2025 Hepatitis B Drug Pipeline Update: Hepalatide, AHB-137, and GSK836 Data Deep Dive Accelerates Path to Cure

Recently, the 76th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) concluded in Washington, with a concentrated emergence of global new drug development achievements for hepatitis B. In China,Shanghai Hepu Pharmaceutical Co., Ltd、GSK、Keyuan PharmaceuticalsCompanies have gained significant attention due to breakthrough results, including Hepulapeptide combined with interferon achieving "sterilizing cure" for hepatitis B and AHB-137's sustained clearance rate of 39% after discontinuation. These developments are gradually turning the once seemingly unattainable goal of "clinical cure" into a reality.

1. Hotspots in the Development of New Hepatitis B Drugs in 2025: In-depth Analysis of Key Data from the AASLD Conference

The development of new drugs for hepatitis B has always been a "tough challenge" in the medical field. Compared with previous years, this year's research focus on new hepatitis B drugs has clearly shifted from mere viral suppression to functional cure. Several innovative drugs have shown breakthrough efficacy, especially in terms of HBsAg clearance rates, with multiple drugs reaching new heights, bringing real hope of a cure to patients with hepatitis B. At the same time, exploration of combination therapies with new drugs has notably accelerated. Data shows that many new drugs, as monotherapies, failed to meet primary efficacy endpoints in Phase I or II studies, prompting companies to actively explore various combination treatment regimens.

At present, the research and development direction of new drugs for chronic hepatitis B (CHB) mainly includes entry inhibitors, small interfering RNA (siRNA), antisense oligonucleotides (ASO), HBsAg inhibitors, capsid inhibitors, therapeutic vaccines, Toll-like receptor (TLR) agonists, and immune checkpoint inhibitors, etc. According toMoxie Medical DatabaseStatistics show that currently, more than 150 new hepatitis B drugs worldwide have entered the clinical stage, of which 19 are in Phase III or above, 65 are in Phase II, and 60 are in Phase I.

Global R&D Stage Distribution of New Drugs for Hepatitis B

Source of the image: Mosentropy Medicine - Indication Landscape Database

1.GSK836（Bepirovirsen）

Bepirovirsen is an unbound antisense oligonucleotide targeting all HBV RNAs, currently in Phase III development for the treatment of chronic HBV infection, with a global marketing application expected to be submitted in 2026.

Data from the B-Together (NCT04676724) study showed that some participants receiving NAs treatment achieved complete response (CR) or partial response (PR) after 12 or 24 weeks of bepirovirsen and 24 weeks of sequential treatment with pegylated interferon α-2a (Peg-IFN). This response persisted for 24 weeks after the end of Peg-IFN treatment. Participants who achieved CR or PR were enrolled in the long-term efficacy follow-up study, B-Sure.

This report presents the up-to-2-year response durability follow-up data of CR and PR participants from the B-Together study after entering the B-Sure study. The research data shows that functional cure can be sustained for up to 1 year in CR participants who received sequential treatment with Bepirovirsen combined with Peg-IFN.

2.ZM-H1505R（Canocapavir）

ZM-H1505R (Canocapavir, Conocapavir) isShanghai Zhimeng PharmaceuticalA new generation of virus nucleocapsid inhibitors independently developed, which can effectively inhibit the formation of HBV nucleocapsids as a small molecule candidate compound. Unlike other Type I and Type II HBV capsid assembly modulators under research, Canocapavir is a novel pyrazole-based nucleocapsid inhibitor, offering a completely new mechanism of action compared to existing hepatitis B treatments. Currently, ZM-H1505R is undergoing Phase III clinical trials.

ZM-H1505R Development History in China

Source of the image: Mesentech - Global Drug R&D Database

The Phase II clinical data of ZM-H1505R was published in the AASLD2025 conference abstract. The Canocapavir Phase II study (NCT05484466) aims to evaluate the safety, tolerability, and efficacy of the drug in chronic hepatitis B (CHB) patients with low-level viremia (LLV) treated with entecavir (ETV).

The results indicate that for patients with low-level viremia (LLV) who achieved and maintained HBV DNA levels below 10 IU/mL, the combination therapy of Canocapavir and ETV was generally well-tolerated and effective. The use of Canocapavir in combination with ETV enhanced viral suppression. These findings support the further development of Canocapavir for the treatment of chronic hepatitis B (CHB).

3.GST-HG131

Gushengtang PharmaceuticalThe Phase II study data of GST-HG131, an orally administered small-molecule hepatitis B surface antigen inhibitor, was featured in the latest Late-breaking Abstract and presented on-site. As the world’s first oral HBsAg inhibitor to complete Phase II clinical trials, GST-HG131 significantly enhances patient accessibility and compliance with its convenient oral administration.

In Phase II clinical studies, GST-HG131 reduced serum surface antigen levels by an average of 0.9 logIU/ml from baseline after 12 weeks of treatment in patients, with a maximum reduction of 1.64 logIU/ml; more importantly, GST-HG131 was able to lower the serum surface antigen levels to below 100 IU/ml in 76.5% of hepatitis B patients after just three months of use. Maintaining low surface antigen levels (especially below 100 IU/ml) is of significant importance and value for improving the long-term prognosis of hepatitis B patients, including reducing the incidence of cirrhosis and hepatocellular carcinoma; patients with surface antigen levels below 100 IU/ml are also more sensitive to immune reactivation and more likely to achieve the goal of clinical cure, providing critical support for combined clinical cure strategies.

The Phase II data of GST-HG131 had previously been included in the list of breakthrough therapies by the Center for Drug Evaluation of the National Medical Products Administration in July 2025 due to showing significant clinical advantages. In addition,GSKAnother core inhibitor, GST-HG141, has entered Phase III clinical trials. The dual-drug combination approach directly targets the core of HBV cure, forming a differentiated competitive advantage.

