Bepirovirsen Approved: Chronic Hepatitis B Treatment Moves from Long-Term Viral Suppression Toward Functional Cure
Bepirovirsen Approved: Chronic Hepatitis B Treatment Moves from Long-Term Viral Suppression Toward Functional Cure
Introduction
On August 24, 2026, Japan’s Ministry of Health, Labour and Welfare approved bepirovirsen (development code GSK3228836, commonly abbreviated as GSK836), developed by GSK and marketed under the brand name Hibsago, for functional cure in eligible adults with persistent hepatitis B virus infection. This was the first regulatory approval of bepirovirsen worldwide and marked an important milestone in functional cure therapy for chronic hepatitis B.[1]
The breakthrough represented by bepirovirsen does not mean that hepatitis B virus can now be completely eradicated from the human body. Rather, it changes the long-standing treatment paradigm for chronic hepatitis B, which has primarily focused on the continuous suppression of viral replication: after a finite course of treatment, a proportion of selected patients can discontinue all antiviral therapy while maintaining hepatitis B surface antigen loss and sustained control of viral DNA, thereby achieving what is clinically termed a “functional cure.”[1,2]
Two Phase III clinical trials showed that, in the primary analysis population with baseline hepatitis B surface antigen levels of no more than 3,000 IU/mL, the functional cure rate after bepirovirsen treatment was 19%; among patients with baseline surface antigen levels of no more than 1,000 IU/mL, this proportion increased to 26%.[2]
1. From Viral Suppression to Functional Cure: How Has the Treatment Goal Changed?
Current first-line antiviral drugs for chronic hepatitis B include nucleos(t)ide analogues such as entecavir and tenofovir. These agents can potently suppress hepatitis B virus replication, reduce circulating viral DNA to very low levels, and substantially lower the risks of hepatitis activity and disease progression.
However, suppression of viral DNA during treatment does not mean that the body can independently control the infection once treatment is withdrawn. Many patients require long-term continuous therapy, and hepatitis B surface antigen loss remains uncommon.
Functional cure advances the treatment goal further. In the Phase III trials of bepirovirsen, after completion of the fixed treatment course and discontinuation of all therapy, patients were required to maintain the following for at least 24 weeks:
① Loss of hepatitis B surface antigen (HBsAg);
② Sustained hepatitis B virus (HBV) DNA levels below the lower limit of quantification.[2]
Achieving this state indicates that the infection remains controlled even in the absence of continued antiviral treatment.
Functional cure does not require complete elimination of all hepatitis B virus genetic material from the body. Viral covalently closed circular DNA (cccDNA) may remain in the nuclei of hepatocytes, and some viral DNA may also have become integrated into the host chromosome. Functional cure therefore represents a state of sustained virological and host control rather than a “sterilizing cure” in which viral genetic material is completely eliminated.[5,6]
2. Why Can Hepatitis B Be Suppressed for the Long Term Yet Remain Difficult to Control After Treatment Withdrawal?
After hepatitis B virus enters hepatocytes, it forms covalently closed circular DNA in the nucleus. This relatively stable viral genetic template can continuously generate viral RNA through transcription.
Hepatitis B virus produces multiple RNA transcripts. Viral proteins such as surface antigen are translated from the corresponding viral RNAs. Among them, pregenomic RNA (pgRNA) has a dual function: it serves both as a template for translation of the viral core protein and polymerase and as the template for reverse transcription to generate new viral DNA.
The viral replication process can be simplified as:
Viral DNA template → viral RNA → viral proteins
At the same time:
Pregenomic RNA → reverse transcription → new viral DNA
Nucleos(t)ide analogues such as entecavir and tenofovir primarily inhibit reverse transcription in the latter pathway. They can therefore efficiently block the formation of new viral DNA, but they do not directly eliminate covalently closed circular DNA and cannot completely prevent the production of all viral RNAs and surface antigen.
