Recently, GlaxoSmithKline PLC (GSK) announced that its antisense oligonucleotide (ASO) drug Bepirovirsen (brand name Hibsago) received FDA approval for market launch, indicated for combination with nucleos(t)ide analogues in the treatment of adults with chronic hepatitis B who have no cirrhosis and HBsAg ≤3000 IU/mL.

As the world's largest hepatitis B country, China not only bears nearly one-third of the global patient population but is also becoming the most active market for hepatitis B functional cure research and development. As of the third quarter of 2026, more than 20 domestic pharmaceutical companies have established hepatitis B functional cure pipelines, covering multiple technology routes including small nucleic acids, small molecule capsid inhibitors, and immunotherapy, with clinical stages ranging from early exploration to completed Phase III enrollment. In this race ignited by GSK, which domestic companies are leading?

ASO Drug Achieves Efficacy Breakthrough, Multiple Technology Routes Compete in Domestic Pipelines

The Phase III clinical data for Bepirovirsen showed that in the Chinese population subgroup, after completing a 24-week limited course of Bepirovirsen, the overall functional cure rate at week 72 of follow-up reached 24%, with the cure rate in the advantaged population (baseline HBsAg 100-200 IU/mL) reaching as high as 61%. In comparison, the existing standard nucleos(t)ide analogue monotherapy for one year yields a functional cure rate of less than 1%, and pegylated interferon treatment also achieves only about a 30% cure rate in the advantaged population.

GSK predicts that Bepirovirsen's peak global annual sales will exceed 2 billion pounds, approximately 19.5 billion yuan. Citigroup, Goldman Sachs, and other institutions forecast a range of 1.6-2.5 billion pounds. After first being approved in the Japanese market, the single-injection price exceeded 7,000 yuan, with the full 24-week course costing approximately 400,000 yuan. Regarding the domestic market, according to Frost & Sullivan, China's hepatitis B drug market is expected to grow from 14.61 billion yuan in 2025 to 77.04 billion yuan in 2034, with a compound growth rate of 20.1%. Goldman Sachs estimates that if Bepirovirsen successfully launches in China, peak annual sales could reach 5 billion yuan.

Currently, domestic hepatitis B functional cure research and development has formed four parallel technology routes, corresponding to different mechanisms of action. The first is the small nucleic acid route, which directly targets hepatitis B virus RNA to inhibit surface antigen expression, represented by GSK's Bepirovirsen. Among domestic companies, Haobo Medicine's AHB-137 and Hengrui Pharmaceuticals' HRS-5635 belong to this route. The second is the small molecule capsid inhibitor route, which interferes with hepatitis B virus nucleocapsid assembly to inhibit viral replication and reduce surface antigen, with representative companies including Guangzhaotang's Nerycovir and Dongyangguang Pharmaceutical's Morphothiadin Mesylate. The advantage of such drugs is oral administration and good compliance, but monotherapy cure rates are limited, usually requiring combination therapy. The third is the immunotherapy route, which clears the virus by rebuilding the patient's own immune system, including pegylated interferon, PD-L1 antibodies, and therapeutic vaccines. Representative companies include Tebao Biology's Pegbine, Geely Pharmaceutical's ASC22, and Tengsheng Biopharma's BRII-179.

Haobo and Tebao Lead, Hengrui and Guangzhaotang Follow Closely Behind

Divided by clinical progress and maturity, Haobo Medicine, Tebao Biology, and Zhengda Tianqing are in the industry's first tier. Among them, Haobo Medicine's AHB-137 is currently the product whose clinical data most closely approaches or even partially surpasses GSK's Bepirovirsen. Phase II data disclosed in July 2026 showed that in treatment-naive patients with baseline HBsAg 100-1000 IU/mL, the clinical cure rate with 16-week monotherapy exceeded 70%.

Tebao Biology is the only domestic company with an already marketed hepatitis B cure product. Its Pegbine (pegylated interferon α-2b) was approved in October 2025 for a new "clinical cure" indication, becoming China's first hepatitis B drug approved with clinical cure as an endpoint. Registered clinical data showed that in the advantaged population of nucleotide-experienced patients with low surface antigen (HBsAg<1500 IU/mL), the clinical cure rate was approximately 30%; related extended follow-up results disclosed in an AASLD (American Association for the Study of Liver Diseases) annual meeting abstract showed that the 104-week clinical cure durability was approximately 90%.

