Breakthrough Hepatitis B 'Functional Cure' Drug Bepirovirsen (GSK3228836) Set for 2026 Approval

Chronic hepatitis B (HBV) infection is one of the leading causes of liver disease worldwide.。According to the "Guidelines for the Prevention and Treatment of Chronic Hepatitis B (2022 Edition)",China has approximately 86 million people with chronic hepatitis B virus infection and about 20 to 30 million patients with chronic hepatitis B.

Achieving a cure for hepatitis B has always been a difficult and hot topic in the field of hepatitis B research in recent years.. At present, clinically used for hepatitis B treatment in ChinaNucleos(t)ide analogues and interferons can only suppress viral replication, but cannot completely eliminate the virus.Covalently closed circular DNA (cccDNA) is the template for hepatitis B virus replication. It exists in the form of a minichromosome in the nucleus of hepatocytes and is extremely stable.Existing TherapiesOnce the medication is stopped, cccDNA will restart viral replication, leading toRelapse，Therefore, patients often need to take medication for a long term or even for life.。

However,The emergence of small nucleic acid drugs has brought new hope for the functional cure of hepatitis B.Small nucleic acid drugs mainly include antisense oligonucleotides (ASO), small interfering RNA (siRNA), etc., which have high targeting compared to traditional drugs. They can bind to the mRNA of the hepatitis B virus or other key RNA sequences through the principle of base complementary pairing. Taking ASO drugs as an example, after binding to the target RNA, they recruit nucleases to degrade the target RNA, therebyBlock the synthesis of hepatitis B virus proteins, inhibit viral replication and transmission.。

At the same time,Small nucleic acid drugs can also affect the transcription process of cccDNA., putting cccDNA into a "silent" state, thereby achieving functional cure of hepatitis B, meaning the disappearance of HBSAg in the patient's blood, undetectable hepatitis B virus DNA, restored liver function, alleviated liver inflammation, and significantly reduced risk of complications such as liver cirrhosis and liver cancer.

|GSK Leads, Expected to Launch as Early as 2026

Currently, multiple hepatitis B clinical cure antisense oligonucleotide (ASO) and small interfering RNA (siRNA) candidate drugs are undergoing clinical research globally.

GSK's GSK3228836 (Bepirovirsen) is the most advanced and is expected to be launched next year.。According to the 2024 financial report published on the official website of GlaxoSmithKline (GSK), GSK3228836 (bepirovirsen), the world's first functional cure for hepatitis BLaunch Time Confirmed for 2026，Priority will be given to submitting New Drug Application (NDA) in the United States, China, Europe, and Japan, with official approval decisions from the U.S. and Japan expected by 2026.

Published clinical trial data shows that 30% of patients can stop medication without recurrence. In the early phase 2b clinical trial, after 24 weeks of treatment, nearly one-third of patients achieved the disappearance of key markers of hepatitis B virus in the body: hepatitis B surface antigen (HBsAg) and hepatitis B virus DNA. This indicates a significant reduction in viral damage to the liver. Moreover, 24 weeks after discontinuing the medication, about 10% of patients maintained this clearance effect without significant side effects. This suggests that the therapy does not merely "temporarily suppress" the virus but has the potential to achieve long-term stable therapeutic effects.

In addition to bepirovirsen,GSK also has several small nucleic acid therapies for hepatitis B in development, such as GSK5637608 (original R&D code: JNJ-3989 (ARO-HBV)), which is currently undergoing Phase II clinical trials.

Xalnesiran, an siRNA drug developed through a collaboration between Roche and Dicerna, which can target the conserved regions of the hepatitis B virus (HBV) genome to silence multiple HBV transcripts, may be effective for patients with chronic HBV infection, either in combination with or without immunomodulators. Since 2021, RG6346 has been undergoing Phase II combination therapy trials in multiple countries.

Vir BiotechnologyA Phase 2 clinical trial evaluating the investigational therapyTobevibart and Elebsiran Combination(With or without pegylated interferon alpha)Efficacy and safety in patients with chronic hepatitis B (CHB). Studies show that in participants with lower baseline hepatitis B surface antigen (HBsAg) levels (<1000 IU/mL),Both combination therapy regimens demonstrated high HBsAg clearance rates, with efficacy and safety results supporting further development to evaluate the potential for achieving functional cure.

|Significant progress has been made in the development of small nucleic acid drugs produced in China.

Brii Biosciences' HBV siRNA Candidate Drug——BRII-835 (Elebsiran) has been designated as a breakthrough therapy by the CDE, demonstrating good tolerability and significant HBsAg reduction in Phase 2 clinical trials.

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▲ Overview of Small Nucleic Acid Companies in China (CXO Companies Not Included in This Table)

Ascletis PharmaASC22 (Envafolimab) is a subcutaneously injected PD-L1 single-domain antibody that can relieve T-cell exhaustion and promote immune clearance of HBV-infected cells. The Phase IIb extension study (AASLD 2023) showed that after 24 weeks of combination therapy with NAs, 21.1% of patients achieved HBsAg loss, demonstrating significant immunomodulatory advantages and good tolerability.

Xingyao Kunze's HBV siRNA Candidate Drug —— HT-101Phase 1b clinical trial data showed that all subjects in the HT-101 dosing group who participated in the extended follow-up maintained a good reduction in HBsAg at 48 weeks.

China Biologic's HBV siRNA Candidate Drug – TQA-3038A Phase Ib/IIa clinical trial is ongoing in patients with chronic hepatitis B.

Novel therapies like siRNA have brought hope for clinical cure to patients with chronic hepatitis B, but clinical cure does not mean complete cure. The medical community is still exploring and developing new methods in the hope of eventually finding a definitive solution for hepatitis B. For those who have not been infected with the hepatitis B virus, getting vaccinated against hepatitis B remains the best way to prevent infection.

Sina Medicine Comprehensive

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