Chronic hepatitis B also has another important source of viral antigen. Some hepatitis B virus DNA can integrate into the chromosomes of host hepatocytes. Integrated viral DNA generally cannot independently complete the full viral replication cycle, but some of its sequences can remain transcriptionally active and continue to produce hepatitis B surface antigen.[5,6]
In studies of liver tissue from HBV/HIV-coinfected individuals receiving nucleos(t)ide analogue therapy, transcription of hepatitis B surface antigen from covalently closed circular DNA decreased with increasing treatment duration, whereas the relative contribution of transcription from integrated HBV DNA increased.[5,6]
These findings provide an important mechanistic explanation for a common phenomenon in chronic hepatitis B treatment: “viral DNA has been suppressed for a prolonged period, yet hepatitis B surface antigen persists.”
Persistent viral antigens are also closely associated with impaired hepatitis B virus-specific immune responses. Further reducing viral RNA and antigen burden has therefore become an important therapeutic direction for advancing from long-term viral suppression toward functional cure.
3. How Bepirovirsen Works: Moving the Intervention Point Upstream to Viral RNA
Bepirovirsen is an antisense oligonucleotide (ASO) drug.
An antisense oligonucleotide is a designed short nucleic acid sequence that recognizes a specific RNA through complementary base pairing. The target sequence recognized by bepirovirsen is present in multiple hepatitis B virus messenger RNAs and pregenomic RNA, allowing the drug to affect both viral protein production and viral RNAs involved in replication.[3]
Its mechanism of action can be summarized as follows:
Bepirovirsen recognizes hepatitis B virus RNA
→ Forms a nucleic acid hybrid with the target RNA
→ Recruits endogenous cellular ribonuclease H (RNase H)
→ The target viral RNA is cleaved and degraded
The reduction in viral RNA produces two major effects:
Reduced viral messenger RNA
→ Reduced hepatitis B surface antigen and other viral proteins
and:
Reduced pregenomic RNA
→ Reduced template available for reverse transcription
→ Further suppression of viral DNA replication.[3]
Compared with nucleos(t)ide analogues, which primarily act at the viral reverse-transcription stage, bepirovirsen moves antiviral intervention upstream to the viral RNA level and can therefore affect both viral replication and viral antigen production.
Bepirovirsen also has innate immune-stimulatory activity. A 2026 mechanistic study showed activation of multiple inflammatory cytokines and immune-related pathways following administration, while cellular and animal experiments indicated that Toll-like receptor 8 (TLR8) is involved in at least part of these immune effects.[7]
This immunomodulatory activity coexists with the established viral RNA-degradation mechanism of bepirovirsen, but its precise contribution to the eventual achievement of functional cure in patients has not yet been fully determined.[7]
Early Phase II clinical studies observed virological changes in patients that were consistent with the mechanism of action of bepirovirsen. Among patients who were not receiving nucleos(t)ide analogue therapy at study initiation, four weeks of bepirovirsen treatment produced dose-related reductions in hepatitis B surface antigen and hepatitis B virus DNA, with the most pronounced reductions at Day 29 in the 300 mg group. These patients had not yet started subsequent nucleos(t)ide analogue therapy, meaning that changes before Day 29 could reflect the early treatment effect of bepirovirsen itself.[3]
As shown in Figure 1, some patients in the 300 mg group experienced marked reductions in hepatitis B surface antigen; marked surface antigen reductions were also observed in some patients in the 300 mg group who were already receiving stable nucleos(t)ide analogue therapy at study initiation. These early findings provided clinical evidence in humans that bepirovirsen can affect both viral antigen levels and viral replication.[3]
Figure 1. Changes in serum hepatitis B surface antigen and hepatitis B virus DNA after bepirovirsen treatment.
