Recently, the annual meeting of the European Association for the Study of the Liver (EASL) is being held.

At the conference, BoWang Pharmaceuticals presented the Phase I/IIa clinical research data of its innovative small interfering RNA (siRNA) therapy BW-20507 for the treatment of chronic hepatitis B (CHB) in a poster format.

BW-20507 is a siRNA molecule targeting the S region of hepatitis B virus (HBV) messenger RNA developed by Bowang Pharmaceutical based on its independent RNAi platform and unique proprietary technology. This poster summarizes the key research data of BW-20507 monotherapy in the treatment of chronic hepatitis B patients with virological suppression and nucleoside (NUC) naive treatment:

BW-20507, administered subcutaneously once every four weeks for three doses, significantly reduced HBsAg levels in a dose-dependent manner, with the maximum reduction observed in the 200 mg and 400 mg dose groups being 2.9~3.2 log10 IU/mL.

Among subjects with baseline HBsAg levels less than 1,000 IU/mL, 56% (5 of 9) achieved HBsAg clearance during the study.

Potent HBV DNA suppression was also observed in treatment-naive subjects not receiving concomitant NUC therapy.

BW-20507's outstanding antiviral efficacy and good safety and tolerability have laid the foundation for subsequent clinical development.

"These data represent important progress in the study of functional cure for chronic hepatitis B. What is particularly exciting is that after only three doses of BW-20507, some patients have already experienced HBsAg clearance, which is extremely rare in other siRNA monotherapy. These results bring new hope for functional cure for patients with chronic hepatitis B."

Based on the positive results, BoWang Pharmaceuticals plans to initiate Phase IIb clinical development of BW-20507 in 2025. The Phase IIb study of monotherapy is expected to start in the second quarter of 2025, and the Phase IIb study of combination therapy is expected to start in the third quarter, aiming to further evaluate the potential of BW-20507 in achieving functional cure of chronic hepatitis B.

Nearly 300 million people are affected

Chronic HBV infection is one of the main causes of liver disease worldwide. According to the World Health Organization (WHO), about 300 million people are chronically infected with hepatitis B virus (HBV) worldwide, resulting in more than 800,000 deaths each year. my country is a major country for hepatitis B. According to the "Guidelines for the Prevention and Treatment of Chronic Hepatitis B (2022 Edition)", there are about 86 million people with chronic hepatitis B virus infection in my country, and about 20 to 30 million chronic hepatitis B patients.

Achieving a cure for hepatitis B has been a difficult and hot topic in the field of hepatitis B research in recent years, and it is also the gospel that hundreds of millions of hepatitis B patients have been looking forward to. However, the cure for hepatitis B still faces some challenges. Through existing treatments, some patients can achieve clinical cure (functional cure).

Clinical cure means that after stopping treatment, the hepatitis B surface antigen (HBsAg) can remain negative, with or without the appearance of anti-HBs (hepatitis B core antibody), HBV DNA is below the minimum detection limit, liver biochemical indicators are normal, and covalently closed circular DNA (cccDNA) may still exist in the hepatocyte nucleus.

Currently, nucleoside drugs and long-acting interferon are commonly used antiviral drugs for the treatment of hepatitis B. Although they can control the disease to a certain extent, the proportion of patients who can be cured of hepatitis B after long-term treatment is still less than 10%.

Hope for cure

In recent years, the emergence of small nucleic acid drugs has brought hope for the clinical cure of hepatitis B.

Compared with traditional drugs, small nucleic acid drugs are highly targeted and can bind to hepatitis B virus mRNA or other key RNA sequences through the principle of base complementary pairing.

At the same time, small nucleic acid drugs can also affect the transcription process of cccDNA, putting cccDNA in a "silent" state, thereby achieving functional cure of hepatitis B, that is, HBSAg disappears in the patient's blood, hepatitis B virus DNA cannot be detected, liver function returns to normal, and liver inflammation is relieved, greatly reducing the risk of complications such as cirrhosis and liver cancer.

Currently, there are several hepatitis B clinical cure antisense oligonucleotides (ASO) and small interfering RNA (siRNA) candidate drugs undergoing clinical research around the world.
Among them, GlaxoSmithKline (GSK)'s GSK3228836 (Bepirovirsen) has made the fastest progress and is expected to be launched next year.

Its clinical trial data showed that Bepirovirsen exhibited significant efficacy in patients with chronic hepatitis B. In an early Phase 2b clinical trial, after 24 weeks of treatment, nearly one-third of patients achieved the disappearance of key hepatitis B virus markers, hepatitis B surface antigen (HBSAg) and hepatitis B virus DNA, in their bodies, which means that the virus's damage to the liver will be greatly reduced. Moreover, 24 weeks after stopping the drug, about 10% of patients were still able to maintain this clearance effect without significant side effects, which shows that the therapy does not "short-term suppress" the virus, but has the potential to achieve long-term stable therapeutic effects.

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

Xalnesiran, a siRNA drug developed jointly by Roche and Dicerna, can target conserved regions of the hepatitis B virus (HBV) genome to silence multiple HBV transcripts. It may be effective for patients with chronic HBV infection with or without immunomodulators. Phase II clinical studies are currently underway.

In addition, significant progress has been made in the research and development of domestic small nucleic acid drugs.

Brii Biopharma's hepatitis B siRNA drug candidate, BRII-835 (Elebsiran), has been included in the breakthrough therapy category by the CDE. The drug showed good tolerability and significant HBsAg-lowering effect in Phase 2 clinical trials.

Data from the Phase 1b clinical trial of HT-101, Xingyao Kunze's hepatitis B siRNA drug candidate, showed that all subjects in the HT-101 treatment group who participated in the extended follow-up maintained a good HBsAg reduction at 48 weeks.

Zhengda Tianqing's hepatitis B siRNA drug candidate, TQA-3038, is undergoing a Phase Ib/IIa clinical trial in patients with chronic hepatitis B.

In addition, companies such as Haobo Pharmaceutical and Bowang Pharmaceutical also have hepatitis B small nucleic acid drug candidates entering the clinical stage, bringing treatment hope to the majority of hepatitis B patients.

Conclusion

At present, new therapies such as siRNA have brought hope for the clinical cure of chronic hepatitis B patients, but clinical cure is not a complete cure. The medical community is still exploring and developing new methods, hoping to eventually find a solution to cure hepatitis B. For people who are not infected with the hepatitis B virus, vaccination with the hepatitis B vaccine is the best way to stay away from infection.

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