The 75th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) was convened from November 15-19, 2024 in San Diego, USA. Hansoh Pharma presented four research findings on tenofovir amibufenamide (TMF, brand name: Hengmu) in poster format.
The AASLD Annual Meeting is one of the most significant and renowned conferences in the field of hepatology throughout the world. Each year, it attracts nearly 10,000 hepatologists and professionals engaged in liver disease research from all corners of the globe. Participants gather to exchange and share the latest groundbreaking research findings, treatment guidelines, and therapeutic approaches in the field of hepatology.
Four major research findings were presented on tenofovir amibufenamide, the first domestically developed oral antiviral drug for hepatitis B in China, at the conference, including randomized clinical trials (RCTs), mechanism studies, and real-world studies.
Among them, the first prospective, multi-center RCT study targeting individuals with normal ALT levels suffering from HBV confirmed that TMF provides significant benefits for this population. A prospective clinical study revealed the potential immune mechanism of TMF's antiviral effect during the early stages of treatment. A retrospective real-world study indicated that the efficacy and safety of TMF and TAF were comparable after 48 weeks of treatment. Another prospective real-world study found that TMF had no significant impact on lipid levels in patients with either normal or abnormal lipid profiles during one year of treatment. Below are the relevant abstracts from the conference.
EFFICACY AND SAFETY OF TENOFOVIR AMIBUFENAMIDE IN CHRONIC HEPATITIS B VIRUS INFECTION PATIENTS WITH NORMAL ALANINE AMINOTRANSFERASE: A MULTICENTER, OPEN-LABEL, RANDOMIZED CONTROLLED TRIAL
Qing Xie1 Honglian Gui1 Lihong Qu2 Lin Tan3 Piao Hu4 Feng Qian5 Xiaoping Wu6 Yuanwang Qiu7 Sujun Zheng8 Jiaojian Lv9 Yunzhen Shi10 Jun Li11 Yongfang Jiang12 Zhizhen Hu13 Fanru Nie13, 1Ruijin Hospital, Shanghai, China, 2East Hospital, Shanghai, China, 3The Second People's Hospital of Fuyang, 4Hangzhou Xiaoshan 1st People's Hospital, 5The Fifth People's Hospital ofSuzhou,6The 1st Affiliated Hospital of Nanchang, 7Wuxi Fifth People's Hospital, China, 8You 'an Hospital, Beijing, China, 9Lishui People's Hospital, China, 10Dongyang People's Hospital, China, 11Jiangsu Provincial People's Hospital, 12The Second Xiangya Hospital, China, 13Jiangsu Hansoh Pharmaceutical Group Co.,
Background: Antiviral therapy may be beneficial for chronic hepatitis B (CHB) patients (pts) with normal ALT. Tenofovir amibufenamide (TMF) is a novel nucleotide analog reverse transcriptase inhibitor recommended as a first-line treatment for CHB in mainland China. The PROMOTE study aims to evaluate the efficacy and safety of TMF in CHB pts with normal ALT.
Methods: The PROMOTE study (Registration No. NCT05797714) is a multicenter, open-label, randomized controlled trial that enrolled pts with untreated chronic HBV infection, who had normal ALT levels and serum HBV DNA > 20 IU/mL. Pts were randomly assigned 1:1 to group A (oral TMF 25 mg once daily for 48 weeks) or group B (no antiviral treatment). The primary endpoint was the proportion of pts with serum HBV DNA < 20 IU/mL at week 48.