Panel a shows changes in serum hepatitis B surface antigen, and panel b shows changes in serum hepatitis B virus DNA. The three groups on the left comprised patients who were not receiving nucleos(t)ide analogue therapy at study initiation and who received placebo, bepirovirsen 150 mg, or bepirovirsen 300 mg, respectively. The two groups on the right comprised patients who were receiving stable nucleos(t)ide analogue therapy at study initiation and who received placebo or bepirovirsen 300 mg, respectively. Blue lines represent hepatitis B e antigen (HBeAg)-positive patients, and gray lines represent HBeAg-negative patients; the black horizontal dashed line indicates the lower limit of quantification, and the gray shaded area indicates the nucleos(t)ide analogue treatment period. For patients who were not receiving nucleos(t)ide analogue therapy at study initiation, nucleos(t)ide analogue therapy was initiated after completion of the virological assessment on Day 29.[3]
Image source: Yuen MF, Heo J, Jang JW, et al. Nature Medicine. 2021;27:1725–1734, Figure 1. Licensed under CC BY 4.0.
The subsequent Phase IIb B-Clear study further evaluated sustained treatment effects after a longer course of therapy. In the group receiving bepirovirsen 300 mg once weekly for 24 consecutive weeks, approximately 10% of patients achieved the primary endpoint regardless of whether they were receiving nucleos(t)ide analogue therapy at study initiation. Specifically, the rate was 9% (6/68) among patients receiving nucleos(t)ide analogue therapy and 10% (7/70) among those who were not; the results were similar between the two groups. The endpoint required hepatitis B surface antigen to remain below the limit of detection and hepatitis B virus DNA to remain below the lower limit of quantification for 24 weeks after the planned end of bepirovirsen treatment, without initiation of new antiviral therapy to suppress hepatitis B virus replication during that period.[4]
4. Phase III Studies: What Do Functional Cure Rates of 19% and 26% Mean?
The key clinical evidence for bepirovirsen comes from two identically designed global Phase III studies—the B-Well 1 and B-Well 2 trials. Both were randomized, double-blind, placebo-controlled trials conducted across 29 countries worldwide.[2]
The studies enrolled adults with chronic hepatitis B who had no cirrhosis and were receiving stable nucleos(t)ide analogue therapy, with hepatitis B surface antigen levels above 100 and no more than 3,000 IU/mL at enrollment. Participants were randomized in a 2:1 ratio to receive subcutaneous bepirovirsen 300 mg or placebo once weekly for 24 weeks while continuing their existing nucleos(t)ide analogue therapy.[2]
After completion of the 24-week bepirovirsen or placebo treatment period, patients continued their existing nucleos(t)ide analogue therapy. Those meeting treatment-withdrawal criteria discontinued the nucleos(t)ide analogue at Week 48 and were assessed for functional cure at Week 72. In other words, the primary assessment was whether patients could maintain hepatitis B surface antigen loss and hepatitis B virus DNA below the lower limit of quantification for 24 weeks after discontinuing all treatment.[2]
Results were highly consistent between the two studies: in B-Well 1, 20% of patients in the bepirovirsen group achieved functional cure; in B-Well 2, the rate was 19%. The rate was 0% in both placebo groups.[2]
Patient Population | Bepirovirsen Group | Placebo Group |
Baseline hepatitis B surface antigen ≤3,000 IU/mL | 19% (233/1,220) | 0% (0/614) |
Baseline hepatitis B surface antigen ≤1,000 IU/mL | 26% (200/768) | 0% (0/393) |
The 19% figure represents the overall result in the primary analysis population of the two studies. Among patients with lower pretreatment hepatitis B surface antigen levels—no more than 1,000 IU/mL—the proportion achieving functional cure increased further to 26%. These findings suggest that lower pretreatment surface antigen levels can enrich for a population with a higher probability of functional cure and represent an important parameter for patient stratification.[2]
The 0% rate in the placebo groups represents only the observation made under the specified patient eligibility criteria, treatment regimens, and follow-up period of these two Phase III studies. A small proportion of patients receiving long-term nucleos(t)ide analogue therapy can still achieve hepatitis B surface antigen loss, so the 0% result should not be interpreted as meaning that conventional treatment can never result in functional cure under any circumstances.
