Breakthrough Clinical Results
Gyre Therapeutics announced positive Phase 3 results for Hydronidone (F351) in treating liver fibrosis associated with chronic hepatitis B (CHB) in China. The trial met its primary endpoint, demonstrating statistically significant fibrosis regression at Week 52 compared to placebo (52.85% vs. 29.84%, P=0.0002). Hydronidone showed a favorable safety profile. Gyre plans to submit a New Drug Application (NDA) to the NMPA in Q3 2025 and initiate a Phase 2 trial in the U.S. for MASH-associated liver fibrosis in 2H2025. This could make Hydronidone the first therapy specifically indicated for reversing liver fibrosis in CHB patients.
Key Highlights
- Hydronidone met the primary endpoint in a pivotal Phase 3 trial, showing statistically significant fibrosis regression in CHB patients.
- The drug demonstrated a favorable safety and tolerability profile with a low incidence of serious adverse events.
- Gyre plans to file an NDA with the NMPA in Q3 2025 and initiate a Phase 2 trial in the U.S. for MASH-associated liver fibrosis.
- Hydronidone has the potential to be the first therapy to reverse liver fibrosis in CHB patients.
Study Design Parameters
Study Design Parameters and Endpoints in Key Liver Fibrosis Trials
Study Design Parameters
Multiple Non-Invasive Assessment Methods
- Enhanced Liver Fibrosis (ELF) Test: Meta-analysis of 9 studies evaluating diagnostic performance
- Magnetic Resonance Imaging (MRI) Methods: Studies using 3T MRI with renal cortex reference and magnetic resonance elastography (MRE) compared to transient elastography
- CT-based Assessment: Evaluation of deep convolutional neural network (DCNN) based on CT images
- Liver Surface Nodularity (LSN) Score: Meta-analysis of 6 studies
- Ultrasound-based Methods: Studies of real-time tissue elastography (RTE) and deep learning Radiomics of elastography (DLRE) using 2D-SWE images
Key Clinical Trials
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Vitamin D Supplementation Trial:
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Double-blinded placebo-controlled clinical trial
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46 MASLD patients block-matched for sex and BMI
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Randomized to 4000 IU/d vitamin D or placebo for 12 weeks
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HOMA-IR Study:
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Retrospective, cross-sectional multicenter study
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361 patients with biopsy-proven NAFLD without type 2 diabetes
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Simple random sampling with 7:3 ratio for estimation and validation groups
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FIB-4 Index Study:
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522 HCV patients who achieved SVR by interferon-based therapy
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Annual recalculation of FIB-4 index based on laboratory values after SVR
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ELF Test Evaluation:
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300 patients with ELF scores assayed at time of liver biopsy
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Median follow-up of 6.1 years
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Deep Learning System Development:
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Development dataset: 7,461 patients with pathologically confirmed liver fibrosis
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Test dataset: 891 patients
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Comparison subset: 421 patients
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Subcutaneous Adipose Tissue Study:
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62 NAFLD patients (60% men)
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12-month treatment with synbiotic or placebo
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Vibration-controlled transient elastography (VCTE) for fibrosis assessment
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CD34+ Cell Transplantation Study:
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Human peripheral blood CD34+ cells from healthy volunteers
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Nude rats injected with carbon tetrachloride for 3 weeks
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Different doses tested: saline (control), 1×10⁵, 5×10⁵, or 2×10⁶ CD34+ cells/kg body weight
Endpoints
Primary Outcomes
- Changes in non-invasive tests (NITs) for fibrosis at 6-12 months
- Histological fibrosis score of the liver
- Liver fibrosis area
- Improvement in liver fibrosis by at least 1 fibrosis stage
- Liver stiffness measurement on transient elastography
Secondary Outcomes
- Weight loss
- Changes in insulin resistance
- Changes in lipid profile
- Liver-related mortality
- New-onset cirrhosis
