Advancing Toward Hepatitis B Cure: Latest Clinical Progress in RNA Therapies, Cell Therapies, and Beyond

Currently,There is currently no complete cure for hepatitis B.. The core goal of hepatitis B drug development is to create new drugs that can achieve "functional cure" or even "complete cure."

Recently, SCG SCIENCE (DALIAN) CO., LTD（SCG）Announcement from the Center for Drug Evaluation of the National Medical Products Administration（NMPA）Has been approved for its investigational new drug for hepatitis B SCG101V1/2 Phase Clinical Trial Application. It is reported that this candidate drug isThe World's First TCR-T Cell Therapy Product for Chronic Hepatitis B。

SCG101V is an innovative TCR-T cell therapy developed by SCG SCIENCE (DALIAN) CO., LTD based on its GianTCR™ technology platform. It is mediated by specific TCRs, which can selectively identify and target stem cells infected with the hepatitis B virus through multiple mechanisms.Clear cccDNA(Covalently Closed Circular DNA)And eliminate viral reservoirs and integrated fragments, establishing protective immune memoryOnce the viral reservoir is completely eliminated, HBV has no way to rebound.

In terms of clinical data, SCG101V has demonstrated revolutionary "curative" potential, capable of simultaneously eliminating hepatitis B cccDNA and HBsAg with just a single dose.

China's "Guidelines for the Prevention and Treatment of Chronic Hepatitis B" clearly states that functional cure should be pursued for some eligible patients with chronic hepatitis B.(Clinical Cure)。

HBsAg is the envelope protein of mature hepatitis B virus, and its serological level has a dual biological significance. The HBsAg in serum mainly originates from the transcription and translation process of cccDNA within hepatocytes, where,cccDNA is the core reason for HBV replication, persistent infection, and relapse., with high stability and sustainability; it is also closely related to HBV DNA integrated into the host genome, especially in HBeAg-negative patients.

Therefore, HBsAg not only reflects the transcriptional activity of cccDNA but also indicates the control status of the body's immune system over the virus, serving as a key indicator for evaluating immune responses.

Previously, the main treatment goal for chronic hepatitis B was through nucleoside(Acid)Analogs effectively control viral load. With the continuous advancement of medical technology, an increasing number of innovative therapies are emerging, making the clearance of hepatitis B surface antigen and achieving a cure the new treatment goal.

At this stage, the cure goals for hepatitis B are divided into two major levels.Functional cure refers to the clearance of HBsAg, while complete cure requires the total elimination of cccDNA and integrated HBV DNA within hepatocytes.。

According to incomplete statistics, there are over 200 new hepatitis B drugs currently under research globally, which can be mainly divided by mechanism of action into"Direct-acting Antiviral Drugs"And"Indirect Antiviral Drugs"Two major categories, the formerTargeting the HBV life cycle, the latterTargeting the Host Immune System。

▲ Source of the image:Journal of Clinical Hepatobiliary Diseases - Yulu Ganlin

Direct-acting antiviral agents, due to their more direct viral suppression characteristics, play a dominant role in new drug development, with technology pathways coveringSmall interfering RNA（siRNA）、Antisense oligonucleotide（ASO）, Gene Editing, Capsid InhibitorsIn multiple fields such as .

The following is a brief introduction to the two types of small nucleic acid therapies, siRNA and ASO. In terms of mechanism of action, both inhibit viral protein expression by degrading HBV mRNA, but the specific pathways may vary.

Studies have shown that siRNA drugs can inhibit HBsAg derived from integrated HBV DNA and cccDNA, but have no direct effect on cccDNA or integrated viral DNA; ASOs mainly bind to HBV mRNA through sequence complementarity, directly blocking ribosomal recognition of viral mRNA and inhibiting the translation process of key viral proteins such as HBsAg and HBeAg.

Currently, the fastest clinical progress is an ASO drug jointly developed by GSK/lonis.Bepirovirsen, the drug is alsoThe earliest and only one to enter Phase 3A new hepatitis B drug in the clinical stage. According to GSK's 2024 financial report, this candidate drug will be submitted for marketing approval in the United States, the European Union, China, and Japan in 2026.

In the early phase 2b clinical trial,Approximately 30% of patients achieved HBsAg seroclearance after 24 weeks of treatment. At 24 weeks post-treatment, over 10% of patients maintained this clearance effect., and there are no significant side effects.

In the siRNA field,Elebsiran It is one of the fastest-progressing candidate drugs, currently in Phase 2 clinical trials, co-developed by Vir Biotechnology and Alnylam Pharmaceuticals. In 2020, Brii Biosciences acquired exclusive rights to the drug in the Greater China region from Vir Biotechnology.

At the 2025 APASL Annual Meeting, Brii Biosciences announced Elebsiran + Pegylated Interferon Alpha（PEG-IFNα）New Data from Phase 2 ENSURE Study in Chronic Hepatitis B Patients Treated with Combination Therapy.