Safety
The pooled safety analysis of the two Phase III trials showed that during Weeks 1–24 of treatment, at least one adverse event was reported in 89% of patients in the bepirovirsen group and 65% of those in the placebo group. The most common adverse events in the bepirovirsen group were injection-site erythema (31%), injection-site pain (23%), and transient elevations in alanine aminotransferase (22%). Injection-site reactions were generally mild, and no severe injection-site reactions were reported in the studies.[2]
During treatment, Grade 3 or higher adverse events occurred in 16% of patients in the bepirovirsen group and 3% of those in the placebo group. The most common Grade 3 adverse event in the bepirovirsen group was elevated alanine aminotransferase (ALT), occurring in 6% of patients. Through Week 72 of follow-up, serious adverse events occurred in 7% and 4% of patients in the two groups, respectively.[2]
The studies observed that transient elevations in alanine aminotransferase after initiation of bepirovirsen treatment were associated with reductions in hepatitis B surface antigen, suggesting that some of these changes may occur concurrently with treatment response. However, elevations in alanine aminotransferase still reflect hepatocellular injury or inflammatory activity and therefore require clinical interpretation and monitoring in conjunction with hepatitis B surface antigen, viral DNA, other liver function parameters, and the patient’s clinical condition.[2]
5. Which Patients Currently Show a Higher Probability of Functional Cure?
The Phase III studies suggest that lower baseline hepatitis B surface antigen levels can enrich for patients with a higher probability of response. A baseline surface antigen level of ≤1,000 IU/mL is currently a relatively well-defined response-enrichment marker, but it is not a cutoff that can definitively predict whether an individual patient will achieve functional cure.[2]
The patient criteria used for the approval in Japan further reflect the current clinical positioning of bepirovirsen. Before starting treatment, patients are required to:
① Have received nucleos(t)ide analogue therapy for at least 6 months;
② Have hepatitis B surface antigen ≤3,000 IU/mL;
③ Have hepatitis B virus DNA <90 IU/mL.[1]
Bepirovirsen is currently used primarily in patients whose viral replication has already been well controlled by nucleos(t)ide analogue therapy, with the aim of advancing further toward functional cure.
The pivotal Phase III studies enrolled adults without cirrhosis. Therefore, the 19% and 26% results cannot be directly extrapolated to patients with cirrhosis, decompensated liver disease, or other populations not adequately represented in the pivotal studies.[2]
Chinese Patient Subgroup
Regional subgroup data from the Phase III studies released by GSK showed that:
① Among Chinese participants with baseline surface antigen ≤3,000 IU/mL, the functional cure rate was 24%;
② Among Chinese participants with baseline surface antigen ≤1,000 IU/mL, the functional cure rate was 35%.[8]
These results indicate a signal of higher treatment response among Chinese participants, but they derive from a regional subgroup analysis and the 35% figure cannot be extrapolated as the overall functional cure rate for the Chinese chronic hepatitis B population. Differences in baseline characteristics, viral genotypes, antigen levels, and sample size across regions may all affect subgroup results.
6. Compared with Existing Treatments, Where Does the Real Breakthrough of Bepirovirsen Lie?
Bepirovirsen is not intended simply to replace nucleos(t)ide analogues such as entecavir and tenofovir. Instead, it targets another long-standing challenge in chronic hepatitis B treatment—viral RNA and persistent viral antigens.
Treatment | Primary Action | Treatment Characteristics | Major Limitations |
Nucleos(t)ide analogues such as entecavir and tenofovir | Inhibit viral reverse transcription and DNA replication | Oral administration, potent viral suppression, extensive long-term clinical experience | Surface antigen clearance is uncommon, and many patients require long-term treatment |
Pegylated interferon | Has both antiviral and immunomodulatory effects | Finite treatment course; some patients can achieve surface antigen loss | Limited by patient eligibility and tolerability |
Bepirovirsen | Targets hepatitis B virus RNA, reduces viral antigens and replication-related RNA, and is accompanied by innate immune stimulation | Fixed treatment course; can enable some selected patients to achieve functional cure after treatment withdrawal | Requires subcutaneous injection; most patients currently do not achieve functional cure, and patient selection is required |
The breakthrough achieved with bepirovirsen is mainly reflected in three areas.
