Tenofovir Disoproxil Fumarate

近日，备受瞩目的第34届亚太肝病学会年会（APASL 2025）在北京召开。本次大会上，翰森制药自主研发的中国首个原研口服抗乙型肝炎病毒药物恒沐®（艾米替诺福韦，TMF）20余项学术成果发布，其中2项研究成果入选口头报告，分别为恒沐®Ⅳ期研究5年随访结果及抗病毒治疗免疫学机制研究结果。 IV期研究5年随访结果显示，恒沐®治疗慢性乙型肝炎患者在多个疗效终点，特别是在病毒学反应和HBeAg转阴方面持续为患者带来获益，其中治疗5年累积HBV DNA抑制率高达95%，且HBeAg转阴率达68%，在目前NAs类药物中最高。恒沐®治疗使63%的患者成为功能性治愈优势人群，且5年治疗累积病毒学耐药发生率为0。安全性方面，研究期间未发现新的药物相关不良事件，骨、肾和脂质安全性参数均保持稳定。 抗病毒治疗免疫学机制研究结果显示，恒沐®在慢性HBV感染和复制小鼠模型中均具有明显的抗病毒活性和免疫调节作用，其有可能通过调节T细胞反应和降低病毒载量而治疗慢性HBV感染。从而揭示了恒沐®发挥显著抗病毒疗效（高HBeAg阴转率）的潜在分子免疫学机制。 IV期研究5年随访结果显示，恒沐®治疗慢性乙型肝炎患者在多个疗效终点，特别是在病毒学反应和HBeAg转阴方面持续为患者带来获益，其中治疗5年累积HBV DNA抑制率高达95%，且HBeAg转阴率达68%，在目前NAs类药物中最高。恒沐®治疗使63%的患者成为功能性治愈优势人群，且5年治疗累积病毒学耐药发生率为0。安全性方面，研究期间未发现新的药物相关不良事件，骨、肾和脂质安全性参数均保持稳定。 抗病毒治疗免疫学机制研究结果显示，恒沐®在慢性HBV感染和复制小鼠模型中均具有明显的抗病毒活性和免疫调节作用，其有可能通过调节T细胞反应和降低病毒载量而治疗慢性HBV感染。从而揭示了恒沐®发挥显著抗病毒疗效（高HBeAg阴转率）的潜在分子免疫学机制。 以下为两项口头报告具体内容： 口头报告1 艾米替诺福韦治疗慢性乙型肝炎5年疗效和安全性[1] 报告专家：刘智泓（南方医科大学南方医院） 摘要编号：OP0155 恒沐®(TMF)是替诺福韦的一种新型前药，在中国大陆广泛用于治疗慢性乙型肝炎（CHB）。先前的Ⅲ期注册研究（NCT03903796）已经确定了TMF在抗病毒疗效上非劣于富马酸替诺福韦二吡呋酯（TDF），同时显示出更高的丙氨酸转氨酶（ALT）复常率和改善的骨骼和肾脏安全性。这项Ⅳ期研究进一步展示了TMF的长期疗效和安全性。 【研究方法】 完成TMFⅢ期注册试验的受试者入组该Ⅳ期研究，所有受试者继续每天口服TMF25mg。本次中期分析的主要疗效终点是第5年血清HBV DNA水平低于中心实验室检测下限的参与者比例。 【研究结果】 总共有639例（63.8%）参与者入组， 589例患者纳入符合方案集（PPS）分析，其中包含TMF治疗组399例，TDF转换TMF组（TDF-TMF）190例，两组的患者特征在基线上（第3年）分布均衡。至第5年，TMF组和TDF-TMF组达到HBV DNA <20 IU/mL的比例分别为95.2%和94.1%，比第3年时分别提高了5.5%和7.3%。两组中分别有91.9%和91.5%的患者达到HBV DNA <10 IU/mL。整个研究期间，HBeAg转阴率不断增加，第5年时TMF组和TDF-TMF组的HBeAg转阴率分别达到68.0%和63.4%。同时，第5年TMF组累计有24.8%的患者实现HBeAg血清学转换。5年期间两组功能性治愈（HBsAg<3000 IU/mL）优势人群比例均不断升高，至第5年，总体人群中功能性治愈优势人群占比达63%。TMF持续治疗5年期间的累积病毒学耐药率为0。在ALT复常方面，TMF治疗使得TDF-TMF组患者的ALT复常率在第5年继续升高，基于AASLD标准相比第3年提高了4.6%。经过TMF的转换治疗，TDF对患者的肝损伤得到了逆转，至第5年时，两组的ALT复常率已无显著性差异。安全性方面，第3年至第5年治疗期间总体安全性良好，严重不良事件（SAE）发生率低（2.7%）。至第5年时，53.9%的患者腰椎骨密度Z值评分显示增加，TMF组和TDF-TMF组之间无明显差异。在总体人群中，估算肾小球滤过率（eGFR）<60 ml/min/1.73 m2的累积发生率在5年期间一直维持在较低水平（0.0%~0.5%），总胆固醇/高密度脂蛋白胆固醇（TC/HDL）比值也保持稳定，体重仅有轻微增加。 【研究结论】 恒沐®治疗慢性乙型肝炎患者5年疗效和安全性良好。无论是TMF持续治疗组还是TDF转换TMF治疗组，在接受TMF继续治疗后均维持高病毒学应答率，甚至使绝大部分（>90%）患者实现了HBV DNA<10 IU/mL。长期TMF治疗还持续提高了HBeAg转阴和血清学转换的患者比例。此外，骨、肾和脂质安全性参数在研究期间维持稳定。该研究仍在进行中，未来还将有进一步的随访结果。 口头报告2 艾米替诺福韦在慢性HBV复制小鼠模型中的抗病毒和免疫调节作用的评价[2] 报告专家：刘嘉（华中科技大学同济医学院附属协和医院） 摘要编号：OP0312 本研究在两种不同的小鼠模型中研究了艾米替诺福韦对慢性乙型肝炎病毒（HBV）感染的抗病毒疗效和免疫调节作用。 【研究方法】 采用两种小鼠模型：(1)通过尾静脉注射rAAV8-HBV1.3重组病毒建立rAAV8-HBV1.3慢性感染模型；(2)通过流体动力学注射HBV表达质粒BPS建立BPS HDI慢性复制模型。小鼠在HBV感染后14至27天口服TMF、恩替卡韦（ETV）或富马酸替诺福韦二吡呋酯（TDF）。监测血清HBsAg、HBeAg、HBsAb、HBeAb和HBV DNA水平。在感染乙肝病毒后第28天，分离肝脏浸润淋巴细胞，用流式细胞术分析T细胞活化、分化和HBV特异性T细胞反应。 【研究结果】 在rAAV8-HBV1.3感染小鼠模型中，TMF治疗显著降低血清HBV DNA水平，与ETV和TDF治疗相当。TMF还增加了活化的CD69+CD4+和CD8+T细胞、前体细胞效应CD4+和CD8+T细胞以及分泌IFN-γ的CD4+T细胞的频率。在BPS HDI模型中，TMF治疗同样降低了血清HBV DNA水平，增加了前体效应CD4+T细胞、分泌IFN-γ和IL-2的CD4+T细胞和分泌IFN-γ的CD8+T细胞的频率。此外，TMF治疗显示肝脏中HBcAg特异性CD8+T细胞具有增加的趋势。 【研究结论】 恒沐®在慢性HBV感染和复制小鼠模型中均表现出显著的抗病毒活性和免疫调节作用。这些发现表明TMF有可能通过调节T细胞反应和降低病毒载量而治疗慢性HBV感染。 其中，一项系统综述与网络Meta分析结果显示，在四种新一代NAs类药物【TAF、TMF、BSV和PDV】中，恒沐®在ALT复常、延缓肝纤维化进展方面更具优势，且骨骼、肾脏安全性最佳[3]。一项回顾性研究首次证明了恒沐®治疗慢乙肝孕妇具有良好的母婴安全性和疗效，结合标准的乙肝免疫接种，可成功预防HBV母婴传播[4]。