Real World Evidence Study of the Effectiveness of Paritaprevir/r - Ombitasvir, + Dasabuvir Without Ribavirin in Patients With Chronic HCV Gt1b Infection and Compensated Liver Cirrhosis in the RussIan FederaTion- An ObseRvational, MultI-CeNter Study (CITRIN)

This prospective, multi-center, observational study is designed to assess the real world effectiveness of paritaprevir/r - ombitasvir with dasabuvir (3DAA [direct-acting antiviral agent] ABBVIE REGIMEN) without ribavirin (RBV) and to describe baseline characteristics of participants with chronic hepatitis C virus (HCV) genotype 1b (GT1b) infection and compensated liver cirrhosis in Russia.

开始日期2017-03-20

申办/合作机构

AbbVie, Inc.

NCT03002818

/ CompletedN/A

Quality of Life Measurement Using Wrist Actigraphy in HCV Genotype 1 Infected, Treatment naïve Patients Suffering From Fatigue and Receiving Ombitasvir, Paritaprevir, and Ritonavir Tablets and Dasabuvir Tablets (Viekirax®/Exviera®; 3D Regimen): The HEMATITE Study

This is an observational, prospective, open-label, single-arm, multicenter, real-life study designed to observe the impact of paritaprevir/ritonavir/ombitasvir with dasabuvir regimen (Viekirax®/Exviera®, 3D regimen) on total daytime physical activity and fatigue in participants with HCV GT1.

开始日期2017-03-01

申办/合作机构

AbbVie, Inc.

JPRN-UMIN000026640

/ CompletedN/AIIT

Predictive factors associated with virological response in Ombitasvir/Paritaprevir/Ritonavir/Ribavirin combination therapy for genotype2a infected chronic hepatitis C patients - Virological response in Ombitasvir/Paritaprevir/Ritonavir/Ribavirin combination therapy for genotype2a infected chronic hepatitis C patients

开始日期2017-01-16

申办/合作机构-

100 项与奥比他韦相关的临床结果

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100 项与奥比他韦相关的转化医学

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100 项与奥比他韦相关的专利（医药）

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1,033

项与奥比他韦相关的文献（医药）

2025-08-01·JOURNAL OF PHARMACEUTICAL SCIENCES

Investigating the effect of permeation enhancers on oral absorption of a BCS IV compound, ombitasvir, utilizing animal models

Article

作者: Hanouch, Layan ; Borchardt, Thomas ; Gignac, Nathan ; Indulkar, Anura S ; Marsh, Kennan

Discovery of complex biological targets and novel treatment modalities have led to an increase in the number of compounds with poor permeability. Generally, formulation design and development are primarily focused on overcoming poor solubility. Improving oral bioavailability by utilizing permeation enhancers for poorly permeable new chemical entities (NCEs) has not been widely explored. Therefore, in this work the effect of permeation enhancers on a poorly soluble and poorly permeable compound, ombitasvir (OBT), was investigated. Structurally diverse permeation enhancers (PEs) with good safety profile-labrasol® ALF, lauroyl L- and palmitoyl L-carnitine, salcaprozoate sodium (SNAC), and sodium caprate-were tested. To study the impact of solid form and formulation, OBT was dosed as crystal form and as amorphous formulations. To avoid the influence of preclinical in vitro/ex vivo method artifacts on data interpretation, studies were conducted in whole animal models (rat and dog). OBT was dosed at 2 mg/kg and PEs were dosed at 20 mg/kg by peroral route. In rats, OBT was administered as an amorphous colloidal suspension. Only the carnitines showed meaningful enhancement (∼2X) in oral bioavailability. In dogs, OBT was dosed in enteric capsules as crystal form, a slow dissolving 15 % drug load (DL) amorphous solid dispersion (ASD) that slowly reached amorphous solubility, and a rapidly dissolving 5 % DL ASD that reached amorphous solubility and formed amorphous nanoprecipitates, with and without PEs. OBT was not detected in the blood upon dosing of neat crystalline solid. However, when co-dosed with PEs significantly high oral bioavailability (11-17 %) was observed. 15 % DL ASD alone showed a meaningful increase in oral bioavailability (∼4 %) relative to the crystal form; and combination with PEs further increased the bioavailability by 2-5 fold. All the PEs showed enhancement in oral bioavailability when combined with the crystal form and 15 % DL ASD. The enhancement in bioavailability due to SNAC was attributed to dissolution rate enhancement whereas, that due to lauroyl L-carnitine and labrasol was attributed to both dissolution and permeability enhancement. 5 % DL ASD by itself increased the oral bioavailability to ∼8 % which was attributed to its rapid dissolution. A massive increase in the oral bioavailability to 78 % (∼10-fold enhancement) was observed with lauroyl L-carnitine. In contrast to the crystal form and 15 % DL ASD groups, other PEs, were found to be ineffective when combined with the 5 % DL ASD. Physicochemical characterization including solubility determination in presence of PEs, dissolution performance of the forms/formulations and particle size distribution of the amorphous precipitated phase (for 5 % DL ASD) in presence of PEs was performed to understand in vivo results. It was concluded that the dissolution rate of the form/formulation, the amount of drug concomitantly available with PE at the site of absorption, the association of PE with the precipitated amorphous phase and the particle size of this phase impacts the overall performance of PE towards improving oral bioavailability. The results of this study present promising approaches to formulate BCS IV compounds.