① Extending treatment from viral DNA replication to viral RNA and antigen production
Conventional nucleos(t)ide analogues can already suppress viral DNA replication very effectively. Bepirovirsen additionally acts directly on viral RNA, reducing both viral surface antigen and pregenomic RNA involved in replication.[3]
② Advancing from long-term maintenance therapy to sustained control after a finite treatment course
After 24 weeks of bepirovirsen treatment, some eligible patients were ultimately able to discontinue all antiviral therapy and maintain functional cure for at least 24 weeks.[2]
This demonstrates that, in some patients, chronic hepatitis B treatment can progress from “continuous drug-mediated suppression of the virus” to “host-maintained viral control after treatment withdrawal.”
③ Functional cure becomes a treatment goal validated in Phase III trials and translated into regulatory approval
Hepatitis B surface antigen loss and functional cure have long been important goals of chronic hepatitis B research. The approval in Japan links this goal for the first time to a regulatory-approved, finite-course treatment with a new mechanism of action.[1]
At the same time, bepirovirsen still has clear limitations:
① The overall functional cure rate is 19%, meaning that most patients do not currently reach this endpoint;
② It does not directly eliminate all covalently closed circular DNA or integrated viral DNA;
③ Current pivotal Phase III evidence comes mainly from selected adults who were already receiving nucleos(t)ide analogue therapy and did not have cirrhosis;
④ Lower baseline surface antigen levels can enrich for patients with a higher probability of response, but it remains impossible to accurately predict whether an individual patient will definitely achieve functional cure.
One important direction for future research is the sequential or combined use of therapies with different mechanisms—for example, first further reducing viral RNA and antigen burden, followed by immunomodulatory or other therapeutic approaches to increase the probability of sustained viral control.
7. Where Does Regulatory Review Stand in China, and When Might Bepirovirsen Become Available Domestically?
Bepirovirsen has not yet received formal approval from China’s National Medical Products Administration, but its Chinese registration has entered the marketing authorization review stage.
In August 2021, bepirovirsen was included in the Breakthrough Therapy Designation program of the Center for Drug Evaluation under China’s National Medical Products Administration.[9]
In March 2026, China’s National Medical Products Administration formally accepted its New Drug Application for marketing authorization.[10]
In April 2026, bepirovirsen was further included in the Priority Review and Approval program.[9]
In May 2026, GSK entered into an exclusive strategic collaboration with Chia Tai Tianqing, a subsidiary of Sino Biopharmaceutical. According to public information from the two companies, Chia Tai Tianqing will be responsible for the future importation, distribution, and hospital access of bepirovirsen in mainland China, while GSK will continue to assume the relevant responsibilities of the marketing authorization holder.[9]
On May 28, 2026, Sino Biopharmaceutical announced that GSK expects to receive a regulatory decision from China’s National Medical Products Administration in the first half of 2027.[11]
This timing represents GSK’s expectation based on the current review progress and is not a regulatory approval date already determined by the National Medical Products Administration.