另一项回顾性真实世界研究首次证实了恒沐®治疗HBV相关肝细胞癌（HCC）患者具有良好的有效性和安全性，且相比ETV具有更高的ALT复常率和更佳的血脂状况[5]。两项针对HBV相关慢加急性肝衰竭（HBV-ACLF）患者的研究显示，恒沐®的疗效与ETV、TAF相当[6、7]。多项研究显示，恒沐®并不影响患者的糖脂代谢[8、10]。 这些研究从不同角度证实了恒沐®具有显著的抗病毒疗效和安全性优势，也为慢性乙型肝炎（CHB）患者的临床优化治疗提供了循证依据参考。 参考文献： [1]Jinlin Hou,et al.5-Year Efficacy and Safety of Tenofovir Amibufenamide in Chronic Hepatitis B Patients.APASL 2025.OP0155 [2]Jia Liu,et al.Evaluation of Antiviral and Immunomodulatory Effects of Tenofovir amibufenamide in Chronic HBV-replication Mouse Models. APASL 2025.OP0312 [3]Zhihong Liu,et al. New generation nucleotide analogues in treating chronic hepatitis B within Asian population: a systematic review and network meta analysis of randomized controlled trials. APASL 2025.EP0154 [4]Ruyue Chen,et al. Safety and Effectiveness of Tenofovir Amibufenamide for Pregnant Women with Chronic Hepatitis B. APASL 2025.PP0187 [5]Yuehang Wang,et al. Effectiveness and Safety of 48-Week Tenofovir Amibufenamide in Patients with Hepatitis B Virus-Related Hepatocellular Carcinoma: A Retrospective Real-World Study. APASL 2025.PP0245 [6]Jing Cui,et al. Analysis of the Short-term Efficacy and Safety of Tenofovir Amibufenamide in the Treatment of Patients with HBV-related Acute-on-chronic Liver Failure. APASL 2025.PP0853 [7]Xiao Chuan Diao,et al.Comparative efficacy and safety of tenofovir amibufenamide vs tenofovir alafenamide and entecavir in the hepatitis B virus related acute-on-chronic liver failure patients: A single-centre retrospective study. APASL 2025.PP0192 [8]Jie Li,et al. Evaluation of the therapeutic efficacy of alafenamide fumarate and tenofovir amibufenamide in the treatment of chronic hepatitis B patients with concomitant hyperlipidemia. APASL 2025.EP0120 [9]JUN LI,et al.A real-world study of the efficacy of tenofovir amibufenamide (TMF) in the treatment of patients with chronic hepatitis B and its effect on blood glucose and lipid levels. APASL 2025.PP0189 [10]Jishen Zhang,et al. The effect of tenofovir amibufenamide on lipid metabolism in patients with chronic hepatitis B is less than that of tenofovir alafenamide. APASL 2025.PP0196 声明： 1、本公告仅供医疗卫生专业人士参阅，非广告用途。 2、翰森制药不推荐任何未获批药品使用和/或未获批适应症用药，亦不对任何药品和/或适应症作推荐。 3、本公告中涉及的信息仅供参考，请遵从医生或其他医疗卫生专业人士的意见或指导。医疗卫生专业人士作出的任何与治疗有关的决定应根据患者的具体情况并遵照药品说明书。 4、如需了解公司任何产品、医疗或疾病的相关信息，请务必咨询医疗卫生专业人士。 前瞻性说明 本新闻稿旨在提供关于翰森制药集团有限公司及其附属公司（包括其子公司，统称为“翰森制药”）的信息。它不构成对翰森制药或任何投资建议的信息披露。 本新闻稿包含的信息可能包括与翰森制药业务和产品前景、计划、信念、预期和策略相关的前瞻性声明。这些声明是基于推测性假设的预测，并不保证未来的表现。它们受到诸如科学、商业、政治、经济、财务、法律因素以及竞争环境和社会条件等风险和不确定性的影响，这些因素很多都是翰森制药无法控制且难以预测的，因此实际结果可能与此处所述有显著差异，且过去的证券价格趋势不应作为未来行情的指导。因此，投资者在使用这些信息进行投资决策时应谨慎行事。“致力于”“预期”“相信”“预测”“意图”“预计”“可能”“将”“应该”“计划”“继续”“目标”“考虑”“估计”“指导”“潜在”“追求”以及于任何未来计划、行动或事件的讨论中使用的类似词语和术语，均表示前瞻性声明。 翰森制药不承诺或保证前瞻性信息的准确性、及时性或完整性，并且不承担更新或修订这些前瞻性声明的义务。无论是翰森制药还是其任何董事、员工或代理人，均不对任何证明不准确或无法实现的前瞻性声明负责，也不对因依赖本新闻稿中提供的信息而产生的任何损失或损害负责，包括但不限于直接、偶然、间接或惩罚性的损害。