2025-04-13·Cureus Journal of Medical Science

The Impact of Organic Anion-Transporting Polypeptide (OATP) Variants on the Side Effects of Direct-Acting Antivirals in Hepatitis C Patients

Article

作者: Altintas, Zuhal ; Altintas, Engin

Background Organic anion-transporting polypeptides (OATPs) are responsible for the cellular uptake of a broad range of endogenous compounds and xenobiotics in multiple tissues. The aim of our study was to determine whether variations in OATP1B1 and OATP1B3 affect the side effects experienced by hepatitis C patients treated with direct-acting antivirals (DAAs). Methods This study included 199 hepatitis C patients treated with DAAs. Ledipasvir/sofosbuvir or ombitasvir/paritaprevir/ritonavir ± dasabuvir and 162 control individuals without hepatitis C. Treatment-related side effects were recorded. The OATP1B1 gene variations c.388A>G and c.521T>C and the OATP1B3 gene variations c.334T>G and c.699G>A were analyzed via the polymerase chain reaction-restriction fragment length polymorphism method. Allele/genotype combinations of OATP1B1 and OATP1B3 haplotypes were evaluated. Results Side effects were observed in 53 (26.6%) of 199 hepatitis C patients. There were skin mucosal lesions in 19 patients (36%), fatigue in 18 patients (34%), pruritus in 11 patients (20.5%), and other in five patients (9.5%). There was a significant relationship between the c.334T>G variant and side effects (p = 0.030). The frequency distribution of the c.334T>G variant was in Hardy-Weinberg equilibrium. The frequencies of the patient group and the control group were 65.3% and 63%, respectively. We found a significant difference between the patient and control groups in terms of the haplotype ratios of c.388A>G and c.521T>C (p = 0.036). Conclusions We found a significant relationship between the c.334T>G variant in OATP1B3 and DAA-related side effects in hepatitis C patients.

2025-02-01·EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES

Pyrrolidine SS13 induces oxidative stress and autophagy-mediated cell death in colorectal cancer cells

Article

作者: Majirska, Monika ; Keselakova, Alexandra ; Pilatova, Martina Bago ; Kello, Martin ; Martinkova, Miroslava ; Mirossay, Andrej ; Nosalova, Natalia ; Fabianova, Dominika

INTRODUCTION:

Pyrrolidines, nitrogenous organic compounds, are among the most intensively studied agents because of their antibacterial, antiviral, neurological, and promising antitumor effects. Moreover, many medicinal drugs contain pyrrolidine moiety such as sunitinib (anticancer drug), telaprevir and ombitasvir (antiviral drugs) or ramipril (antihypertensive drug).

RATIONALE OF THE STUDY:

Based on the pro-apoptotic effect of pyrrolidine SS13, this study focuses on the pro-oxidative properties of the tested pyrrolidine SS13 on colorectal cancer cells to deepen the understanding of its mechanisms of action.

RESEARCH HYPOTHESIS:

We hypothesize that SS13 induces oxidative stress and autophagy activation in HCT116 and Caco-2 cell lines, thus contributing to antiproliferative effects.

METHODS:

Flow cytometry, western blot, fluorescence microscopy and qRT-PCR were used to evaluate the effect of pyrrolidine SS13.

CONCLUSION AND FUTURE DIRECTIONS:

Pyrrolidine SS13 induced oxidative stress through the accumulation of reactive oxygen and nitrogen species in both cell lines and the modulation of both superoxide dismutase isoenzymes (SOD1, SOD2). Oxidative stress was also associated with the activation of DNA damage response system and modulation of stress/survival pathways. We demonstrated for the first time that pyrrolidine SS13 is involved in the induction of autophagy accompanied by increased levels of autophagic markers (p-AMPK, p-ULK, LC3I/II and ATG7) and a significant decrease in p62 protein levels in both cell lines. Finally, chloroquine, an inhibitor of autophagy, enhanced cell survival and suppressed the cytotoxic effect of SS13 in HCT116 and Caco-2 cells, indicating that SS13 contributes to autophagy-mediated cell death. Taken together, our results suggest that oxidative stress and autophagy participate in the antiproliferative effect of pyrrolidine SS13 on colorectal cancer cells. Further research using primary cell cultures obtained from different animal tissues as well as performing in vivo experiments is needed to understand these processes in detail and to investigate the potential therapeutic application of new pyrrolidine derivatives.