8. Representative Chemicals Related to Bepirovirsen Antisense Oligonucleotide Structure, Hepatitis B Antiviral Therapy, and Innate Immunity Research
Table 1. Chemicals Related to Bepirovirsen and Antisense Oligonucleotide Structure and Synthesis
Category | CAS No. | Aladdin Cat. No. | Name | Specification or Purity | Product Features and Applications |
Core antisense oligonucleotide—free acid form | 1403787-62-1 | Bepirovirsen | ≥93% | The active bepirovirsen oligonucleotide itself, used for studies of hepatitis B virus RNA targeting, RNase H-mediated transcript degradation, viral antigen reduction, and antisense oligonucleotide mechanisms of action. | |
Core antisense oligonucleotide—sodium salt form | 2563929-84-8 | Bepirovirsen sodium | ≥98% | Sodium salt form of bepirovirsen, used for studies of the drug substance, salt-form properties, viral RNA targeting, and antisense oligonucleotides related to chronic hepatitis B. | |
Solid-phase synthesis monomer—2′-O-(2-methoxyethyl) adenosine type | 251647-53-7 | 2′-O-MOE-rA(Bz) phosphoramidite | ≥98% | Protected adenosine phosphoramidite monomer for solid-phase synthesis of 2′-O-(2-methoxyethyl)-modified oligonucleotides, corresponding to an adenosine-modified unit in the wing regions of bepirovirsen. | |
Solid-phase synthesis monomer—2′-O-(2-methoxyethyl) guanosine type | 251647-55-9 | 2′-O-MOE-G(iBu) phosphoramidite | For DNA synthesis, molecular biology grade, ≥98% | Protected guanosine phosphoramidite monomer for solid-phase synthesis of 2′-O-(2-methoxyethyl)-modified oligonucleotides, corresponding to a guanosine-modified unit in the wing regions of bepirovirsen. | |
Solid-phase synthesis monomer—2′-O-(2-methoxyethyl)-5-methylcytidine type | 163759-94-2 | 2′-O-MOE-5-Me-C (Bz) | ≥98% (mixture of isomers) | Protected phosphoramidite monomer combining a 2′-O-(2-methoxyethyl) sugar modification and a 5-methylcytosine modification, used for synthesis of modified oligonucleotides related to the wing regions of bepirovirsen. | |
Solid-phase synthesis monomer—2′-O-(2-methoxyethyl)-5-methyluridine type | 163878-63-5 | 5-Me-2′-O-MOE-U phosphoramidite | For DNA synthesis, molecular biology grade, ≥98% (mixture of isomers) | Phosphoramidite monomer combining 2′-O-(2-methoxyethyl) and 5-methyluridine modifications, used for solid-phase synthesis of modified sequences related to the wing regions of bepirovirsen and other antisense oligonucleotides. | |
Direct wing-region structural unit—2′-O-(2-methoxyethyl)adenosine | 168427-74-5 | 2′-O-(2-Methoxyethyl)adenosine | —— | A modified nucleoside type present in the wing regions of bepirovirsen, used for studies of 2′-O-(2-methoxyethyl)adenosine structure, nucleic acid stability, analytical methods, and modified oligonucleotides. | |
Direct wing-region structural unit—2′-O-(2-methoxyethyl)guanosine | 473278-54-5 | 2′-O-(2-Methoxyethyl)guanosine | —— | A modified nucleoside type present in the wing regions of bepirovirsen, used for studies of 2′-O-(2-methoxyethyl)guanosine structure, nucleic acid stability, and modified nucleoside analysis. | |
Direct wing-region structural unit—2′-O-(2-methoxyethyl)-5-methylcytidine | 244105-55-3 | 5-Methyl-2′-O-(2-methoxyethyl)cytidine | For DNA synthesis, molecular biology grade, ≥98% | Contains both 2′-O-(2-methoxyethyl) and 5-methylcytosine modifications and corresponds to the cytidine type in the wing regions of bepirovirsen; used for studies of modified nucleoside structure, stability, and analysis. | |
Direct wing-region structural unit—2′-O-(2-methoxyethyl)-5-methyluridine | 163759-49-7 | 2′-O-MOE-5-Me-rU | ≥97% | The 5-methyluridine modification type actually present in the wing regions of bepirovirsen, used for studies of modified nucleoside structure, stability, degradation, and oligonucleotide analysis. | |
Modified nucleoside control—non-methylated uridine type | 223777-15-9 | 2′-O-(2-Methoxyethyl)uridine | ≥98% | Non-methylated 2′-O-(2-methoxyethyl)uridine, which can be used for structural and analytical-method comparisons with 5-methyluridine modifications; it is not a uridine unit present in the actual bepirovirsen sequence. | |
