Once upon a time, "hepatitis B is incurable" was a heavy burden on countless patients. But more and more innovative therapies indicate that the era of clinical cure for hepatitis B is about to begin.

Recently, Cosun's innovative hepatitis B drug projects have achieved key breakthroughs one after another: GST-HG141 (nericovir) started Phase III clinical trials, marking a key step towards the drug's market launch and is expected to become a new milestone drug for hepatitis B worldwide; GST-HG131 was included in the list of breakthrough therapy products, becoming Cosun's second innovative drug in the field of hepatitis B treatment to be recognized as a breakthrough therapy.

As a result, Guangshengtang’s stock closing price increased by more than 100% for 10 consecutive trading days from July 3 to July 16.

Aiming to cure hepatitis B, Guangshengtang starts a comeback

Guangshengtang once dominated the Chinese liver disease market with its three first-line anti-hepatitis B virus generic drugs (entecavir, adefovir dipivoxil, and lamivudine).

However, with the advancement of national centralized procurement, the profits of generic drugs have shrunk significantly. For example, Cosuntech's entecavir won the bid in the expanded centralized procurement in 2019, with a bid price of only 0.27 yuan per pill. Cosuntech's financial report shows that the company has suffered losses in the past three years. The net profit attributable to shareholders of listed companies from 2022 to the first quarter of 2025 was -130 million yuan, -350 million yuan, -160 million yuan, and -30 million yuan, respectively.

Since it was listed on the Growth Enterprise Market in 2015, Cosuntech has clearly defined its transformation strategy to an innovative pharmaceutical company. In recent years, it has made every effort to increase its investment in research and development. Its financial report shows that its research and development expenses from 2022 to 2024 will reach 185 million yuan, 133 million yuan, and 44.0523 million yuan, respectively, which is one of the main reasons for its performance losses.

At present, Cosun's innovative drug projects have begun to see the light of day. In 2023, its innovative drug for the treatment of the new coronavirus, "Taizhongding", was approved for marketing and included in medical insurance. Although it encountered market changes and had limited benefits, it proved its strength in the research and development of antiviral drugs.

The more important pipeline of Cosunter lies in its liver disease treatment drugs. The company proposed the "Peak Plan", a roadmap for clinical cure of hepatitis B in 2015, and the three core projects have made good progress.
GST-HG141 (Nericovir): It is a new oral hepatitis B virus core protein regulator that affects the viral replication process by regulating the conformation of the hepatitis B virus core protein, thereby achieving antiviral activity. Its Phase II clinical data showed that the proportion of HBV DNA below the detection limit in the low-dose (50mg) and high-dose (100mg) groups of GST-HG141 was 84.0% and 81.5%, respectively, while the placebo was only 32.1%. At the same time, GST-HG141 is safe and well tolerated. At present, the drug has entered the critical stage of Phase III and is expected to become a milestone innovative drug for the global hepatitis B antiviral treatment.

GST-HG131: It is the only oral hepatitis B surface antigen (HBsAg) inhibitor in the world that has completed Phase II clinical trials. Its innovative treatment mechanism directly hits the core difficulty of curing hepatitis B - it can induce HBV-RNA degradation, thereby reducing HBsAg levels. In the Phase II clinical trial, after three months of administration, the average HBsAg level of patients dropped to 12.88% of the original value, a decrease of 87.12%; the maximum decrease reached 97.71%, and 60% of patients showed significant immune responses.

GST-HG141 and GST-HG131 have been recognized as “breakthrough therapeutics” and their review process has been accelerated.

Guangshengtang's larger strategic layout lies in the synergy of dual drugs. In March 2025, its innovative "triple all-oral regimen" (GST-HG141+GST-HG131+nucleoside drugs) was included in the "Pilot Project for Optimizing the Review and Approval of Clinical Trials of Innovative Drugs" and obtained approval for clinical trial applications. Based on nucleoside analog drugs (NAs), this sequential therapy combines GST-HG141, which can reduce the cccDNA virus pool, with GST-HG131, which can inhibit HBsAg, in order to achieve the goal of clinical cure of hepatitis B.

In addition, Guangshengtang also has a hepatitis B surface antigen inhibitor GST-HG121, but it is currently in the Phase I clinical trial stage.