项与奥比他韦相关的新闻（医药）

2025-02-06

·化学经纬

书籍分享||新药化学全合成路线手册

内容介绍本书归纳和综述了新药的化学合成路线。覆盖范围为近5年美国FDA批准上市的新分子实体药共109个。针对每一个药物，本书给出了药物简介，药物化学结构信息，产品上市信息，药品专利保护和市场独占权保护信息，化学全合成路线和参考文献等。这些合成路线大多是目前制药工业中正在使用的化学合成工艺，有较高的实用性和学术价值。对参与反应的起始原料、中间体、反应产物都给出了详细的化学结构。每一步化学合成反应都给出了重要的化学试剂、催化剂、所使用的溶剂、合成反应条件及文献出处等。本书的特点是：作者从浩如烟海的科技文献中，精心挑选出最新、最有实用价值的合成方法，汇编成化学合成路线图，内容简洁，深入浅出，逻辑性强，容易理解，以最少的篇幅表达最多的技术信息，可帮助读者很快找到他们需要的药物合成方法及最可靠的原始科学论文。读者对象： 1.任何从事与化学合成、药物合成、精细化工相关专业的科研人员、企业管理人员。 2.有机化学专业、药学专业、生物制药专业等大专院校的高年级学生、研究生、教师及科研人员。 3.从事客户委托的药物原料与药物中间体合成的科研人员、企业管理人员。编辑推荐对于制药企业而言,一个好的药物全合成路线, 可以大大缩短生产周期,简化生产工艺,降低生产成本,节约能源,减少或消除对环境的化学污染与排放。本书为了顺应我国近年来生物制药及医药工业飞速发展的潮流编写的，详细介绍了近五年美国FDA批准上市的所有（109个）新分子实体药的化学全合成路线。这些全合成路线多数是国外制药厂目前正在使用的工艺，其经济效益及社会效益都是极为显著，因此本书既有较高的科学价值又有很大的实用性。作者简介陈清奇，旅美药学家和化学家，担任美国MedKoo生物医药科研公司总裁，同时兼任美国数家生物制药公司的技术顾问，中国国内数个大学的客座教授。研究领域为药物化学，纳米医学体外诊断技术。书籍目录 Abiraterone Acetate（醋酸阿比特龙）001 Aclidinium Bromide（阿克利溴铵）006 Afatinib（阿法替尼）009 Alcaftadine（阿卡他定）014 Alogliptin（阿格列汀）017 Apixaban（阿哌沙班）022 Apremilast（阿普斯特）028 Avanafil（阿伐那非）033 Axitinib（阿西替尼）038 Azilsartan Kamedoxomil（阿齐沙坦酯钾盐）044 Bazedoxifene（巴多昔芬）048 Bedaquiline（贝达喹啉）053 Belinostat（贝利司他）060 Boceprevir（波西普韦）064 Bosutinib（博舒替尼）071 Cabozantinib（卡博替尼）075 Canagliflozin（卡格列净）078 Carfilzomib（卡非佐米）083 Ceftaroline Fosamil（头孢洛林酯）087 Ceftolozane（噻呋特啰嗪）094 Ceritinib（色瑞替尼）098 Clobazam（氯巴占）101 Cobicistat（可比司他）104 Crizotinib（克里唑蒂尼）112 Dabigatran Etexilate Mesylate（甲磺酸达比加群酯）118 Dabrafenib（达拉菲尼）123 Dapagliflozin（达格列净）127 Dasabuvir（达沙布韦）132 Deferiprone（去铁酮）136 Dienogest（地诺孕素）138 Dolutegravir（度鲁特韦）141 Droxidopa（屈昔多巴）145 Efinaconazole（艾氟康唑）149 Eliglustat（依利格鲁司特）152 Elvitegravir（埃替格韦）155 Empagliflozin（依帕列净）161 Enzalutamide（恩杂鲁胺）166 Eribulin Mesylate（甲磺酸艾日布林）168 Eslicarbazepine Acetate（艾利西平醋酸酯）175 Estradiol Valerate（雌二醇戊酸酯）180 Ezogabine（依佐加滨）185 Finafloxacin（非那沙星）193 Fingolimod Hydrochloride（盐酸芬戈莫德）197 Florbetapir F 18（氟比他匹）205 Flutemetamol F 18（富特米他）211 Gabapentin Enacarbil（加巴喷丁恩那卡比）214 Gadobutrol（钆布醇）218 Gadoterate Meglumine（钆特酸葡甲胺）224 Ibrutinib（依鲁替尼）227 Icatibant（艾替班特）232 Idelalisib（艾代拉里斯）234 Indacaterol （茚达特罗）236 Ingenol Mebutate（巨大戟醇甲基丁烯酸酯）240 Ioflupane 123I（碘[123I]氟潘）242 Ivacaftor（依瓦卡特）247 Ledipasvir（雷迪帕韦）250 Linaclotide（利那洛肽）259 Linagliptin（利拉利汀）261 Lomitapide（洛美他派）267 Lorcaserin（氯卡色林）270 Lucinactant（芦西纳坦）274 Luliconazole（卢立康唑）276 Lurasidone（鲁拉西酮）279 Macitentan（马西替坦）283 Miltefosine（米替福新）286 Mipomersen Sodium（米泊美生钠）290 Mirabegron（米拉贝隆）292 Naloxegol（纳罗克格）296 Netupitant（奈妥吡坦）299 Nintedanib（尼达尼布）303 Olaparib（奥拉帕尼）307 Olodaterol（奥达特罗）311 Omacetaxine Mepesuccinate（高三尖杉酯碱）315 Ombitasvir（艾姆伯韦）319 Ospemifene（奥培米芬）323 Paritaprevir（帕瑞它韦）327 Pasireotide（帕瑞肽）331 Peramivir（帕拉米韦）333 Perampanel（吡仑帕奈）337 Pirfenidone（吡非尼酮）343 Pomalidomide（泊马度胺）345 Ponatinib（泊那替尼）351 Regorafenib（瑞戈非尼）355 Rilpivirine（利匹韦林）357 Riociguat（利奥西呱）366 Rivaroxaban（利伐沙班）370 Roflumilast（罗氟司特）378 Ruxolitinib（鲁索替尼）384 Simeprevir（司美匹韦）388 Sofosbuvir（索非布韦）396 Suvorexant（苏沃雷生）401 Tafluprost（他氟前列腺素）405 Tasimelteon（他司美琼）409 Tavaborole（它瓦波罗）413 Tedizolid Phosphate（磷酸特地唑胺）415 Telaprevir（替拉瑞韦）418 Teriflunomide（特立氟胺）426 Ticagrelor（替格瑞洛）430 Tofacitinib（托法替尼）438 Trametinib（曲美替尼）443 Umeclidinium（芜地溴铵）447 Vandetanib（凡德他尼）450 Vemurafenib（威罗菲尼）456 Vilanterol（维兰特罗）460 Vilazodone Hydrochloride（盐酸维拉佐酮）463 Vismodegib（维莫德吉）468 Vorapaxar（沃拉帕沙）470 Vortioxetine（沃替西汀）473 附录1本书使用的期刊名称缩写表477 附录2专利文献代码481 附录3美国药品专利中的用途代码定义484 附录4美国药品市场独占权代码定义530 附录5美国FDA于2010—2014批准上市的药物名单563 英文索引607 中文索引611 CAS登记号索引613 下载方式现在，这份资料分享给大家。小编在公众号设置了自动回复功能，在公众号后台回复关键词：新药全合成 ●书籍分享||有机氧化反应原理与应用 ●书籍分享||有机卤化反应原理及应用 ●推荐合成书籍【有机缩合反应原理与应用】 ●推荐合成书籍【有机环合反应原理与应用】 ●书籍分享||有机还原反应原理与应用 ●ChemDraw使用让你从化学菜鸟变成老鸟 ●干货分享||有机合成: 策略与控制 ●干货分享||有机合成工艺研发-副反应抑制法 ●基础有机化学(邢其毅)第3、4版教材+习题解析 ●ChemDrawV20最新版详细安装图文教程 ●干货分享||核磁共振二维谱 ●书籍分享||全合成中的经典:更多的目标、战略和方法 ●书籍分享||实用药物化学 ●书籍分享||基于模仿创新的小分子药物发明 ●书籍分享||制药工艺开发-目前的化学与工程挑战 ●书籍分享||手性合成:不对称反应及其应用(第5版) ●书籍分享||新药研发案例研究--明星药物如何从实验室走向市场 ●书籍分享||英汉·汉英化学化工词汇 ●书籍分享||有机化学结构与功能（第四版） ●书籍分享||过渡金属有机化学(原著第6版） ●重磅书籍分享||不对称催化基础 ●书籍分享||药物设计学-唐赟