Central gap-region structural unit—5-methyldeoxycytidine | 838-07-3 | 2′-Deoxy-5-methylcytidine | ≥99% | A 5-methyldeoxycytidine modified nucleoside corresponding to the 5-methylcytidine type in the central deoxynucleotide region of bepirovirsen, used for studies of gap-region structure and nucleic acid analysis. | |
Modified base reference—5-methylcytosine | 554-01-8 | 5-Methylcytosine | ≥98% | A cytosine base methylated at the 5-position, used for studies of methylated nucleic acid bases, modified nucleoside composition, and related analytical methods. | |
Phosphorothioate backbone synthesis—sulfurizing reagent | 66304-01-6 | Beaucage reagent | Moligand™, ≥98% | A sulfurizing reagent used in phosphoramidite-based oligonucleotide synthesis to form phosphorothioate internucleotide linkages and to study conditions for constructing phosphorothioate antisense oligonucleotide backbones. |
Table 2. Hepatitis B Nucleos(t)ide Analogues, Prodrugs, and Parent Compounds
Category | CAS No. | Aladdin Cat. No. | Name | Specification or Purity | Product Features and Applications |
High-resistance-barrier nucleoside analogue—monohydrate | 209216-23-9 | Entecavir monohydrate | ≥99% | Entecavir monohydrate, used for studies of hepatitis B virus reverse transcriptase and DNA synthesis inhibition and as a mechanistic comparator between long-term viral replication suppression and bepirovirsen-mediated RNA targeting. | |
High-resistance-barrier nucleoside analogue—anhydrous form | 142217-69-4 | Entecavir | ≥98% | A guanosine nucleoside analogue that is phosphorylated intracellularly to its active triphosphate form, used for studies of hepatitis B virus reverse transcription, DNA synthesis, and antiviral pharmacology. | |
High-resistance-barrier nucleotide analogue prodrug—tenofovir disoproxil type | 202138-50-9 | Tenofovir disoproxil fumarate | ≥98% | The fumarate salt form of the oral tenofovir prodrug, used for studies of prodrug activation, inhibition of viral reverse transcription, and long-term control of viral replication in chronic hepatitis B. | |
High-resistance-barrier nucleotide analogue prodrug—tenofovir alafenamide type | 1392275-56-7 | Tenofovir alafenamide hemifumarate | ≥95% | The fumarate salt form of tenofovir alafenamide, used for studies of prodrug conversion, intracellular formation of active metabolites, and inhibition of hepatitis B virus replication. | |
Common parent compound of tenofovir prodrugs | 147127-20-6 | Tenofovir | Moligand™, ≥99% | Both tenofovir disoproxil and tenofovir alafenamide generate tenofovir following prodrug activation; tenofovir is subsequently phosphorylated intracellularly to the antivirally active tenofovir diphosphate. Used for studies of prodrug conversion, intracellular phosphorylation, and mechanisms of viral reverse-transcription inhibition. | |
Low-resistance-barrier nucleoside analogue—cytidine analogue | 134678-17-4 | Lamivudine | ≥99% | A representative cytidine nucleoside analogue used for studies of hepatitis B virus reverse-transcription inhibition, DNA synthesis, and mechanisms of resistance to low-resistance-barrier antiviral drugs. | |
Low-resistance-barrier nucleoside analogue—thymidine analogue | 3424-98-4 | Telbivudine | ≥98% | A thymidine nucleoside analogue used for studies of hepatitis B virus DNA polymerase inhibition, antiviral activity, and comparative resistance mechanisms. | |
Low-resistance-barrier nucleotide analogue prodrug—adefovir dipivoxil type | 142340-99-6 | Adefovir dipivoxil | Moligand™, ≥99% | A bis(pivaloyloxymethyl) ester prodrug of adefovir, used for studies of prodrug conversion, inhibition of hepatitis B virus reverse transcription, and previous nucleotide analogue treatment and resistance. | |
Parent compound of the adefovir dipivoxil prodrug | 106941-25-7 | Adefovir | ≥98% (HPLC) | Adefovir dipivoxil is hydrolyzed to form adefovir, which is subsequently phosphorylated intracellularly to the antivirally active adefovir diphosphate; used for studies of prodrug conversion, nucleotide analogue metabolism, and inhibition of hepatitis B virus DNA synthesis. |
