Race for Hepatitis B Functional Cure Reaches Decisive Phase, First Approvals Expected by 2027

The Long-Distance Race for Clinical Cure of Hepatitis B Is About to Cross the Finish Line. Several Chinese Faces Are Present in This Historic, Milestone-Level Breakthrough in New Drug Development.

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

The 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 at Nanfang Hospital, Southern Medical University, is the Core Principal Investigator (Core PI) of this study, and the related research findings have been published 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 features not only overseas companies, but also multiple domestic enterprises that have 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 liver cancer. The severe situation in China, characterized by persistently high incidence rates of liver cancer, has made achieving a clinical cure an urgent priority.

Bottlenecks and Technical Roadmap for the Clinical Cure of Hepatitis B

Hepatitis B is the most prevalent chronic viral infection worldwide, with over 240 million people living with chronic hepatitis B (CHB) globally. 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 its label as a country with a high burden of hepatitis B, the proportion of hepatocellular carcinoma and liver cirrhosis caused by hepatitis B remains high.The situation is severe. According to data from Brii Biosciences' prospectus, globally, the proportions of patients with primary liver cancer and cirrhosis caused by HBV infection are 45% and 30%, respectively. In China, the proportions of patients with primary liver cancer and cirrhosis caused by HBV infection are 80% and 60%, respectively.

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, the hepatitis B virus (HBV) produces substantial amounts of circulating surface antigens and other proteins. These HBV products exhibit immunosuppressive properties; sustained high levels of hepatitis B surface antigen (HBsAg) lead to T-cell exhaustion and impaired immune responses. This constitutes a major reason why chronic hepatitis B (CHB) is difficult to cure.

Current nucleos(t)ide analogs intervene at the late stage of 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 there is a risk of drug resistance, making it difficult to achieve HBsAg clearance.

Another class of drugs, long-acting interferons, possesses both antiviral and immune-activating effects and can achieve clinical cure in some patients; however, they are limited by a small proportion of responders, a prolonged treatment course, and significant side effects.

Therefore, achieving a clinical cure for hepatitis B has become the holy grail in the global pursuit of novel hepatitis B therapeutics. 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 proportion of patients in China still attempt to use it as a potential functional therapy.

To achieve a clinical cure for hepatitis B, companies worldwide have explored multiple approaches.Pathway 1: Striking at the viral reservoir by targeting the HBV life cycle.From the moment the virus enters hepatocytes, every step—including replication, assembly, and release—is targeted by novel therapeutic agents. These include entry inhibitors, cccDNA inhibitors, RNA interference therapies (small interfering RNA [siRNA] and 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, 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 efficacy in reducing HBsAg levels.

Furthermore, as 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, this implies that achieving a high-efficacy cure for hepatitis B will necessarily 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 to 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 investigational pipelines for hepatitis B cure worldwide; VBDATA has compiled the five most noteworthy late-stage clinical pipelines.

■ GSK Bepirovirsen: The first new hepatitis B drug expected to launch as early as 2027

Bepirovirsen (Bepirovirsen Injection) is undoubtedly the most closely 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.

CTTQ Recognizes the Sales Potential of Bepirovirsen in the Chinese Market and Secures Its Commercialization Rights in China Through a Partnership with GSK in May 2026.

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, and creates a window for immune system recovery, thereby enhancing 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, reaching the primary endpoint.

Regarding 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 to gain approval in the United States will be the focus of industry attention.

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

Industry insiders revealed that the initial application was not rejected due to issues with efficacy, safety, or data, but rather due to a system error. 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.

■ AusperBio AHB-137: A Promising Domestic ASO Drug Candidate

In the race for antisense oligonucleotide (ASO) drugs targeting hepatitis B, Bepirovirsen is not the sole contender; Chinese-developed pipelines are also highly competitive. Among the three ASO candidates 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 Hangzhou AusperBio.

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, the final follow-up data from the Phase II clinical trial of AHB-137 in treatment-naïve chronic hepatitis B patients (without nucleos(t)ide analogue background therapy) were first presented 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 sustained long-term 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).

An industry insider 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 global Phase I clinical trials and is currently advancing multiple global Phase II clinical trials as well as a Phase III clinical trial in China.

■ Hengrui Pharma HRS-5635: The First siRNA Drug for Hepatitis B Clinical Cure to Enter Phase III Trials

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.

New siRNA Drugs for the Clinical Cure of Hepatitis B Take Effect Faster and Require Less Frequent Dosing Than ASO Drugs; However, More Clinical Data Are Needed to Substantiate Their Efficacy.

Johnson & Johnson, Hengrui Pharma, Qilu Pharmaceutical, Ribo Life Science, Bowang Pharma, Chia Tai Tianqing, and Xingyao Kunze, among other companies, are developing siRNA drugs for hepatitis B treatment. Among them, Hengrui Pharma’s HRS-5635 has advanced to Phase III clinical 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) double-stranded small interfering RNA that can selectively deliver into liver cells through the binding of GalNAc to the asialoglycoprotein receptor (ASGPR) on the surface of hepatocytes. 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 indicate that HRS-5635 has the potential to improve clinical cure rates for chronic hepatitis B, while also demonstrating a favorable safety profile, and is expected to provide more treatment options for patients with chronic hepatitis B.

The R&D direction of siRNA drugs is mainly focused on combination therapy. The Phase II study of Hengrui Pharma's HRS-5635 in combination with PEG-IFNα for the treatment of chronic hepatitis B is currently ongoing.

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.

■ Brii Biosciences elebsiran: siRNA utilizing chemical enhancement technology

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

Elebsiran is an investigational small interfering ribonucleic acid (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 utilizes enhanced stability chemical modification technology to enhance stability and minimize off-target activity, thereby potentially improving 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. Currently, the drug is 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 are uncertain.

The progress of the elebsiran project has been impacted by a dispute with partner company Vir.. According to Brii Biosciences' announcement, as early as 2018, Brii Biosciences entered into a collaboration with U.S.-based Vir Biotechnology. Under the agreement, each party holds 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 came in April 2026, when Brii Biosciences accused Vir of violating the collaboration agreement and related letters, and filed for arbitration against Vir with the American Arbitration Association (AAA), demanding that the production of elebsiran be transferred to Brii Biosciences or its contractors, as well as payment of 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, and Brii Biosciences stated that the future prospects of the elebsiran project are uncertain. Unless and until the claims in arbitration are satisfactorily resolved, Brii Biosciences will not be able to invest in conducting any Phase III clinical studies on hepatitis B combination therapies involving elebsiran. The future market launch of elebsiran in China is uncertain.

■ Guangshengtang Nairikewe (GST-HG141) Small-Molecule Oral Drug

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 Nerikewei (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 drug therapy.

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

To this end, as early as 2015, Guangshengtang proposed the “Summit Plan” roadmap for clinical cure: centered on GST-HG141 to deplete cccDNA, combined with GST-HG131/GST-HG121 to inhibit HBsAg secretion, and supplemented by nucleos(t)ide analogs to maintain virological suppression, thereby launching an assault on clinical cure through multi-target synergy. Currently, this triple-drug regimen is in the early stage 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 promise for breakthrough innovations. Over 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, may 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 | Clinical Cure of Chronic Hepatitis B: Chinese Practice, Treatment Strategies, and Prospects—Chinese Journal of Hepatology

Has the Launch of New Hepatitis B Cure Drug 836 Failed? — Dr. Hu Zhaoxia

This article is from the WeChat official account“Arterial Network” (ID: vcbeat), Author: Yang Xue, published by 36Kr with authorization.