- Serological levels of fibrosis markers
- Adverse events
- Withdrawals
Non-Invasive Tests Used
- ALT (alanine aminotransferase)
- AST (aspartate aminotransferase)
- FIB-4 (fibrosis-4 score)
- Non-alcoholic fatty liver disease fibrosis score (NFS)
- Gamma-glutamyl transferase (GGT)
- Transient elastography (TE)
Diagnostic Performance Metrics
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For Enhanced Liver Fibrosis (ELF) Test:
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Pooled sensitivity for significant fibrosis: 83% (95% CI=0.80-0.86)
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Pooled specificity for significant fibrosis: 73% (95% CI=0.69-0.77)
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Pooled sensitivity for cirrhosis: 80% (95% CI=0.75-0.85)
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Pooled specificity for cirrhosis: 71% (95% CI=0.68-0.74)
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For Liver Surface Nodularity (LSN) Score:
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Pooled sensitivity/specificity/AUC for significant fibrosis: 68%/89%/0.90
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Highest sensitivity in diagnosing advanced fibrosis (88%)
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Highest specificity in diagnosing significant fibrosis (89%)
Recent Studies
Recent Studies on Liver Fibrosis
Study 1: EGCG Treatment for NAFLD/NASH-related Liver Fibrosis
- Intervention: (-)-epigallocatechin-3-gallate (EGCG), a major component of Green tea catechins (GTCs)
- Study design: Male Sprague-Dawley rats given diethylnitrosamine and high-fat diet, with 0.01% or 0.1% EGCG in drinking water
- Efficacy: EGCG inhibited development of GST-P-positive foci by decreasing hepatic triglyceride content, reducing hepatic fibrosis, lowering oxidative stress, attenuating inflammation, and inhibiting excessive hepatocyte proliferation
- Safety: No specific safety concerns reported
Study 2: HMGB1 siRNA for Liver Fibrosis
- Intervention: HMGB1 siRNA transfected into HSC-T6 cells
- Study design: Hepatic fibrosis induced in rats through serial subcutaneous injections of dimethylnitrosamine
- Efficacy: HMGB1 siRNA treatment inhibited synthesis of α-SMA and collagen types I and III in transfected HSCs
- Findings: HMGB1 was upregulated during liver fibrosis and its expression was closely correlated with collagen deposition
Study 3: Bushen Jianpi Formula (BSJPF) for Chronic Hepatitis B
- Intervention: BSJPF (also known as Lingmao formula) combined with entecavir (ETV)
- Study design: 640 patients randomized 1:1 to BSJPF+ETV or placebo+ETV for 96 weeks
- Efficacy: Higher rate of HBsAg loss (5.5% vs 1.8%), better HBsAg reduction ≥1 lg·IU/mL (11.1% vs 5.9%), and better liver fibrosis improvement (35.5% vs 11.8%)
- Safety: Similar adverse events between groups except for abnormal kidney function (0.0% in treatment group vs 2.2% in control group)
Study 4: CCL11 Targeting for NAFLD
- Intervention: CCL11 neutralization or antagonism (C-C motif ligand 11 chemokine)
- Study design: NAFLD induced in mice with high-fat high-carbohydrate diet; CCL11 targeting via genetic deletion or pharmaceutical inhibition
- Efficacy: CCL11 knockout mice showed ameliorated NAFLD with decelerated body weight gain, improved insulin sensitivity, dampened lipid accumulation, reduced immune cell infiltration, and weakened liver fibrosis
- Additional finding: Positive correlation between CCL11 expression and NAFLD parameters identified in human patients
Drug used in other indications
Hydronidone Clinical Trials
Based on the available information, Hydronidone is currently being trialed primarily for Chronic Hepatitis B (CHB)-associated liver fibrosis. The context does not mention any other indications for which Hydronidone is being tested.
The primary clinical trial described is a 52-week multicenter, randomized, double-blind, placebo-controlled, phase II study conducted at 8 centers in China focused on liver fibrosis treatment.
The intervention model for this liver fibrosis trial includes: * Daily oral administration of Hydronidone at three different dosage levels (180 mg/day, 270 mg/day, or 360 mg/day) or placebo * All enrolled subjects also received entecavir 0.5 mg/day * The trial utilized a second liver biopsy at week 52 to assess outcomes * Primary endpoint was fibrosis improvement defined as reduction of at least 1 Ishak score at week 52 of treatment
Additionally, a pharmacokinetic study was conducted as an open-label, three-period, multiple-dosage, self-controlled clinical trial investigating interaction between Hydronidone and entecavir in healthy Chinese male subjects: * Subjects took Hydronidone 60 mg, q8h, for 7 days in period 1 * In period 2, they were given entecavir 0.5 mg once daily for 9 days * Then, Hydronidone and entecavir were given in combination for 6 days (days 20-26)
No information is available about Hydronidone trials for indications other than liver fibrosis.