Table 3. Research Tools for Toll-like Receptors and Innate Immune Mechanisms
Category | CAS No. | Aladdin Cat. No. | Name | Specification or Purity | Product Features and Applications |
Selective Toll-like receptor 8 agonist—hepatitis B immunology research | 2004677-13-6 | Selgantolimod | Moligand™ | A selective Toll-like receptor 8 agonist used for studies of innate immune activation, cytokine responses, and immune modulation in chronic hepatitis B; it can be used for comparative studies of immune-stimulatory mechanisms related to bepirovirsen. | |
Toll-like receptor 7/8 dual agonist—pathway activation control | 144875-48-9 | Resiquimod | Moligand™, ≥98% (HPLC) | A Toll-like receptor 7 and Toll-like receptor 8 agonist used for studies of nucleic acid sensing, innate immune signaling, inflammatory cytokine release, and receptor-activation controls. | |
Selective Toll-like receptor 8 inhibitor—pathway validation | 2165340-32-7 | CU CPT 9a, TLR8 inhibitor | ≥98% (HPLC) | A highly selective Toll-like receptor 8 inhibitor used to block receptor signaling and verify the dependence of nucleic acid- or small-molecule-induced innate immune responses on the Toll-like receptor 8 pathway. |
Note: The products listed above are representative Aladdin products related to the research described. Specific applications should be determined according to the product specification, batch COA, and the intended reaction or evaluation system. Additional information on product specifications, grades, and COAs can be found on the Aladdin website by searching by “product name/CAS/catalog number.”
References
[1] GSK. Hibsago (bepirovirsen) approved in Japan as first and only functional cure for chronic hepatitis B. 24 August 2026.
[2] Hou J, Lim SG, Buti M, et al. Phase 3 Results of Bepirovirsen Treatment for Chronic Hepatitis B Virus Infection. New England Journal of Medicine. 2026;394:2395–2406. DOI: 10.1056/NEJMoa2515131.
[3] Yuen MF, Heo J, Jang JW, et al. Safety, tolerability and antiviral activity of the antisense oligonucleotide bepirovirsen in patients with chronic hepatitis B: a phase 2 randomized controlled trial. Nature Medicine. 2021;27:1725–1734. DOI: 10.1038/s41591-021-01513-4.
[4] Yuen MF, Lim SG, Plesniak R, et al. Efficacy and Safety of Bepirovirsen in Chronic Hepatitis B Infection. New England Journal of Medicine. 2022;387:1957–1968. DOI: 10.1056/NEJMoa2210027.
[5] Grudda T, Hwang HS, Taddese M, et al. Integrated hepatitis B virus DNA maintains surface antigen production during antiviral treatment. Journal of Clinical Investigation. 2022;132(18):e161818. DOI: 10.1172/JCI161818.
[6] Taddese M, Grudda T, Belluccini G, et al. Transcription of hepatitis B surface antigen shifts from cccDNA to integrated HBV DNA during treatment. Journal of Clinical Investigation. 2025;135(6):e184243. DOI: 10.1172/JCI184243.
[7] Ermler ME, Delahaye JL, Jordan W, et al. Bepirovirsen induces innate immune activation in the liver potentially through TLR8 signaling. JHEP Reports. 2026;8(9):101923. DOI: 10.1016/j.jhepr.2026.101923.
[8] GSK. Bepirovirsen achieves breakthrough functional cure rates, with the potential to redefine the treatment of chronic hepatitis B. 28 May 2026.
[9] GSK. GSK and Sino Biopharmaceutical enter into an exclusive collaboration to accelerate the launch of bepirovirsen in China. 11 May 2026.
[10] GSK. Bepirovirsen accepted for regulatory review in China as a potential first-in-class functional cure for chronic hepatitis B. 30 March 2026.
[11] Sino Biopharmaceutical Limited. Voluntary Announcement: Data from Two Phase III Clinical Trials of Bepirovirsen Presented at EASL 2026. 28 May 2026.
For more related articles, see below:
Hepatitis B Virus (HBV) by PCR
Photo-activated nucleotide analog-mediated RNA-protein cross-linking experiments
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