– Long-Term Outcomes Reinforce the High Efficacy of Biktarvy ® in People with HIV and HBV Coinfection – – Investigational Long-Acting, Twice-Yearly Treatment Regimen of Lenacapavir and Broadly Neutralizing Antibodies (bNAbs) Meets Primary Endpoint in Phase 2 Study and Gains Breakthrough Therapy Designation – – Late-Breaker Oral Presentation of Phase 2 Results from the First HIV Cure Clinical Trial Conducted in South Africa – FOSTER CITY, CA, USA I March 12, 2025 I Gilead Sciences, Inc. (Nasdaq: GILD) today announced the presentation of late-breaking data and multiple oral presentations from its innovative HIV treatment portfolio and pipeline at the Conference on Retroviruses and Opportunistic Infections (CROI 2025). The new findings reflect a transformative portfolio and a rapidly advancing forward-looking pipeline focused on expanding choices and enhancing outcomes for those with HIV, while continuing to reach towards a cure. “Gilead is fueling the next wave of innovation in HIV to help end the epidemic globally,” said Jared Baeten, MD, PhD, Senior Vice President, Virology Therapeutic Area Head. “Our contributions to CROI spotlight our dedication to scientific discovery, reflect our commitment to addressing the diverse treatment needs and preferences of communities affected by HIV and underscore the vital importance of catalyzing research reaching towards a cure.” Biktarvy Demonstrates High Rates of Viral Suppression in People with HIV/HBV Coinfection ALLIANCE ( NCT03547908 ) is an ongoing Phase 3 study evaluating Biktarvy versus dolutegravir 50 mg (DTG) + emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg, F/TDF, DTG+F/TDF, in adults with HIV-1/HBV co-infection initiating treatment. The ALLIANCE trial is the first randomized clinical trial of TAF- vs TDF-based regimens in treatment naïve adults with HIV/HBV coinfection. Its goal is to evaluate treatment regimens that may effectively suppress both HIV and HBV. Previously reported results demonstrated the efficacy of both antiretroviral regimens. New outcomes were presented at CROI. Week 48 outcomes from the open-label extension phase following the 96-week randomized phase reported on the longer-term efficacy and safety of the investigational use of Biktarvy in adults with HIV/HBV coinfection initiating treatment. The newly presented data shows that Biktarvy maintained high rates of HIV-1 (95.4%) and HBV (86.6%) virologic suppression, defined as HIV RNA <50 copies/ mL and HBV DNA <29 IU/ mL, respectively, in participants (n=89) following a switch to Biktarvy after 96 weeks of treatment with DTG+ F/TDF. Study drug-related treatment-emergent adverse events (TEAEs) were reported in 19% of participants and most were mild to moderate, with zero discontinuations due to TEAEs. The most commonly reported study drug–related TEAEs were weight gain (9%) and low-density lipoprotein (LDL) cholesterol increased (3%). These data demonstrate the high rates of viral suppression by Biktarvy in