Race to Hepatitis B Functional Cure: Five Leading Pipelines Nearing Approval in 2026

The Marathon Toward Clinical Cure for Hepatitis B Is Nearing the Finish Line. Chinese Faces Feature Prominently in This Historic, Milestone-Level Breakthrough in New Drug Development.

The European Association for the Study of the Liver Annual Meeting 2026 (EASL 2026), held in Barcelona, Spain, in late May, became a global showcase for novel hepatitis B therapies, with multiple new drugs aiming for clinical cure releasing pivotal data.

Global Phase III clinical trial data for the blockbuster drug bepirovirsen were presented at the conference, whileProfessor Hou Jinlin from the Department of Infectious Diseases, Nanfang Hospital of Southern Medical University, is the Core Principal Investigator (Core PI) of this study, and the related research findings alsoPublished in The New England Journal of Medicine (NEJM).

Key B-Well data show that the overall study population achieved a significant clinical cure rate of 19%, with a clinical cure rate of up to 26% in patients with lower viral activity, compared to 0% in those receiving standard therapy alone.

The competitive landscape is not limited to overseas companies; several domestic enterprises have also achieved breakthroughs in the clinical cure of hepatitis B, with AusperBio, Brii Biosciences, and Hengrui Pharma delivering new progress.

Achieving a clinical cure for hepatitis B is associated with a significant reduction in the risk of long-term liver complications, including hepatocellular carcinoma. The severe situation in China, characterized by persistently high incidence rates of liver cancer, has made achieving a clinical cure an urgent priority.

Hepatitis B is the most prevalent chronic viral disease worldwide, with over 240 million people globally affected by chronic hepatitis B (CHB). It is estimated that there are approximately 75 million individuals infected with the hepatitis B virus in China, and more than 450,000 hepatitis B-related deaths occur annually in the country.

Although China has shed the label of being a country with a high prevalence of hepatitis B, the proportion of liver cancer and cirrhosis caused by hepatitis B remains high.The situation is grim. According to data from Brii Biosciences’ prospectus, globally, 45% and 30% of patients with primary liver cancer and cirrhosis, respectively, are caused by HBV infection. In China, the proportions are 80% for primary liver cancer and 60% for cirrhosis.

The difficulty in curing hepatitis B is associated with integrated DNA and cccDNA. After infecting hepatocytes, the hepatitis B virus (HBV) can integrate its viral DNA into the host genome and form covalently closed circular DNA (cccDNA) within the cells. Both integrated DNA and cccDNA can persist long-term in infected hepatocytes and are difficult to eradicate completely, thereby enabling the persistence of chronic hepatitis B (CHB).

Furthermore, hepatitis B virus produces large amounts of circulating surface antigens, as well as other proteins. These hepatitis B virus products are immunosuppressive, and long-term high levels of‌Hepatitis B surface antigen (HBsAg) will lead to T cell exhaustion and weakened autoimmunity. This is an important reason why CHB is difficult to cure.

Existing nucleos(t)ide analogs intervene at a late stage in the viral life cycle, inhibiting viral DNA replication. However, they do not affect the transcriptional activity of cccDNA or the production of viral proteins, and rarely induce immune control. Long-term treatment is required, and the risk of drug resistance makes achieving HBsAg clearance difficult.

Another class of drugs, long-acting interferons, possesses both antiviral and immune-activating effects and can achieve clinical cure in some patients; however, their use is limited by a small responsive population, prolonged treatment duration, and significant side effects.

Therefore, the clinical cure of hepatitis B has become the holy grail in the global pursuit of new drugs for the disease. The criteria are extremely stringent: HBV DNA and HBsAg must remain undetectable in the blood for at least six months after cessation of all treatment.

Clinical cure of hepatitis B not only resolves the issue of long-term medication but also significantly reduces the risk of developing liver cirrhosis and hepatocellular carcinoma.

This clinical need is urgent in China, where patients demonstrate a strong willingness to pay for therapies that offer a clinical cure.For example, although interferon, the only currently approved drug for curing hepatitis B, has significant side effects and a low cure rate, a considerable number of patients in China still attempt to use it as a potential functional cure therapy.