Results: A total of 211 pts were randomized and 193 were included in the full analysis set (FAS), with 93 in group A and 100 in group B. Seven pts in group B had crossover to TMF due to elevated ALT. Baseline characteristics were generally balanced between groups. At week 48, in the FAS, the proportion of pts with HBV DNA < 20 IU/mL in group A was 74.2%, compared to 9.0% in group B. The proportion difference was 65.2% (95% CI: 54.7-75.7%, P<0.001). In the per-protocol set (PPS), the proportion difference was 68.3% (95% CI: 58.0-78.7%, P<0.001), further supporting the better efficacy of group A. In the FAS, the median reduction in HBV DNA at week 48 was 2.63 log10 IU/mL in group A and 0.22 log10 IU/ml in group B, with a significant difference (P<0.001). A greater reduction in HBsAg in group A was observed as compared to group B (0.07 vs. 0.04 log10 IU/mL, P=0.02) at week 48. The findings of these secondary efficacy endpoints in the PPS consistently suggested better efficacy in group A. No significant differences were observed in the changes of serum creatinine (1.00 vs. 1.50 umol/L, P=0.856) and eGFR (-1.60 vs. -1.65 mL/min, P=0.461) from baseline between group A and group B. The change of blood lipid parameters from baseline also showed no statistical significance between two groups (P>0.05 for all).
Conclusion: In conclusion, the PROMOTE study demonstrates the significant clinical benefit of TMF in CHB pts with normal ALT, showing substantial improvement in the proportion of pts with HBV DNA < 20 IU/mL, HBV DNA reduction, HBsAg reduction, with favorable renal and lipids safety. The follow-up of PROMOTE study is ongoing, and the report of long-term TMF treatment is
forthcoming.
Disclosures: Qing Xie,Honglian Gui,Lihong Qu,et al.EFFICACY AND SAFETY OFTENOFOVIR AMIBUFENAMIDE IN CHRONIC HEPATITIS B VIRUS INFECTION PATIENTS WITH NORMAL ALANINE AMINOTRANSFERASE: A MULTICENTER, OPEN-LABEL, RANDOMIZED CONTROLLED TRIAL. AASLD 2024.Abstract No 283.
IMMUNOLOGICAL CORRELATES OF RAPID HBSAG DECLINE IN CHRONIC HBV HEPATITIS PATIENTS UNDERGOING TENOFOVIR AMIBUFENAMIDE TREATMENT
Shue Xiong1 Hang Jia1 Xu Quan1 Bo Liang1 Si Lu1 Hua Wang1 Han Li1 Yi Cheng1 Tian Xiang1 Jia Liu1 Xin Zheng1, 1Union Hospital, Tongji Medical College
Background: While most chronic viral hepatitis B (CHB) patients undergoing Tenofovir Amibufenamide (TMF) antiviral therapy experience a rapid decline in HBV DNA levels, the same is not observed for HBsAg decline in all patients, highlighting unclear immunological mechanisms. This study aims to dynamically observe changes in immunological function and its correlation with clinical indicators during the initial stages of TMF antiviral treatment through a prospective, single-center clinical study.
Methods: A total of 31 CHB patients : Nothing to Dreceiving antiviral treatment were included, comprising 15 HBeAg positive and 16 HBeAg negative individuals. Changes in virological indicators were monitored over 24 weeks postTMF treatment. Peripheral blood samples from 11 HBeAg
positive and 10 HBeAg-negative patients were collected at baseline and at 4, 8, 12, and 24 weeks. Peripheral blood mononuclear cells (PBMCs) were analyzed to detect the phenotypes of B cells, dendritic cells (DCs), monocytes, T cells, and HBV-specific T cell functions.