上市批准高管变更

2023-12-24

·药闻康策

从丙肝到乙肝，半部病毒性肝炎「消亡史」

☝ 点击上方一键预约 ☝ 最新最热的医药健康新闻政策轰轰烈烈的一部病毒性肝炎药物发展史，也是半部病毒性肝炎消亡史。2022年5月，第75届世界卫生大会通过了《2022-2030年全球卫生部门关于艾滋病、病毒性肝炎和性传播疾病行动计划》（简称《2022-2030行动计划》）决议[1]，对2016年大会通过的关于消除病毒性肝炎策略进行了修订，不仅提出了更具体的目标，更在国家层面给出了可量化指标。病毒性肝炎主要包括丙肝和乙肝，目前丙肝已经宣告90%以上的治愈率，乙肝的治愈率也随着诊疗方案的改进不断有新的突破，消除病毒性肝炎目标进入倒计时。我们试着从丙肝和乙肝疾病的“消除计划”，走进相关治疗药物的发展史。01一场事关全球的“行动计划”《2020-2030行动计划》提出的目标，仍然是到2030年消除病毒性肝炎的公共卫生威胁，即以2015年为基础，到2030年慢性乙型肝炎（CHB）和慢性丙型肝炎（CHC）新发感染率下降90%，死亡率降低65%，但今年提出了更具体的指标。乙肝目标：CHB新发病由2020年150万例(20/10万)，2025年降至85万例(11/10万)，2030年降至17万例(2/10万)；CHB死亡由2020年82万例(10/10万)，2025年降至53万例(7/10万)，2030年降至31万例(4/10万)。图1《2020-2030行动计划》对乙型肝炎发病率和死亡率的目标图片来源：《2022-2030年全球卫生部门关于艾滋病、病毒性肝炎和性传播疾病行动计划》丙肝目标：新发病由2020年157.5万例(20/10万)，2025年降至100万例(13/10万)，2030年降至35万例(5/10万)；CHC死亡由2020年29万例(5/10万)，2025年降至24万例(3/10万)，2030年降至14万例(2/10万)。图2《2020-2030行动计划》对丙型肝炎发病率和死亡率的目标图片来源：《2022-2030年全球卫生部门关于艾滋病、病毒性肝炎和性传播疾病行动计划》值得注意的是，关于《2020-2030行动计划》提出的七项关键措施指标，全球现有数据情况不容乐观。根据2020年发布的Polaris报告[2]，全球首针乙型肝炎疫苗接种率仅为49.1%；我国首针乙型肝炎疫苗接种率和3针乙肝疫苗覆盖率已超过全球数据，并已经达到WHO 2030年指标，但我国乙型肝炎诊断率为22%，治疗率仅为17%，距离WHO 2020年目标（30%/30%）都仍有很大距离。在丙型肝炎(丙肝)方面，形势同样严峻。Polaris的报告数据显示，虽然全球和我国的丙肝诊断率达到了2020年30%的目标，但全球丙肝治疗率仅为15%，我国只有10%，远未达到2020年30%的目标。因此，消除病毒性肝炎，任重而道远。图3《2020-2030行动计划》2025/2030年消除病毒性肝炎关键措施指标图片来源：《2022-2030年全球卫生部门关于艾滋病、病毒性肝炎和性传播疾病行动计划》02乙肝/丙肝患病率及患者人群特点乙肝一般指慢性乙型病毒性肝炎，指慢性乙肝病毒检测为阳性，病程超过半年或发病日期不明确而临床有慢性肝炎表现者。临床表现为乏力、畏食、恶心、腹胀、肝区疼痛等症状，严重可导致肝衰竭、肝硬化或肝癌。丙肝则一般分为急性和慢性。急性可出现恶心，食欲下降，全身无力，尿黄眼黄等表现。成人在不进行抗病毒干预的情况下，85%的患者发展为慢性丙型肝炎，儿童则有50%可自发性清除HCV。慢性丙型肝炎症状较轻，表现为容易疲劳，食欲欠佳，腹胀等，严重可导致肝硬化或肝癌。据WHO报道，2019年全球一般人群HBsAg流行率为3.8%，约有150万例新发HBV感染者，2.96亿例慢性HBV感染者（乙肝患者），82万例死于HBV感染所致的肝衰竭、肝硬化或HCC等相关疾病。根据Polaris国际流行病学合作组织推算，2016年我国一般人群HBsAg流行率为6.1%，慢性HBV感染者为8600万例。