4.HH-003（Libevitug）

Huahui AnjianAt the AASLD 2025 Annual Meeting, in the form of an oral presentation of the latest breakthrough abstract, the 48-week clinical data from the pivotal Phase 2b registrational clinical study (HH003-204) of self-developed Libevirtamab (HH-003) for the treatment of chronic hepatitis D virus (HDV) infection was announced.

Libevitug (Libeveita Monoclonal Antibody, HH-003) is a human monoclonal antibody targeting the pre-S1 domain of the HBV large envelope protein. It has been included in the breakthrough therapy category by China's NMPA and granted Breakthrough Therapy Designation (BTD) by the U.S. FDA for the treatment of chronic HDV infection. Currently, HH-003's hepatitis D and hepatitis B indications are both in the application for marketing stage in China.

HH-003 Review Timeline

Source of the image: Mosana Pharmaceuticals - China Drug Evaluation Database

The results of the HH003-204 study indicate that treatment with Libevirtamab in chronic HDV-infected patients demonstrated statistically significant and clinically meaningful efficacy superior to the control group in terms of composite endpoint response rate, virological suppression, ALT normalization, and improvement in liver stiffness. Both Libevirtamab treatment groups exhibited good tolerability and excellent safety during the 48-week treatment period.

5.AHB-137

AHB-137 isHaobo MedicineAn antisense oligonucleotide drug (ASO) under development has now entered Phase III clinical trials. In HBeAg-negative chronic hepatitis B (CHB) patients, the Phase 2a (NCT06115993) and Phase 2b (NCT06550128) studies, which combined treatment with nucleos(t)ide analogues (NA), demonstrated encouraging efficacy and good safety.

In the abstracts published at the AASLD2025 conference, further disclosure was made regarding the efficacy results of these two Phase II studies at Week 48. The data showed that after discontinuing AHB-137 treatment and continuing nucleos(t)ide analog maintenance therapy for 24 weeks, the aforementioned complete response rates dropped to 22% and 31%, respectively. Additionally, among patients who achieved a complete response at Week 24, only 39% maintained that response at Week 48.

6. Hepalatide

At the conference,Shanghai Hepu Pharmaceutical Co., LtdThe latest research results of two studies on Hepalatide (Hepalatide) were also published.

(1) The combination therapy of Hepalatide and PEG-IFN can effectively reverse the resistance to interferon in HBeAg-positive CHB patients, enhancing the antiviral treatment efficacy. These findings support further evaluation of this combination strategy to improve long-term interferon-based treatment outcomes.

(2) PEG-IFN can promote the degradation of cccDNA by activating the body's immune system, while hepatitis B entry inhibitors can suppress the replenishment of cccDNA by blocking new viral infections. The combination of Hepalatide and PEG-IFN can significantly reduce the level of cccDNA in patients' livers, providing a promising therapeutic strategy for clearing the hepatitis B virus reservoir.

7.BRII-179（VBI-2601）

BRII-179 (VBI-2601) is developed byBrii BiosciencesDevelopment of a Novel Therapeutic Hepatitis B Vaccine for the Treatment of Chronic Hepatitis B: A New HBV Immunotherapy Candidate Based on Recombinant Proteins, Composed of PreS1, PreS2, and S Hepatitis B Virus (HBV) Surface Antigens. Previous clinical trial results have shown that BRII-179 (VBI-2601) can induce strong functional HBV-specific B-cell and T-cell immune responses in a significant portion of virus-suppressed patients with chronic hepatitis B. In November 2023, the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) of China granted BRII-179 Breakthrough Therapy Designation.

At the 2025 AASLDBrii BiosciencesLatest Breakthrough Data from ENSURE II Phase Study Released, Further Highlighting the Potential of BRII-179 as a Curative Therapy for Chronic Hepatitis B. The study showed that participants who developed an anti-HBs response after BRII-179 treatment had significantly higher sustained HBsAg clearance when treated with elebsiran in combination with PEG-IFNα. These data suggest that the immune response induced by BRII-179 may help identify and select patient populations more likely to benefit from curative treatments.

2. Future Prospects of New Hepatitis B Drugs: Combination Therapy Becomes Mainstream Direction

The medical community categorizes hepatitis B cures into two types: functional cure (clearance of serum HBsAg) and sterilizing cure (clearance of intrahepatic cccDNA), with the latter being regarded as the highest standard for a hepatitis B cure and a long-term goal pursued by the medical field.

Data released at this year's AASLD conference shows that hepatitis B treatment is undergoing a historic shift from long-term suppression to functional cure. Drugs such as GSK836, HH-003, ZM-H1505R, and BRII-179 have demonstrated unprecedented curative potential, while combination therapy strategies offer a scientific pathway to achieving higher cure rates.

AsGSKThe "Peak Plan" andBrii BiosciencesAs ENSURE Research Institute shows, future hepatitis B treatments may trend toward the combined use of multi-mechanism drugs, balancing viral suppression with immune reconstruction. As the 2030 global goal of "eliminating viral hepatitis" approaches, China's role in the research and development of new hepatitis B drugs is becoming increasingly prominent. From the sterilizing cure breakthrough of Heplapeptide to the durable response of AHB-137, domestically produced innovative drugs are aligning with international frontiers in "real-time," bringing genuine hope of a cure to hundreds of millions of hepatitis B patients worldwide.

Attachment: Global New Drug Development Progress for Hepatitis B (As of October 2025)

       Title: 2025 HBV New Drug Updates | Full Interpretation of Hepplaptide, AHB-137, and GSK836 Data, Accelerating HBV Cure