Gyre Therapeutics Completes Phase 3 Trial of F351 for CHB-Related Liver Fibrosis

On October 22, 2024, Gyre Therapeutics, Inc. (Nasdaq: GYRE), a biotechnology firm based in San Diego, announced a significant milestone in its Phase 3 clinical trial for the treatment of Chronic Hepatitis B (CHB)-associated liver fibrosis in the People’s Republic of China (PRC). The last patient participating in the trial, which examines the efficacy of the drug F351 (hydronidone), has completed the 52-week study period.

The results of this pivotal trial are anticipated to be reported by the first quarter of 2025. Han Ying, Ph.D., CEO of Gyre Therapeutics, highlighted the importance of this achievement for the company’s development pipeline. She expressed gratitude to all the patients, researchers, trial investigators, and supporting teams, emphasizing the potential of these results to advance the initiation of a Phase 2 clinical trial in the United States targeting Metabolic Dysfunction-Associated Steatohepatitis (MASH)-associated fibrosis in 2025.

The Phase 3 trial, identified as NCT05115942, was a randomized, double-blind, placebo-controlled, multicenter study that enrolled 248 patients across 39 clinical research hospitals in the PRC. Participants were randomly assigned in a 1:1 ratio to receive either F351 or a placebo, alongside basic antiviral therapy with entecavir for CHB. The primary goal was to observe a reduction in liver fibrosis by at least one stage after 52 weeks of treatment, measured using the Ishak Scoring System. The National Medical Products Administration (NMPA) of China had designated F351 as a “Breakthrough Therapy” in 2021.

F351, also known as hydronidone, is a structural analogue of Pirfenidone, an anti-fibrotic medication approved in the PRC for treating idiopathic pulmonary fibrosis. F351 has demonstrated effectiveness in inhibiting p38γ kinase activity and TGF-β1-induced excessive collagen synthesis in hepatic stellate cells (HSCs), which play a critical role in the development and progression of liver fibrosis. Additionally, F351 has shown anti-proliferative effects on HSCs. Its anti-fibrotic properties were confirmed in various established in vivo models of liver fibrosis, including mouse models of CCI4-induced liver fibrosis, DMN-induced liver fibrosis, and HSA-induced liver fibrosis, as well as a mouse model of MASH fibrosis.

Gyre Therapeutics, headquartered in San Diego, focuses on developing and commercializing treatments for MASH-associated fibrosis in the U.S. The company's strategy for F351 is based on its extensive research in MASH rodent models and clinical studies of CHB-induced liver fibrosis. Gyre is also advancing a diverse pipeline in the PRC through its indirect controlling interest in Gyre Pharmaceuticals. This includes the development of other therapeutic candidates like ETUARY, F573, F528, and F230.

Gyre Pharmaceuticals, a commercial-stage biopharmaceutical company, is committed to innovative drug development for organ fibrosis. Its flagship product, ETUARY (Pirfenidone capsule), was the first approved treatment for idiopathic pulmonary fibrosis (IPF) in the PRC in 2011 and has maintained a significant market share, with net sales of $112.1 million in 2023. Gyre Pharmaceuticals is also conducting a Phase 3 clinical trial for F351 in CHB-associated liver fibrosis, with topline data expected by the first quarter of 2025. The company is further developing treatments for chronic obstructive pulmonary disease (COPD), pulmonary arterial hypertension (PAH), and acute liver failure/acute-on-chronic liver failure (ALF/ACLF). In October 2023, Gyre Therapeutics acquired an indirect majority interest in Gyre Pharmaceuticals (also known as Beijing Continent Pharmaceuticals Co., Ltd.).