据WHO报道，2015年全球有慢性HCV感染者（丙肝患者）7100万例，39.9万例死于HCV感染引起的肝硬化或HCC。2019年全球有慢性HCV感染者5800万例，29万例死于HCV感染引起的肝硬化或HCC；2019年全球新发感染者约150万例。根据Polaris数据，2020年我国HCV感染者接近950万例[4]。“我大学毕业，面试的时候用人单位都说我是人才，一体检完就没信了。我尽力了，可是尽力有用吗？”这段感受出自吉利德科学公益支持的电影《不止不休》，改编自真实故事，以一名记者的成长史为切入口，折射出20年前乙肝患者和疾病、社会歧视作斗争的过程。目前虽然已经提倡全社会禁止歧视乙肝患者，但实际仍会受到不公正对待。03丙肝治疗药物发展历程丙肝病毒共存在6种基因型，丙肝患者以基因1型居多，约占70%。制药企业开发的口服抗病毒药物主要针对靶点为其非结构蛋白NS3、NS4A、NS5A和NS5B。最早上市的口服直接抗病毒药物（DAA）是NS3/4A蛋白酶抑制剂，包括波普瑞韦、特拉瑞韦、西美瑞韦。虽然NS3/4A蛋白酶抑制剂均需要与利巴韦林和干扰素注射联用，但由于将临床治愈率从40%提高到了80%以上，“干扰素注射+利巴韦林+DAA”还是成为丙肝的临床标准治疗方案而盛极一时。2013年12月6日，吉利德旗下索磷布韦以“突破性药物”的身份获得FDA批准上市，为基因2,3型丙肝患者提供了一种不需要注射干扰素的纯口服治疗方案，而且治愈率在90%以上。此后，丙肝治疗进入索磷布韦时代，大家也将其奉为丙肝神药。天价收购、超高治愈率、铺天盖地的媒体宣传让索磷布韦在上市之前就被医生和患者熟知，即便是吉利德定了1000美元/片（84000美元/疗程）的高昂定价，也无法阻挡临床处方的热情。2014年，索磷布韦上市的第一年，销售收入102.83亿美元，创下新药上市第一年销售收入记录。2014年，吉利德旗下Harvoni（索磷布韦/雷迪帕韦）美国上市，为患者数量最多的基因1型丙肝患者提供了纯口服治疗方案，而且治疗周期更短，治愈率更高。Harvoni获批上市2个多月便贡献21.27亿美元收入。同年，艾伯维的四合一丙肝新药Viekira Park（达塞布韦钠/奥比他韦/帕利瑞韦/利托那韦）获得FDA批准，之后不久又获得欧盟批准，因为同样是纯口服方案，治愈率也不相上下，吉利德迎来了竞争对手，医保支付方也终于有了和吉利德讨价还价的筹码。但如今看来，这款药没有逃脱撤市的命运。2015年是吉利德把丙肝药业务做得最大的年份，也是暗藏危机的一年。索磷布韦销售额腰斩，纵然Harvoni全年销售成绩艳丽，但从季度销售收入上看，已经不再增长，毕竟全球的医疗卫生支出承受能力不可能无限放大。2016年，默沙东的丙肝新药Zepatier（艾尔巴韦/格拉瑞韦）终于获得FDA批准上市，口服丙肝药时代最后一个巨头进场。默沙东出招凌厉，虽然时间上已经不占优势，但是会打价格战。同年，吉利德覆盖全基因型的丙肝产品Epclusa（索磷布韦/维帕他韦）美国上市，产品性能继续优化的空间已不大，加上丙肝患者日益减少，降价似乎成了最有效的出路。受患者减少和降价影响，2016年全球丙肝市场规模大约190亿美元，较2015年下降了30%以上。2017年，吉利德和艾伯维分别推出全基因型丙肝药物Vosevi（索磷布韦/维帕他韦/伏西瑞韦）和Maviret（格卡瑞韦/哌仑他韦）。此后，吉利德更是表态不再投入资源开发丙肝新药。至此，一个拥有庞大患者人群及及市场的疾病逐步走向消亡，关于丙肝药的头号玩家竞争也基本步入终局。此后，国产丙肝药，如歌礼制药旗下达诺瑞韦和拉维达韦，凯因科技旗下可洛派韦，东阳光药业旗下依米他韦也相继上市。如今，丙通沙Epclusa一个疗程国内只需自付不到2000元，相比医保前一个疗程近7万的价格降低了97%，丙肝患者是最大的受益者。九部委联合发布的《消除丙型肝炎公共卫生危害行动工作方案（2021—2030年）》提出“我国丙肝患者抗病毒治疗的临床治愈率超过95%、慢性丙肝抗病毒治疗率超过80%”的目标，这与我国目前的实际情况仍有很大差距。