adults with both HIV-1 and HBV switching their treatment to Biktarvy. The use of Biktarvy in individuals with HIV/HBV co-infection is investigational and the safety and efficacy of this use have not been established. Breakthrough Therapy Designation Awarded to Long-Acting, Twice-Yearly Investigational Treatment Combination Regimen of Lenacapavir and Broadly Neutralizing Antibodies (bNAbs) In January 2025, the FDA granted lenacapavir (LEN) with bNAbs (teropavimab [GS-5423, TAB] and zinlirvimab [GS-2872, ZAB]) Breakthrough Therapy Designation, which is intended to expedite the development of new drugs that may demonstrate substantial improvement over available therapy. LEN+TAB+ZAB (LTZ) harbors the potential to be the first long-acting combination treatment regimen with twice-yearly dosing. At CROI 2025, the primary results of a Phase 2 study evaluating the investigational combination of LTZ were presented during an oral session and featured in the press program; those data announced at CROI confirm previously presented Phase 1b results. The Phase 2 ( NCT05729568 ) open-label study from Gilead’s long-acting treatment pipeline evaluated the treatment response of participants receiving the investigational combination of LTZ. Efficacy and safety results were evaluated when virologically suppressed adults switched to LTZ every 6 months versus staying on stable baseline oral antiretroviral regimen. The study met its primary endpoint, which is the proportion of participants with HIV-1 RNA ≥ 50 copies/mL at Week 26 as determined by the US FDA-defined snapshot algorithm. The Week 26 data demonstrated the high efficacy of the LTZ regimen, with 96% (n=51 of 53) of participants who received LTZ and 96% (n=26 of 27) who received SBR remained virologically suppressed. CD4 cell counts also increased from baseline to week 26 in both groups, with a mean change of +23/μL (n=143) with LTZ and +69/μL (n=203) with SBR. The most common AEs with LTZ were injection site reactions related to subcutaneous LEN administration. There were no serious adverse events (AEs) related to LTZ; there were no infusion reactions related to TAB or ZAB. One participant in the SBR arm discontinued the study due to a serious treatment-related AE. Teropavimab and zinlirvimab are investigational compounds. The use of these compounds in combination with lenacapavir are investigational. They are not approved by the U.S. Food and Drug Administration or any other regulatory authority for any use, alone or in combination with lenacapavir. Their safety and efficacy are unknown. The use of lenacapavir in virologically suppressed people with HIV is investigational and the safety and efficacy of this use have not been established. Landmark HIV Cure Clinical Trial Conducted in South Africa Results from the first HIV cure trial to be conducted in South Africa, sponsored by Gilead, demonstrated that complex cure studies can be successfully