This year, Cosunter will raise RMB 977 million through a private placement, of which RMB 598 million will be directly used for innovative hepatitis B drug research and development projects, including the Phase III clinical research and market registration project of GST-HG141 and the Phase II and Phase III clinical research and market registration project of GST-HG131 combined with GST-HG141, to further promote the rapid clinical development of the pipeline.

Hepatitis B treatment enters a new stage

Hepatitis B is caused by the hepatitis B virus (HBV). It is widely prevalent in countries around the world and is one of the main causes of liver disease worldwide. According to statistics from the World Health Organization, in 2022, there were 254 million people with chronic hepatitis B infection and about 1.2 million new infections worldwide. Hepatitis B patients in China account for about one-third of the global total, and it has become one of China's major public health issues.

The dilemma of hepatitis B treatment has lasted for decades. Existing treatments such as nucleoside drugs can only inhibit viral replication, but cannot eliminate the viral reservoir, and require lifelong medication; interferon therapy has significant side effects and a cure rate of less than 10%.

In recent years, various innovative treatments for hepatitis B have emerged, making clinical cure (functional cure) of hepatitis B gradually possible. Clinical cure means that after stopping treatment, the hepatitis B surface antigen (HBsAg) remains negative and HBV DNA is below the minimum detection limit.

Titer data show that there are nearly 200 new hepatitis B drugs under development worldwide. From the perspective of mechanism, they are mainly divided into HBsAg inhibitors, capsid inhibitors, RNA interference (siRNA), antisense oligonucleotides (ASO) and other types.
Capsid inhibitors have been an important research direction in the field of hepatitis B treatment in recent years. Currently, no new drugs with this mechanism have been approved for marketing worldwide, but nearly 50 capsid inhibitors for hepatitis B treatment are under development. Among them, the ones with faster progress include GST-HG141 of Cosun Pharmaceutical, which has started Phase III clinical trials, and mofecillin mesylate (GLS4) of East Sunshine Pharmaceutical and ZM-H1505R of Zhimeng Pharmaceutical, which have also entered Phase III clinical trials.

HBsAg inhibitors are a class of drugs that specifically target hepatitis B surface antigen (HBsAg), and there are currently no drugs with this mechanism on the market. Drugs under development include GST-HG131 (clinical phase II) from Cosun, HBsAg neutralizing antibody BM012 (clinical phase II) from Biominsai/Xingyao Kunze Bio, and HBsAg autologous TCR-T cell therapy SCG101 (clinical application) from Xinghande Bio.

Small nucleic acid therapies such as ASO (antisense oligonucleotide) and RNA interference (siRNA) are another major category of clinical cures for hepatitis B that are highly anticipated. Compared with other 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 a functional cure for hepatitis B.

GlaxoSmithKline's GSK3228836 (Bepirovirsen) is the world's fastest-progressing ASO therapy for hepatitis B, and has entered Phase III clinical trials in 2022. The latest clinical data show that chronic hepatitis B patients who received 12 or 24 weeks of Bepirovirsen treatment were followed up for up to 2.5 years. Among the 11 complete response patients who did not receive NAs treatment, 73% (8/11) achieved functional cure, of which 6 maintained functional cure for up to 24 months; among the 11 complete response patients who received NAs treatment, 82% (9/11) achieved functional cure and discontinued NAs, of which 7 maintained functional cure for up to 24 months. The drug is expected to be available in 2026 at the earliest.

in China planning to develop small nucleic acid therapies for hepatitis B.

Elebsiran (formerly known as BRII-835/VIR-2218) of Brii Biopharma has shown good tolerability and significant HBsAg reduction effects in Phase II clinical trials and has been included in the Breakthrough Therapy category by the CDE. In addition, HT-101 of Xingyao Kunze, HRS-5635 of Hengrui Medicine, TQA-3038 of Zhengda Tianqing, AHB-137 of Haobo Pharmaceuticals, and BW-20507 of Bowang Pharmaceuticals have entered the Phase II clinical trial stage, bringing hope for treatment to the majority of hepatitis B patients.
Conclusion

Cosuntang's transformation from generic drugs to innovative drugs reflects the epitome of China's pharmaceutical industry upgrade. The company chose liver disease, a field with a large patient base and far-from-met clinical needs, and concentrated resources to overcome difficulties, and the value of innovation is about to be realized.

For hepatitis B patients, in addition to Guangshengtang’s “Peak Plan”, there are many innovative therapies that show the dawn of “cure”, and the darkness shrouded by the virus will eventually be illuminated.

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