显然，未来几年，是多家丙肝药企业迫切需要抢占的时间窗口。04乙肝治疗药物发展历程1990年，干扰素-α的发现，使得人们开启了乙肝治疗的新篇章。因为这个药物具有稳定可靠的抗病毒效果，能通过调节机体免疫力，使得被乙肝病毒感染的肝细胞得以免疫系统识别并消灭，从而起到治疗乙肝的作用。不过，干扰素-α属于短效干扰素，不够稳定、代谢快、需要每天都给药，比较麻烦，副作用较大，效果也不是很理想。到了1998年，葛兰素史克研发出了第一款口服抗病毒药物—拉米夫定，它是一种核苷类似物，对乙肝病毒具有良好的抑制效果，但同时也出现了耐药问题。为了克服这个问题，该公司又研发的一款核苷药—阿德福韦酯，它能在一定程度上克服拉米夫定的耐药问题，但它的肾毒性较大，同样无法满足广大乙肝患者的需求。2005年，百时美施贵宝旗下核苷药恩替卡韦美国上市，其效果优于拉米夫定，且耐药率低，一经上市就受到追捧。直到现在，恩替卡韦依旧是治疗慢乙肝的一线治疗药物。虽然恩替卡韦对初治患者效果好，耐药率低，但对使用了拉米夫定且耐药的患者，却相对更容易耐药。2008年，吉利德旗下核苷药替诺福韦酯获FDA批准用于乙肝（最早2001年上市用于艾滋病）。后来又出现了吉利德的丙酚替诺福韦（TAF，别名富马酸丙酚替诺福韦、富马酸磷丙替诺福韦）、豪森的艾米替诺福韦（TMF，别名艾美酚胺替诺福韦片），都是替诺福韦酯的升级版。这两款药能进入肝细胞胞浆并对肝内病毒复制起效，安全性更高且抗病毒效果更好。核苷药物的出现，给慢乙肝患者带来了极大的希望，降低了肝硬化、肝癌的发生风险。但可惜的是，无论哪种核苷药物，都难以治愈乙肝，只能抑制病毒复制，减少或延缓病情的进展，且需要长期服药。随着科学技术的进步，人们对干扰素α进行了“升级”，由此诞生了聚乙二醇干扰素α，也就是长效干扰素，它的持续时间更长，效果也更好。随后，聚乙二醇干扰素α-2b上市。2010年左右，当时医学界已经有人发现，经过核苷和聚乙二醇干扰素α联合治疗的患者，会出现HBsAg的清除。后续研究表明，核苷经治优势患者加用聚乙二醇干扰素临床治愈率可达30%-80%。借助这一发现，2015-2016年，我国《慢乙肝防治指南》首次提出临床治愈的理念。2017-2018年，临床治愈在国内外达成共识，理念获得国际认可。中国慢乙肝临床治愈（珠峰）工程项目启动。2020年，《慢乙肝临床治愈（功能性治愈）专家共识》的发布，明确了聚乙二醇干扰素α在实现慢乙肝患者临床治愈中的地位。2022年，《慢乙肝防治指南》2022版的发布，再次确定了聚乙二醇干扰素α在实现慢乙肝患者临床治愈中的重大意义。虽然慢性乙肝尚无法治愈，但彻底清除乙肝病毒，实现乙肝病毒学治愈指日可待。2021年初，吉利德宣布与VirBiotechnology达成一项临床合作，旨在评估和开发功能性治愈慢性乙肝的新型联合治疗策略。今年年初，歌礼制药宣布其皮下注射PD-L1抗体ASC22（恩沃利抗体）可以实现慢性乙型肝炎功能性治愈的消息也引起广泛关注。此外，腾盛博药旗下BRII-835、GSK与Ionis联合开发的bepirovirsen也备受瞩目。鉴于丙肝的“消亡史”，我们有理由相信未来乙肝也可能被治愈。05结语期待乙肝、丙肝、丁肝等病毒性肝炎彻底被消除的那一天，人类用智慧和科学攻克并战胜包括病毒性肝炎在内的所有疾病。这是信念，也是使命。(来源:药智网)药闻康策新媒体矩阵微信公众号点击下方一键关注【免责声明】1.“药闻康策”部分文章信息来源于网络转载是出于传递更多信息之目的，并不意味着赞同其观点或证实其内容的真实性。如对内容有疑议，请及时与我司联系。2.“药闻康策”致力于提供合理、准确、完整的资讯信息，但不保证信息的合理性、准确性和完整性，且不对因信息的不合理、不准确或遗漏导致的任何损失或损害承担责任。3.“药闻康策”所有信息仅供参考，不做任何商业交易或医疗服务的根据，如自行使用“药闻康策”内容发生偏差，我司不承担任何责任，包括但不限于法律责任，赔偿责任。欢迎转发分享、点赞、点在看