conducted, alongside community, in resource-limited settings where great unmet need exists. As part of Gilead’s efforts to find a cure for HIV, the Phase 2a GS-US-382-5445 trial ( NCT05281510 ) enrolled 20 South African cisgender women from the FRESH (Females Rising through Education, Support, and Health) cohort who had received antiretroviral therapy (ART) soon after acquiring HIV and were virologically suppressed for at least 12 months. Participants received up to 10 oral doses of Gilead’s investigational TLR7 agonist, vesatolimod, every 2 weeks starting on day 0, plus IV infusions of broadly neutralizing antibodies (bNAbs) VRC07-523LS and CAP256V2LS, provided by the National Institutes of Health (NIH), on day 7. Participants began an analytical treatment interruption (ATI) on Day 35 and remained off ART until Week 48, or until they met restart criteria. Participants who reached week 48 without meeting ART restart criteria had the option of remaining off ART through the end of study follow-up at Week 60. Results presented at CROI showed the treatment combination was generally well-tolerated with no treatment-related serious adverse events (TEAEs) reported. The most common study TEAEs were infusion-related reactions (n = 18; 16 grade 1, 2 grade 2). Seventy percent of participants (n=14) met ART restart criteria. Thirty percent (n=6) remained off ART through Week 48, of which 4 remained off ART through Week 60. While the data suggest that the trial regimen alone is not sufficient as an HIV cure regimen, the mechanistic learnings will inform the development of future cure approaches. There is currently no cure for HIV or AIDS. Vesatolimod, VRC07-523LS and CAP256V2LS are investigational compounds. They are not approved by the U.S. Food and Drug Administration or any other regulatory authority for any use, alone or in combination. Their safety and efficacy are unknown. Please see below for U.S. Indications and Important Safety Information, including Boxed Warning , for Biktarvy. About Lenacapavir Lenacapavir is approved in multiple countries for the treatment of adults with multi-drug resistant HIV in combination with other antiretrovirals. The use of lenacapavir for HIV prevention is investigational and the safety and efficacy of lenacapavir for this use have not been established. The multi-stage mechanism of action of lenacapavir is distinguishable from other currently approved classes of antiviral agents. While most antivirals act on just one stage of viral replication, lenacapavir is designed to inhibit HIV at multiple stages of its lifecycle and has no known cross resistance exhibited in vitro to other existing drug classes. Lenacapavir is being evaluated as a long-acting option in multiple ongoing and planned early and late-stage clinical studies in Gilead’s HIV prevention and treatment research program. Lenacapavir is being developed as a foundation for potential future HIV