
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~19% HBsAg loss in people with HBsAg <3000 (1/3 of all people with Hep B who are eligible )
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7% loss in people with HBsAg 1000-3000 (suggests that 1000 will be the cut off because anything over 1000 has a low chance of working)
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The higher the ALT flares, the better the chance of HBsAg loss - we will need education/promotion around this maybe with a message that “liver flares can be associated with “good” results and means the medication is working”
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There may be a monitoring phase (blood tests to ensure it’s working and remains safe) and dosing schedule (clinic- or self-administered injections, cold chain required) that means it can’t be rolled out everywhere. I think what these phases end up being will be subject to a whole bunch of regulatory, legal, clinical, scientific, pathology, and financial factors.
Cheers,
Thomas
Cheers,
Thomas
Thank you @ThomasTu for the additional information! I didn’t catch the part about higher ALT flare = better. I found this chart in the appendices, but unfortunately, it’s showing whether the patients reached undetectable HBsAg at any visit, not just the ones who had functional cure. If you have a similar chart (but showing people who achieved functional cure, instead of just HBsAg <0.05 at any visit), please do share!
Is it certain that the cold chain is going to be necessary? I was under the impression that this class of drugs is usually stable at room temperature for a few days. And I assumed that the cold storage was used just to remove a variable for the trial. I could be totally wrong though, it’d be good to know