Two Hepatitis B ASO Therapies Set for BLA in 2026: Bepirovirsen and AHB-137 Show Promising Functional Cure Data

At the recently held annual meeting of the American Association for the Study of Liver Diseases（AASLD 2025）Above, the latest clinical data for two hepatitis B small nucleic acid drugs —— Bepirovirsen and AHB-137 —— were respectively announced.

Small nucleic acid drugs mainly include small interfering RNA（siRNA）And antisense oligonucleotides（ASO）Among them, ASO is a class of single-stranded RNA that mainly targets HBV mRNA or pre-mRNA through the base complementary pairing principle, inhibiting viral protein synthesis. The two drugs mentioned above both belong to ASO drugs and have demonstrated significant HBsAg clearance ability and response durability in clinical settings.

Bepirovirsen, jointly developed by GSK and Ionis（GSK836）It is one of the fastest-progressing ASO drugs for hepatitis B, and has entered phase 3 clinical trials.Expected to submit marketing application in China by 2026。

The previously conducted B-Together study showed that, in nucleoside(Acid)Analogue（NA）In the treatment of patients with chronic hepatitis B, 12 or 24 weeks of Bepirovirsen combined with 24 weeks of long-acting interferon was adopted.（Peg-IFN α-2a）Sequential treatment can lead to complete response in some patients.（CR）And Partial Response（PR）, and the response should be sustained until 24 weeks after discontinuation of interferon.

Based on this, these responders were included in the B-SURE study for long-term follow-up to evaluate the persistence of functional cure after discontinuation. The results presented at AASLD 2025 are from the long-term extension follow-up of the B-SURE study.

The study results showed that 12 out of 13 CR patients discontinued NA, and 75% remained in CR six months after discontinuation.(Functional Cure)；At 12 months, 87.5% of patients maintained functional cure; At 18 months, 100%(2/2）Patients maintained functional cure. Reasons for the loss of CR in 3 patients included HBsAg reversion or withdrawal from the study; none of the CR patients restarted treatment during the study period.

In terms of safety, no significant ALT elevation was observed in all patients after discontinuation of the drug, and no new safety signals were identified.

The latest data shows that most CR patients treated with Bepirovirsen combined with Peg-IFN sequential therapy achieved functional cure.Lasting at least 1 year。

AHB-137 is a non-conjugated ASO drug developed by a team in China. According to Haobo Medicine, AHB-137 adoptsThe Third Generation Chemical Modification Technology(such as phosphorothioate backbone and 2'-MOE modification), significantly enhancing the stability and liver-targeting of the drug, reducing systemic side effects, and improving therapeutic efficacy.

Based on the significant advantages shown in early-phase 1/2a clinical data, AHB-137 was granted Breakthrough Therapy designation by the CDE in July of last year. On July 22, 2025, AHB-137 received NMPA approval to proceed with Phase 3 clinical trials.

At the AASLD 2025 conference, Haobo Medicine presented two multicenter, randomized Phase 2 clinical studies.(Phase 2a NCT06115993 and Phase 2b NCT06550128)The 48-week data summary analysis results.

Specifically, ABH-137 at 24 weeks after the end of treatment(Week 48)Demonstrated strong and sustained antiviral response, including complete response(HBsAg < 0.05 IU/mL and HBV DNA < LLOQ)Partial Response(HBsAg < 10 IU/mL and HBV DNA < LLOQ)。

Among them, inIn the regimen of 300 mg over 24 weeks, the patient response rate was the highest., and this efficacy was consistent across different baseline HBsAg level strata. Moreover, AHB-137 was generally well-tolerated, with no new safety signals observed after the end of treatment.

These positive data provide strong support for further advancing AHB-137 toward functional cure of chronic hepatitis B, also demonstrating the powerful potential of China-developed ASO new drugs for hepatitis B to achieve functional cure.

Although ASO drugs are one step ahead in Phase 3 clinical trials, siRNA therapy, another type of small nucleic acid drug, is also progressing rapidly and represents another important direction for achieving functional cure of hepatitis B. The mechanism of action of siRNA is similar to that of ASO, but it is double-stranded RNA, which guides the degradation of target mRNA through the RNA interference mechanism, thereby inhibiting the synthesis of viral proteins such as HBsAg.