疫苗临床研究放射疗法

2023-12-12

·SYNAPSE

What are NS5A inhibitors and how do you quickly get the latest development progress?

NS5A is a crucial protein found in the human body that plays a significant role in the life cycle of the hepatitis C virus (HCV). It is involved in viral replication, assembly, and release, making it an attractive target for antiviral therapies. NS5A interacts with various host proteins and cellular pathways, modulating the immune response and promoting viral persistence. Inhibiting NS5A can disrupt HCV replication, leading to reduced viral load and improved clinical outcomes. Understanding the function of NS5A is essential for developing effective treatments against HCV and combating the global burden of this infectious disease. The analysis of the current competitive landscape of target NS5A reveals that Gilead Sciences, Inc., AbbVie, Inc., and Merck & Co., Inc. are the leading companies in terms of R&D progress. These companies have drugs in multiple phases of development, including the approved phase. The indication analysis shows that drugs under the target NS5A have been approved for various indications related to Hepatitis C, Fibrosis, Cirrhosis, and other diseases. The drug types progressing most rapidly are small molecule drugs and synthetic peptides, indicating intense competition in the market. China is a significant player in the development of drugs targeting NS5A, with the highest number of drugs in the approved phase. Other countries such as Japan, European Union, and the United States also have a considerable presence in the development of NS5A drugs. The future development of target NS5A is promising, with ongoing research and development by various companies and institutions. The competition in the market is expected to intensify, especially for small molecule drugs and synthetic peptides. Further advancements in the treatment of Hepatitis C and other related indications can be expected with the continued efforts of the pharmaceutical industry. How do they work?NS5A inhibitors are a type of antiviral medication that target the NS5A protein in the hepatitis C virus (HCV). From a biomedical perspective, these inhibitors work by blocking the function of the NS5A protein, which is essential for viral replication and assembly. By inhibiting NS5A, these drugs help to prevent the spread and multiplication of the hepatitis C virus in the body. NS5A inhibitors are commonly used in combination with other direct-acting antiviral drugs to treat chronic hepatitis C infection. They have shown high efficacy in achieving sustained virologic response (SVR), which means that the virus is undetectable in the blood six months after completing treatment. These inhibitors have revolutionized the treatment of hepatitis C, offering shorter treatment durations, improved tolerability, and higher cure rates compared to older therapies. It's important to note that NS5A inhibitors are specific to the treatment of hepatitis C and are not used for other viral infections or diseases. They are typically prescribed by healthcare professionals and should be taken as directed to ensure optimal treatment outcomes. Common examples of NS5A inhibitors include ledipasvir, daclatasvir, and ombitasvir. List of NS5A InhibitorsThe currently marketed NS5A inhibitors include: Emitasvir PhosphateRavidasvir HydrochlorideCoblopasvir hydrochlorideGlecaprevir/PibrentasvirGlecaprevir/PibrentasvirElbasvirSofosbuvir/VelpatasvirElbasvir/GrazoprevirOmbitasvir/Paritaprevir/RitonavirLedipasvir/SofosbuvirFor more information, please click on the image below. What are NS5A inhibitors used for?NS5A inhibitors are commonly used in combination with other direct-acting antiviral drugs to treat chronic hepatitis C infection. For more information, please click on the image below to log in and search. How to obtain the latest development progress of NS5A inhibitors?In the Synapse database, you can keep abreast of the latest research and development advances of NS5A inhibitors anywhere and anytime, daily or weekly, through the "Set Alert" function. Click on the image below to embark on a brand new journey of drug discovery!