Week 48 endpoint data shows,Patients receiving 200 mg or 100 mg Elebsiran combined with PEG-IFNα treatment achieved HBsAg seroclearance rates of26.3% and 33.3%，significantly higher than the PEG-IFNα monotherapy cohort（5.6%）Overall, the combination therapy of elebsiran and PEG-IFNα was safe and well-tolerated, demonstrating similar effects in terms of HBsAg reduction and seroclearance rates.

Moreover, for patients who had previously received the therapeutic hepatitis B vaccine BRII-179 and developed an antibody response, the HBsAg clearance rate of the aforementioned combination therapy increased from 10% in non-responders to 55.6%。

In China, multiple companies have made substantial progress in the development of innovative hepatitis B drugs, covering not only small nucleic acid drugs represented by ASO and siRNA but also extending to the field of cell therapy.

In the ASO field,Haobo MedicineThe AHB-137 under research has shown particularly outstanding results. The Phase 2b data presented at the 2025 EASL Annual Meeting revealed,Patients receiving 300 mg dose group treatment for 24 weeks75% HBsAg Turned NegativeAnd HBV DNA is below the detection limit.; In the 16-week treatment group, 66% of patients reached this primary endpoint. Among the two treatment groups, 54% and 33% of participants respectively achieved seroconversion of hepatitis B surface antibodies.

Previously, based on the significant advantages demonstrated by early Phase 1/2a clinical data, AHB-137 was granted Breakthrough Therapy Designation by the CDE in July 2024. The positive efficacy and favorable safety data from this Phase 2b trial highlight AHB-137's tremendous potential in achieving clinical cure for hepatitis B. Based on these encouraging results, Haobo Medicine successfully completed a $50 million Series B+ financing round at the end of May this year to accelerate the international multicenter clinical trials and early commercialization preparations for AHB-137.

In the siRNA field, companies in China also stand out. BW-20507 isBowang PharmaceuticalBW-20507, a GalNAc-conjugated siRNA drug developed by SCG SCIENCE (DALIAN) CO., LTD, targets the S region of mRNA. The latest published Phase 1/2 clinical trial data shows that subcutaneous injection of BW-20507 significantly reduces HBsAg levels in a dose-dependent manner, with the maximum reduction observed at doses of 200 mg and 400 mg being 2.9~3.2 log10 IU/mL.In subjects with baseline HBsAg levels below 1000 IU/mL,56% Achieved HBsAg Clearance During the Study Period。

According to the official press release, based on the positive results obtained, Bowang Pharmaceutical plans to initiate a Phase 2b clinical trial this year. On June 11, BW-20507 was designated as a breakthrough therapy. On July 1, the combination therapy of BW-20507 + PEG-IFNα was approved by the CDE for Phase 2 clinical trials. Preclinical and early clinical data have shown that this combination therapy can significantly improve HBsAg clearance rates.

HT-101 is the first Chinese-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.

PreviouslyStellar KunzeThe published Phase 1b clinical study showed that all subjects in the HT-101 treatment group who participated in the extension phase maintained a good reduction in HBsAg levels at 48 weeks. Notably, in the 400 mg dose group,One subject achieved HBsAg clearance after 48 weeks of follow-up post two-dose vaccination.。

In addition to the aforementioned pipelines, there are multiple small nucleic acid pipelines under research in China for the treatment of chronic hepatitis B, such asRibo Biotech's RBD1016, CT Tianqing's TQA3038, Hengrui Pharma's HRS-5635Etc.

Despite the significant efficacy of small nucleic acid drugs such as ASO and siRNA in HBsAg suppression, their inability to directly eliminate the viral replication template cccDNA and integrated viral genome remains a limitation. Hepatitis B virus cccDNA can integrate into human DNA, interfering with proto-oncogenes, tumor suppressor genes, and genomic stability, leading to uncontrolled proliferation of hepatocytes and directly inducing carcinogenesis. This is also a key obstacle for existing therapies to achieve complete cure.

Against this backdrop, cell therapy offers a new approach for clearing cccDNA, establishing long-term immune memory, and even curing hepatitis B by activating or reshaping the immune system.

SCG SCIENCESCG101V, a TCR-T therapy, has recently been approved for clinical trials, becoming the world's first cell therapy product targeting chronic hepatitis B. Its core mechanism involves genetically engineering the patient's autologous T cells. The modified T cells can selectively identify and target HBV-infected hepatocytes, eliminating cccDNA and eradicating viral reservoirs and integrated fragments through multiple mechanisms while establishing protective immune memory.

In addition to SCG SCIENCE (DALIAN) CO., LTD's TCR-T therapy, global research teams are also exploring various other cell therapies for hepatitis B treatment. For instance, a 2020 study demonstrated that HBsAg-specific CAR-T cells exhibited antiviral activity in vitro and in mouse models, but their safety and efficacy still require further validation.

With the rapid development of various innovative therapies, the path to functional cure for hepatitis B is becoming increasingly clear. From the current R&D trend, the combination of innovative therapies with different mechanisms of action is expected to become the mainstream treatment strategy in the future.

Editor-in-Chief | Luca

Proofread by Luca

References:

1.Corporate Official Website

2.Zhang Jiming. Current Status and Challenges of HBV cccDNA Research[J]. Journal of Clinical Hepatology, 2019, 35(6): 1177-1180.

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