To achieve a clinical cure for hepatitis B, companies worldwide have explored various approaches.Pathway 1: Striking at the Viral Core by Targeting the HBV Life Cycle.From the moment the virus enters hepatocytes, every stage—replication, assembly, and release—is guarded by new drugs. These include entry inhibitors, cccDNA inhibitors, RNA interference agents (small interfering RNA [siRNA], antisense oligonucleotides [ASO]), capsid inhibitors, and HBsAg inhibitors (nucleic acid polymers [NAPs]).

Pathway 2: Awakening the Immune Army—Targeting the Host Immune System,IncludingTherapeutic vaccines, monoclonal antibodies, TLR-7/8 agonists, and PD-(L)1 inhibitors... These drugs aim to dismantle the "immune fog" laid by HBsAg, restore the combat effectiveness of T cells, and enable the body itself to become the ultimate weapon for eradicating the virus.

Among novel therapeutics targeting different mechanisms for the clinical cure of hepatitis B, small interfering RNA (siRNA) and antisense oligonucleotides (ASOs) demonstrate more significant effects in reducing HBsAg levels.

Furthermore, since the clinical cure of hepatitis B requires the dual clearance of hepatitis B surface antigen (HBsAg) and hepatitis B virus DNA (HBV DNA), along with long-term maintenance of efficacy after discontinuation of treatment, achieving a high-efficacy cure for hepatitis B will inevitably involve combination therapy with multiple classes of drugs. Research on combination therapies involving agents with different mechanisms of action is actively underway. In addition to combinations of novel agents, studies combining new drugs with pegylated interferon-alpha (PEG-IFNα) are increasingly common. According to disclosed interim data, combination therapy with novel agents and PEG-IFNα helps further reduce HBsAg levels and sustain therapeutic effects. The exploration of various combination regimens will represent the future trend toward achieving comprehensive clinical cures for hepatitis B.

There are over 40 hepatitis B cure pipelines under investigation globally; VCBeat has compiled the five most notable late-stage clinical pipelines worth watching.

Bepirovirsen (bepirovirsen injection) is undoubtedly the most watched pipeline in the global field of clinical cure for hepatitis B. Backed by GSK, its research and development progress is leading, and it has been included in priority review in multiple countries including China and the United States, with marketing applications submitted.

Chia Tai Tianqing is optimistic about the sales potential of Bepirovirsen in the Chinese market and entered into a partnership with GSK in May 2026 to secure its commercialization rights in China.

As an antisense oligonucleotide (ASO) drug with a triple mechanism of action, bepirovirsen features a base sequence complementary to HBV RNA. Upon entering hepatocytes, it forms a double-stranded structure with the target mRNA, leading to RNase H-mediated degradation. This process inhibits viral DNA replication, reduces HBsAg levels, creates a window for immune system recovery, and enhances the likelihood of a durable response.

In the pivotal Phase III clinical trials, both the B-Well 1 and B-Well 2 studies met their primary endpoints. Pooled data from the two trials demonstrated that 6 months of bepirovirsen treatment achieved statistically and clinically significant outcomes in the overall study population (adults with hepatitis B surface antigen [HBsAg] levels ≤3000 IU/mL).19% Clinical Cure Rate, achieving the primary endpoint.

In terms of regulatory approval, GSK has submitted a marketing application to the FDA, with a final decision expected on October 26, 2026. At that time, whether Bepirovirsen can become the first drug approved in the U.S. will be a key focus for the industry.

Bepirovirsen has also submitted a marketing authorization application in China and has been included in the priority review program. On May 25, the National Medical Products Administration (NMPA) released information on the delivery of drug notification documents, which included Bepirovirsen; this was interpreted as the application not having been approved. On May 27, GSK resubmitted its marketing authorization application.

Industry insiders revealed that the initial application was not rejected due to issues with efficacy, safety, or data, but rather due to systemic problems. The resubmitted marketing application did not include additional technical documents, and the priority review status remains intact. Consequently, the originally scheduled market launch in the first quarter of 2027 has not been affected.

In the ASO drug race for hepatitis B, Bepirovirsen is not the only standout; Chinese pipelines are also highly competitive. Among the three ASO therapies for clinical cure of hepatitis B with the most advanced global clinical progress, the domestically developed AHB-137 holds a place. AHB-137 is from AusperBio (Hangzhou).