therapies with the goal of offering both long-acting oral and injectable options with several dosing frequencies, in combination or as a mono agent, that help address individual needs and preferences of people and communities affected by HIV. Science Magazine named lenacapavir its 2024 “Breakthrough of the Year.” About Biktarvy Biktarvy is a complete HIV treatment that combines three powerful medicines to form the smallest 3-drug, integrase strand transfer inhibitor (INSTI)-based single-tablet regimen (STR) available, offering simple once-daily dosing with or without food, with a limited drug interaction potential and a high barrier to resistance. Biktarvy combines the novel, unboosted INSTI bictegravir with the F/TAF backbone. Biktarvy is a complete STR and should not be taken with other HIV medicines. U.S. Indication for Biktarvy Biktarvy (bictegravir 50 mg/emtricitabine 200 mg/tenofovir alafenamide 25 mg) is indicated as a complete regimen for the treatment of HIV-1 infection in adults and pediatric patients weighing at least 14 kg who have no antiretroviral (ARV) treatment history or to replace the current ARV regimen in those who are virologically-suppressed (HIV-1 RNA <50 copies per mL) on a stable ARV regimen with no known or suspected substitutions associated with resistance to bictegravir or tenofovir. About Gilead HIV Gilead Sciences, Inc. is a biopharmaceutical company that has pursued and achieved breakthroughs in medicine for more than three decades, with the goal of creating a healthier world for all people. The company is committed to advancing innovative medicines to prevent and treat life-threatening diseases, including HIV, viral hepatitis, COVID-19, and cancer. Gilead operates in more than 35 countries worldwide, with headquarters in Foster City, California. For more than 35 years, Gilead has been a leading innovator in the field of HIV, driving advances in treatment, prevention and cure research. Gilead researchers have developed 12 HIV medications , including the first single-tablet regimen to treat HIV, the first antiretroviral for pre-exposure prophylaxis (PrEP) to help reduce new HIV infections, and the first long-acting injectable HIV treatment medication administered twice-yearly. Our advances in medical research have helped to transform HIV into a treatable, preventable, chronic condition for millions of people. Gilead is committed to continued scientific innovation to provide solutions for the evolving needs of people affected by HIV around the world. Through partnerships , collaborations and charitable giving, the company also aims to improve education, expand access and address barriers to care, with the goal of ending the HIV epidemic for everyone, everywhere. Gilead has been repeatedly recognized as one of the top two leading philanthropic funders of HIV-related programs in a report released by Funders Concerned About AIDS. SOURCE: Gilead Sciences