Hydronidone met the primary endpoint in a pivotal phase 3 trial evaluating its efficacy and safety for the treatment of liver fibrosis in patients with chronic hepatitis B (CHB) in China, according to a press release from Gyre Therapeutics.1
The trial met its primary endpoint for ≥1-stage regression in liver fibrosis compared to placebo. Based on these data, Gyre plans to file a New Drug Application with China’s NMPA in the third quarter of 2025 and is preparing to file an investigational new drug (IND) application in the third quarter of 2025. Pending IND clearance, the company plans to initiate a phase 2 trial in the US evaluating Hydronidone for the treatment of metabolic dysfunction-associated steatohepatitis (MASH)-associated fibrosis in the second half of 2025.1
“The fibrosis regression in our trial marks a breakthrough in the treatment of CHB fibrosis," said Lungen Lu, MD, dean of the department of gastroenterology at Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, and lead principal investigator.1 "With no approved anti-fibrotic therapies for this liver disease currently available, Hydronidone has the potential to transform the treatment landscape and offer new hope to patients facing the serious risks of cirrhosis, liver failure, and hepatocellular carcinoma."
Hydronidone (F351) is a structural analogue of Pirfenidone, for which Gyre received first-in-class approval in China in 2011 for the treatment of idiopathic pulmonary fibrosis (IPF). Hydronidone exhibits enhanced potency in inhibiting p38γ kinase activity and TGF-β1-induced collagen synthesis in hepatic stellate cells (HSCs), key drivers of liver fibrosis. It also demonstrates anti-proliferative activity in HSCs through upregulation of Smad7, which downregulates TGF-βRI, thereby suppressing both the p38γ and Smad2/3 fibrogenic pathways.1,2
The 52-week, multicenter, double-blind, placebo-controlled trial enrolled 248 patients with CHB fibrosis across 39 hospitals in China. Participants were randomly assigned in a 1:1 ratio to receive either oral Hydronidone 270 mg/day or placebo, in addition to background entecavir antiviral therapy.1
The primary endpoint was the efficacy of fibrosis regression, defined as a decrease in the Ishak stage score of liver fibrosis ≥ 1 after 52 weeks of treatment compared to baseline. A key secondary endpoint was a ≥1-grade reduction in liver inflammation, as assessed by the Scheuer scoring system, after 52 weeks of treatment compared to baseline, without progression of fibrosis.1
What You Need to Know
Hydronidone significantly met the primary endpoint of ≥1-stage liver fibrosis regression in patients with chronic hepatitis B in a 52-week phase 3 trial, marking a potential breakthrough in CHB fibrosis treatment where no anti-fibrotic therapies currently exist.
The trial demonstrated a favorable safety profile with no treatment-related severe adverse events and a statistically significant improvement over placebo. The results were consistent with prior phase 2 findings, strengthening confidence in Hydronidone's clinical potential.
Based on these results, Gyre Therapeutics plans to file a New Drug Application with China’s NMPA in Q3 2025 and submit an IND for a US-based phase 2 trial targeting MASH-associated fibrosis in the second half of 2025, indicating a strategic push for global development.
Results showed the trial met its primary endpoint, with a statistically significant proportion of patients receiving Hydronidone achieving a ≥1-stage regression in liver fibrosis compared to placebo (P = .0002). Of note, these results are consistent with the efficacy and safety outcomes observed in Gyre’s prior phase 2 trial.1
Safety analyses showed Hydronidone was well tolerated, with a comparable incidence of serious adverse events (4.88% vs 6.45% in the placebo group) and no discontinuations due to adverse events in either group. Most adverse events were mild or moderate and unrelated to Hydronidone, while a small number of severe adverse events occurred, none of which were considered related to the trial drug.1
“These landmark phase 3 results represent a major step forward for Gyre and for the millions of Chinese patients living with CHB fibrosis,” Han Ying, PhD, CEO of Gyre Therapeutics, said in a press release.1 “Pending regulatory approval in China, Hydronidone may become the first therapy specifically indicated for reversing liver fibrosis in CHB patients and the foundation for broader expansion into metabolic dysfunction-associated steatohepatitis (“MASH”)-related fibrosis in the United States.”
References
1.Gyre Therapeutics. Gyre Therapeutics’ Hydronidone Met the Primary Endpoint and Demonstrated Statistically Significant Fibrosis Regression in Pivotal Phase 3 Trial for the Treatment of CHB-associated Liver Fibrosis in China. May 22, 2025. Accessed May 22, 2025. https://ir.gyretx.com/news-releases/news-release-details/gyre-therapeutics-hydronidone-met-primary-endpoint-and