Results: The study found significantly higher baseline levels of HBVDNA, HBV RNA, and HBsAg in the HBeAg-positive CHB group compared to the HBeAg-negative group. After TMF antiviral treatment, HBV DNA and RNA levels decreased rapidly, particularly within the first 4 weeks, in all CHB patients. Notably, the group of HBeAg-positive hepatitis patients (ALT>2ULN at baseline) exhibited a significant decline in HBsAg levels within the first 4 weeks, followed by prompt ALT normalization. In contrast, the HBsAg levels remained at baseline levels in HBeAg-positive infection patients (ALT<2ULN at baseline) and HBeAgnegative patients. Immunological marker monitoring
revealed elevated frequencies of B cells and CD8 T cells, as well as increased expression of HLA-DR on CD4 T cells in the HBeAg-positive group, both at baseline and during treatment. Additionally, monocyte frequency and the expression levels of CD86, CD80, HLA-DR and PD-L1
on B cells after 4 or 8 weeks TMF antiviral treatment were significantly increased, while the expression levels of CD100 and Foxp3 on CD4 and CD8 T cells decreased after 4 weeks of TMF antiviral treatment. Dynamic analysis of HBV-specific T cell function showed an early increase
of HBsAg-specific CD4+ T cell responses post-TMF therapy, particularly during weeks 4-8, in the group of HBeAg-positive hepatitis patients compare to the group of HBeAg-positive infection patients.
Conclusion: TMF antiviral treatment leads to rapid declines in HBV DNA and RNA levels in CHB patients, with more pronounced HBsAg reduction observed in treatment naïve HBeAgpositive hepatitis patients. This reduction coincides with activation of peripheral B and T cell immune functions, as well as early increased HBsAg-specific CD4+ T cell responses in this group of patients. Our results suggest a potential immunological mechanism underlying TMF's antiviral effect during early treatment stages.
Disclosures:Shue Xiong,Hang Jia,Xu Quan,et al.IMMUNOLOGICAL CORRELATES OF RAPID HBSAG DECLINE IN CHRONIC HBV HEPATITIS PATIENTS UNDERGOING TENOFOVIR AMIBUFENAMIDE TREATMENT.AASLD 2024.Abstract No 271.
EFFECTIVENESS AND SAFETY OF 48-WEEK TENOFOVIR AMIBUFENAMIDE VS TENOFOVIR ALAFENAMIDE FUMARATE FOR PATIENTS WITH CHRONIC HEPATITIS B:A RETROSPECTIVE REAL-WORLD STUDY
Qing-Lei Zeng1 Ru-Yue Chen1 Xue-Yan Lv1, 1The First Affi liatedHospital of ZhengzhouUniversity
Background: Few comparison data are existed on the effectiveness and safety of tenofovir amibufenamide (TMF) vs tenofovir alafenamide fumarate (TAF) for patients with chronic hepatitis B (CHB) in real-world settings. The aim of this study was to evaluate the 48- week real-life effectiveness and safety profiles of TMF vs TAF for patients with CHB.
Methods: This retrospective single-arm study recruited treatment-naive CHB patients who undergone TMF or TAF therapy at 25 mg daily at The First Affiliated Hospital of Zhengzhou University, China, from January 2021 to May 2024. The primary effectiveness outcome was HBV DNA undetectable (less than 20 IU/mL) rate at week 48. The key secondary outcomes were ALT normalization rate, hepatitis B e antigen (HBeAg) seroconversion rate, renal function, renal tubular function parameters, and lipid dynamic levels at week 48.
Results: A total of 130 CHB patients were enrolled, thereinto, 72 and 58 patients were treated with TMF and TAF, respectively . The baseline HBV DNA levels in the TMF and TAF groups were 4.8 ± 2.69 vs 4.5 ± 2.74 log10 IU/mL (p =0.521). At 48 weeks of treatment, the HBV DNA undetectable rates were 81.9% (59/72) vs 84.5% (49/ 58) (p =0.701) in TMF and TAF groups. ALT normalization rates were 83.8% (31/37) vs 75.0% (15/20) (p =0.423), and the HBeAg seroconversion rates were 22.0% (9/41) vs 15.6% (5/32) (p =0.496) in TMF and TAF groups, respectively. In terms of safety, no severe adverse events were occurred and no one discontinued therapy due to adverse events during treatment. Furthermore, there were no significant differences inrenal function and renal tubular function parameters between two groups at 48 weeks of treatment (all p> 0.05); and there were no significant differences were observed in lipid profile parameters between two groups at 48 weeks of treatment (all p> 0.05).