AusperBio’s AHB-137 is a non-conjugated antisense oligonucleotide (ASO) drug that also features a triple mechanism of action, aiming to achieve a clinical cure for chronic hepatitis B.

AHB-137 has demonstrated positive clinical efficacy in multiple clinical studies. In 2026, AHB-137 presented the final follow-up data from its Phase II clinical trial in treatment-naïve chronic hepatitis B patients (without nucleos(t)ide analogue background therapy) for the first time at the European Association for the Study of the Liver (EASL).

AHB-137 monotherapy demonstrates a rapid onset of action, achieving potent suppression of HBV DNA and HBsAg clearance within 16 weeks of treatment. Follow-up data at 24 weeks post-treatment discontinuation indicate that virologic response and antigen clearance status are durably maintained after cessation of therapy. At 24 weeks post-discontinuation, the overall population (i.e., baseline HBsAg 100–10,000 IU/mL)32% of patients achieved clinical cure (FC)Among patients with baseline HBsAg levels of 100–1,000 IU/mL, the clinical cure rate was 70%. Among patients with baseline HBsAg levels >1,000 IU/mL, 33% achieved a state of “partial cure” (sustained suppression of HBV DNA and HBsAg <10 IU/mL).

Industry insiders stated, “In the research consensus among China, the United States, and Europe, a clinical cure rate of approximately 30% is widely regarded as a key milestone signifying a major breakthrough in curative therapies. To date, AusperBio’s AHB-137 is the first monotherapy to achieve this breakthrough in the primary target population of hepatitis B patients.”

AHB-137 has completed its global Phase I clinical trial and is currently advancing multiple global Phase II clinical trials as well as a Phase III clinical trial in China.

siRNA is also a key technological approach in the development of drugs for the clinical cure of hepatitis B.. The therapeutic mechanisms of siRNA and ASO are similar, both aiming to target mRNA through sequence complementarity.

Compared with ASO drugs, novel siRNA drugs for the clinical cure of hepatitis B have a faster onset of action and a lower dosing frequency; however, more clinical data are needed to substantiate their therapeutic efficacy.

Johnson & Johnson, Hengrui Pharma, Qilu Pharmaceutical, Ribo Life Science, Bowang Pharma, Chia Tai Tianqing, Xingyao Kunze, and other companies are developing siRNA drugs for hepatitis B treatment. Among them, Hengrui Pharma’s HRS-5635 has advanced to Phase III trials first.

HRS-5635 is a small interfering RNA (siRNA) drug independently developed by Hengrui Pharma for the treatment of chronic hepatitis B. HRS-5635 is a novel covalently conjugated, triantennary N-acetylgalactosamine (GalNAc)-linked double-stranded siRNA. It achieves selective delivery into hepatocytes through the binding of GalNAc to the asialoglycoprotein receptor (ASGPR) on the surface of liver cells. Within hepatocytes, it specifically targets HBV via the RNA interference (RNAi) pathway, inhibiting the expression of HBV-related proteins and exerting antiviral effects.

Phase II clinical study results of HRS-5635 monotherapy for chronic hepatitis B demonstrate its potential to enhance clinical cure rates, along with a favorable safety profile, expected to provide additional treatment options for patients with chronic hepatitis B.

The R&D focus of siRNA drugs is primarily on combination therapy. Hengrui Pharma’s Phase II study of HRS-5635 in combination with PEG-IFNα for the treatment of chronic hepatitis B is currently underway.

In terms of progress, this drug has entered Phase III clinical trials. The Phase III trial plans to enroll 540 subjects with chronic hepatitis B and is expected to be completed by June 2028.

Another Star Drug for the Clinical Cure of Hepatitis B Using siRNA: VIR-2218 (ALN-HBV02, elebsiran)VIR-2218 was developed by Vir Biotechnology. In 2020, Brii Biosciences obtained the exclusive rights to develop and commercialize elebsiran in the Greater China region from Vir Biotechnology.

Elebsiran is an investigational small interfering RNA (siRNA) drug administered via subcutaneous injection, targeting the hepatitis B virus (HBV). It is designed to degrade HBV RNA transcripts and limit the production of hepatitis B surface antigen, demonstrating direct antiviral activity against both HBV and the hepatitis D virus (HDV).