Zhengda Tianqing reached a strategic cooperation with GSK in May 2026, obtaining exclusive commercialization rights for Bepirovirsen in mainland China. With its channel advantages and medical insurance negotiation experience in the liver disease field cultivated over many years, Zhengda Tianqing should have been the best vehicle for Bepirovirsen's commercialization in China. Unexpectedly, however, Bepirovirsen's first marketing application in May 2026 was not approved by the NMPA, most likely due to considerations regarding the matching of the indicated population with the baseline characteristics of Chinese patients, which has left a catch-up window for domestic companies still in research and development. In comparison, Zhengda Tianqing's advantage is fully maximized commercialization capability, while its disadvantage is reliance on external pipelines and lack of self-developed cure technology reserves.

In addition, the pipelines under development at Guangzhaotang, Dongyangguang Pharmaceutical, and Hengrui Pharmaceuticals are also quite noteworthy. Guangzhaotang is the company with the most comprehensive hepatitis B cure pipeline layout in China, possessing two core products: the nucleocapsid inhibitor Nerycovir (GST-HG141) and the surface antigen inhibitor GST-HG131, both included as national breakthrough therapeutic varieties. Among them, Nerycovir's Phase III clinical trial completed enrollment of all 578 subjects in February 2026, led by Academician Li Lanjuan and Professor Wang Guiqiang, and is a project supported by the National Major Science and Technology Special Project. Guangzhaotang's core highlight is the "131+141" all-oral combination cure regimen, which requires no injections and offers patient compliance far superior to ASO and interferon. However, the monotherapy cure data has not yet been disclosed, and although the combination regimen's Phase II data has highlights, the Phase III unblinding results still carry uncertainty.

Dongyangguang Pharmaceutical's Morphothiadin Mesylate is one of the earliest hepatitis B capsid inhibitors to enter clinical trials in China, but after many years, the drug is still in Phase III clinical trials, progressing far slower than market expectations. The core problem with Morphothiadin is that it must be combined with ritonavir for boosting, and ritonavir itself has significant side effects and brings drug interaction risks. In addition, safety issues observed in early clinical trials, such as early treatment ALT elevation and hypertriglyceridemia, have also limited its applicable population. Combined with the company's strategic focus shifting to influenza and metabolic areas in recent years, with insufficient R&D resource investment in the hepatitis B pipeline, Morphothiadin's market prospects have degenerated from "frontrunner" to "follower."

Hengrui Pharmaceuticals' HRS-5635 is an siRNA drug. As a leading domestic pharmaceutical company, Hengrui's advantages lie in ample funding, strong clinical execution capability, and a well-established commercialization network, but Hengrui's problem is its late entry. HRS-5635 registered and initiated Phase III clinical trials in May 2026. Although it holds a leading position in the siRNA track, in terms of the entire hepatitis B cure race, its first-mover advantage may already be lost, and compared with the ASO route, siRNA has no obvious advantage in the depth of surface antigen clearance, requiring more excellent clinical data to achieve differentiated breakthrough.

Meanwhile, Geely Pharmaceutical and Tengsheng Biopharma are at a disadvantage in the hepatitis B cure race. Geely Pharmaceutical's ASC22 (Envafolimab) is the world's first subcutaneous PD-L1 antibody hepatitis B therapy to enter clinical trials, with Phase IIa data showing a 42.9% cure rate in the population with baseline HBsAg≤100 IU/mL. However, that data was based on a sample size of only 7 patients, with limited statistical persuasiveness. In the years since, ASC22 has remained in the Phase IIb expansion cohort stage, with no progress toward Phase III, and its R&D progress has nearly stalled. Tengsheng Biopharma's BRII-179 is a therapeutic vaccine. Phase II ENSURE study data showed some effect on immunological control of hepatitis B virus, but there is still a large gap from the goal of functional cure. Moreover, affected by the decline of the company's COVID-19 antibody business, cash flow has remained tight, R&D investment has shrunk significantly, and the advancement speed of the hepatitis B pipeline has noticeably slowed.