Conclusion: TMF and TAF exhibited similar 48-week effectiveness and safety profiles for CHB patients in real-world settings. Future prospective, long-term validation studies are warranted.
Disclosures: Qing-Lei Zeng,Ru-Yue Chen,Xue-Yan Lv.EFFECTIVENESS AND SAFETY OF 48-WEEK TENOFOVIR AMIBUFENAMIDE VS TENOFOVIR ALAFENAMIDE FUMARATE FOR PATIENTS WITH CHRONIC HEPATITIS B: A RETROSPECTIVE REAL-WORLD STUDY.AASLD 2024. Abstract No 430.
THE IMPACT OF TENOFOVIR AMIBUFENAMIDE (TMF) ON BLOOD LIPIDS DURING THE PROCESS OF ANTI-HEPATITIS B VIRUS TREATMENT - A REAL WORLD PROSPECTIVE STUDY
Ling Yang1 Wenkang Gao1 Huikuan Chu1 Jin Ye1 Fan Du1 Ling Yang2, 1Union hospital, Tongji Medical College, 2Huazhong University of Science and Technology
Background: Tenofovir amibufenamide (TMF), a second-generation of tenofovir, is a widely used antiviral drug for chronic hepatitis B. However, it remains unclear whether long-term use of TMF would affect blood lipid metabolism. As the prevalence of metabolism-related diseases continues to rise, there is an increasingly demand for maintaining appropriate blood lipid levels. Therefore, a real-world prospective study was designed and carried out aiming at clarifying the influence of TMF on blood lipid spectrum by comparing the changes of blood lipid profiles before and after antiviral treatment.
Methods: A total of 209 chronic hepatitis B (CHB) patients with TMF treatment were enrolled in this study.Among which, 19 patients were found to be receiving lipid-lowering medication treatment, and 38 patients are excluded for combining other liver disease and incomplete data. Finally, 89 patients were recorded to have complete data before and after TMF treatment,with 43 patients having normal baseline blood lipids normal group) and 46 patients having disordered blood lipids (abnormal group) before TMF intervention. During the follow-up period, lipid profiles, including total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), were used to analyze the effects of TMF on blood lipids (Using Wilcoxon matched-pairs signed rank test). (ClinicalTrials.gov number,NCT05398393.).
Results: Compared to baseline, the levels of lipid indices after a median follow-up of 370(304~452) days in patients accepting TMF (n =89) were not changed significantly [TC: 4.67 vs. 4.69 (p =0.16),TG: 1.07 vs. 1.04 (p =0.31), HDL-C: 1.27 vs. 1.27(p= 0.25), LDL-C: 3.02 vs. 3.03 (p = 0.41)]. In the abnormal group(n = 46), the changes in blood lipid profiles before and after TMF treatment were not significant, either [ TC: 5.2 vs. 4.98 (p =0.98), TG:1.22 vs.1.19 (p = 0.84), HDL-C: 1.13 vs.1.21 (p =0.59),LDL-C: 3.49 vs. 3.33 (p = 0.89)]. And in the normal group (n =43), the levels of blood spectrums remained relatively stable [TC: 4.29 vs. 4.38 (p = 0.06), TG: 0.92vs. 0.91 (p =0.09), HDL-C: 1.30 vs. 1.32 (p =0.43),LDL-C: 2.54 vs. 2.63 (p = 0.33)].
Conclusion: TMF showed no significantly lipid-raising effect during one year follow-up of antiviral treatment.
Disclosures:Ling Yang,Wenkang Gao,Huikuan Chu et al.THE IMPACT OF TENOFOVIR AMIBUFENAMIDE (TMF) ON BLOOD LIPIDS DURING THE PROCESS OF ANTI-HEPATITIS B VIRUS TREATMENT - A REAL WORLD PROSPECTIVE STUDY.AASLD 2024.Abstract No 247.