It is the first siRNA to enter clinical trials that employs enhanced stability chemical modification technology to improve stability and minimize off-target activity, thereby potentially increasing the therapeutic index.

Clinical studies have demonstrated that VIR-2218, either as monotherapy or in combination regimens, can significantly reduce HBsAg levels, laying the foundation for a functional cure of hepatitis B. The drug is currently undergoing multiple Phase II clinical trials to explore combination strategies with immunomodulators such as PEG-IFNα and TLR8 agonists, aiming to achieve HBsAg clearance through a dual strategy of “reducing antigen load + restoring immune response.”

However, the drug’s market approval was not as smooth as anticipated, and Brii Biosciences believes that the future prospects of the elebsiran project remain uncertain.

The progress of the elebsiran project has been impacted by a dispute with partner company Vir. According to the announcement by Brii Biosciences, as early as 2018, Brii Biosciences entered into a collaboration with Vir Biotechnology of the United States. Under this agreement, each party may exercise an option to obtain an exclusive license to advance the development and commercialization of certain products initially developed by the other party.

In 2020, Brii Biosciences exercised its option for the elebsiran candidate drug. On December 19, 2024, Brii Biosciences and Vir signed a sixth letter agreement to transfer the manufacturing of the drug product from Vir to Brii Biosciences.

The Turning Point in April 2026: Brii Biosciences Accuses Vir of Breaching the Collaboration Agreement and Letter Agreement, Files for Arbitration Against Vir with JAMS, Seeking to Transfer the Production of Elebsiran to Brii Biosciences or Its Contractors and Claim Corresponding Compensation。The arbitration is still in its early stages, and Brii Biosciences and Vir have not yet reached a settlement regarding the claims.

The progress of the elebsiran project will be affected, with Brii Biosciences stating that the future prospects of the elebsiran project are uncertain. Unless and until the claims in arbitration are resolved satisfactorily, Brii Biosciences will be unable to invest in conducting any Phase III clinical studies on hepatitis B combination therapies containing elebsiran. The future market launch of elebsiran in China is uncertain.

In the field of clinical cure for hepatitis B, capsid protein allosteric modulators (CpAMs) represent a key area of research and development, with Guangshengtang’s Nerikove (GST-HG141) garnering significant attention. As a small-molecule oral drug, GST-HG141 targets the viral capsid assembly process. It not only significantly inhibits HBV DNA replication but also reduces HBV pgRNA levels, thereby potentially suppressing and depleting cccDNA, the root cause of persistent viral infection. Currently, its Phase III clinical trial has completed enrollment of all subjects, focusing on patients who have had a suboptimal response to antiviral therapy.

Based on the published Phase II data, GST-HG141 has demonstrated excellent virologic suppression in patients with low-level viremia—achieving an HBV DNA complete response rate of over 80% and a pgRNA suppression rate of over 55%—but the reduction in HBsAg levels was limited. This suggests that GST-HG141 monotherapy is insufficient to achieve clinical cure, and combination therapy with immunomodulators or agents targeting other pathways is essential.

To this end, Guangshengtang proposed the “Peak Climbing Plan” clinical cure roadmap as early as 2015: centered on GST-HG141 to deplete cccDNA, combined with GST-HG131/GST-HG121 to inhibit HBsAg secretion, and supplemented by nucleos(t)ide analogues to maintain virological suppression, thereby launching an assault on clinical cure through multi-target synergy. Currently, this triple-drug regimen is in the early stages of clinical exploration.

It is evident that drugs for the clinical cure of hepatitis B are entering a period of transformation, with multiple technological approaches advancing in parallel, all holding the promise of breakthrough changes. In the next five years, the clinical cure rate for hepatitis B could reach 30%–50%, and the development of diverse technological pathways, along with the application of combination therapies, has the potential to further significantly increase the cure rate.

References:

Investment Opportunities Amid the Drive to Eliminate Viral Hepatitis: Bullish on Companies Pursuing Functional Cure for Hepatitis B — Western Securities

Expert Forum | Chinese Practice, Treatment Strategies, and Prospects for Clinical Cure of Chronic Hepatitis B—Chinese Journal of Hepatology

Did the Launch of New Hepatitis B Cure Drug 836 Fail? — Dr. Hu Zhaoxia