Currently, although no relevant pipeline has entered the critical Phase 3, quite a few pipelines are already in Phase 2, such asElebsiran from Brii Biosciences/Vir/Alnylam, BW-20507 from Bowang Pharmaceutical, HT-101 from Stargo Kunze, RBD1016 from Ribo Biotech, AB-729 from Qilu Pharmaceutical/Arbutus, HRS-5635 from Hengrui Medicine, TQA3038 from Zhengdatianqing, GSK5637608 from GSKEtc.

Chinese companies stand out in this field.

BW-20507 is a GalNAc-conjugated siRNA drug developed by Bowang Pharmaceutical, targeting the S region of mRNA. Published Phase 1/2 clinical data shows that subcutaneous injection of BW-20507 significantly reduces HBsAg levels in a dose-dependent manner, with the maximum reduction observed being 2.9~3.2 log10 IU/mL in the 200 mg and 400 mg dose groups. In subjects with baseline HBsAg levels below 1000 IU/mL,56%HBsAg clearance occurred during the study period.

In June 2025, BW-20507 received NMPA approval for Phase 2 clinical trials. On September 8, Bowang Pharmaceutical announced the completion of the first patient dosing in the Phase 2 clinical trial of BW-20507.

HT-101 is the first China-produced anti-hepatitis B siRNA new drug to enter the clinical stage. It inhibits hepatitis B virus particle formation by interfering with HBV mRNA, disrupting its function as a post-transcriptional translation template, and preventing the synthesis of related viral proteins.

Previously, the Phase 1b clinical study published by Stargo Kunge showed that all subjects in the HT-101 treatment group who participated in the extension phase maintained a significant reduction in HBsAg levels at 48 weeks. Notably, in the 400 mg dose group, one subject achieved HBsAg clearance after receiving two doses and undergoing 48 weeks of follow-up.

At the AASLD 2025 Annual Meeting, the research team reported the results of a Phase 1b/2a clinical trial combining HT-101 with the fully human neutralizing antibody HT-102. The results showed that, compared to monotherapy, this combination therapy led to a rapid, deep, and sustained reduction in HBsAg; in the high-dose group, there was...90%Of the patients, HBsAg clearance was achieved at week 20, with 20% of participants achieving HBsAg clearance as early as week 4.。

The aforementioned clinical results led to the formal inclusion of HT-101 and HT-102 products in the "Breakthrough Therapy Designation" on September 23, 2025. Currently, the Phase 2b RCT trial for the combination of HT-101 and HT-102 is ongoing.

In addition to the aforementioned pipelines, there are also several small nucleic acid pipelines in China at early clinical/preclinical stages for the treatment of chronic hepatitis B, which will not be elaborated here.

With the rapid development of various innovative therapies such as ASO and siRNA, the path to functional cure for hepatitis B is becoming increasingly clear. Based on the current progress of research and development, if all goes smoothly, the first hepatitis B ASO drug could be submitted for marketing approval as early as 2026.

For hundreds of millions of hepatitis B patients worldwide, these breakthrough advances mean that the landscape of hepatitis B treatment is undergoing a fundamental shift, with the hope of making a "cure" truly an attainable reality.

Shanghai Zhaowei Technology

Shanghai Zhaowei Technology Development Co., Ltd. has been deeply engaged in the nucleic acid field since its establishment in 1998. The company has established mRNAA CDMO and small nucleic acid drug CDMO full industry chain platform, with a production base for small nucleic acid drugs at a ton-scale or above, providing services to customers.Providing development and production services from preclinical to commercialization stages, the independently developed enzymatic synthesis process technology has achieved public availability globally for the first time.Industrial production at the jin-level scale.

The company also has a phosphoramidite product line with an annual capacity of 58 tons, and raw material capacity supporting over 10.5 billion doses of mRNA vaccines.The company has established long-term cooperative relationships with biotechnology and pharmaceutical companies around the world, providing services for numerous clinical-stage and commercialized nucleic acids.Pipeline supplies raw materials.

For more information about Zhaowei Technology and its products and services, please visit the official website www.hongene.com and follow our WeChat Official Account "Shanghai Zhaowei Hongene".」。

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References:

1.Official Websites and Official WeChat Accounts of Various Companies

2. Public Information

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