100 项与奥比他韦相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D10576	奥比他韦	-	DB09296

研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
慢性丙型肝炎基因型 1b	临床2期	-	AbbVie, Inc.	2012-08-01
慢性丙型肝炎基因型 3	临床2期	-	AbbVie, Inc.	2011-09-01
慢性丙型肝炎基因型 1	临床2期	美国	AbbVie, Inc.	2011-03-01
慢性丙型肝炎基因型 1	临床2期	波多黎各	AbbVie, Inc.	2011-03-01

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临床结果

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分期

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT02486406 (ZIRCON, Pubmed \| Adv Ther) 人工标引	临床2/3期	丙型肝炎	26	OBV+ PTV+ritonavir+ DSV+DSV+ribavirin	簾構鹽艱膚淵觸蓋蓋鹹(餘獵積構網鑰鏇淵醖觸) = 廠顧繭糧襯壓鹹窪鑰憲醖糧製餘鑰憲夢廠窪選 (構艱衊簾顧艱願遞獵醖, 81.1 ~ 99.3) 更多	积极	2020-07-01
P1384 (ERA2020)	N/A	肾功能不全 \| 慢性丙型肝炎 hemoglobin \| serum creatinine	235	Direct Acting Anti-Virus (Anemic CKD patients)	積構鏇壓繭淵鏇範觸鹽(鬱範鹹鹽積範遞構夢糧) = 衊鏇膚範願繭廠鑰願繭襯構獵醖餘蓋廠積願襯 (醖淵蓋築願鏇廠衊鹽構 ) 更多	积极	2020-06-06
P1384 (ERA2020)	N/A	肾功能不全 \| 慢性丙型肝炎 hemoglobin \| serum creatinine	235	Direct Acting Anti-Virus (Non-anemic CKD patients)	積構鏇壓繭淵鏇範觸鹽(鬱範鹹鹽積範遞構夢糧) = 範醖膚製觸範淵襯積衊襯構獵醖餘蓋廠積願襯 (醖淵蓋築願鏇廠衊鹽構 ) 更多	积极	2020-06-06
SP138 (ERA2019)	N/A	终末期肾脏病 \| 慢性丙型肝炎	53	Ombitasvir 50 mg / Paritaprevir 150 mg / Ritonavir 100 mg	觸獵鬱製顧積夢遞糧觸(醖網鑰網鏇觸壓製憲蓋) = Anemia was observed during in 7 patients (13.2%), which required transfusion, erythropoietin therapy, and modification of RBV dose to be every other day 遞衊艱繭憲窪膚積艱選 (鹽鬱糧積糧夢憲鏇鹹襯 )	积极	2019-06-13
NCT01609933 (Pubmed)	临床2期	慢性丙型肝炎基因型 1	32	Ombitasvir, paritaprevir, and ritonavir	鏇淵顧築衊醖網膚遞襯(憲鏇鏇構壓壓遞遞壓糧) = 鬱壓醖製範鹹鑰醖鹹艱夢顧夢願蓋選艱顧醖網 (夢淵淵鏇鹽窪艱淵網壓 )	积极	2019-01-01
UEGW2018	N/A	肝硬化 increased total bilirubin \| prolonged INR	5,853	Ombitasvir, Paritaprevir/ r+Dasabuvir+Ribavirin	鑰襯獵獵蓋淵獵襯衊遞(糧鹹糧壓顧鹽繭齋網獵) = 4 觸衊獵鏇壓齋鑰襯範鏇 (鬱獵鏇鏇築鹹蓋鹽膚遞 ) 更多	积极	2018-10-01
UEGW2018	N/A	HCV	22	DAA- resection+ RFA	鑰願積觸獵鑰醖網蓋廠(繭膚鏇構選鹽淵鹹鑰鏇) = Two female patients died of acute liver insufficiency (9.5%) one after completing 12 weeks of treatment, and the other in week 7 of DAA therapy (in the DAA- resection+ RFA group) 艱淵膚淵繭製醖選選襯 (蓋鹹顧鏇鹽鬱鬱獵廠餘 ) 更多	积极	2018-10-01
UEGW2018	N/A	HCV	22	Control- resection+ RFA		积极	2018-10-01
UEGW2016	N/A	代偿期肝硬化	-	Ombitasvir / Paritaprevir / Ritonavir + Dasabuvir + Ribavirin	選構願鏇齋齋壓糧繭鏇(網憲觸淵選選蓋網鏇鏇) = 2% 構齋築鑰鏇齋蓋廠鹹醖 (鏇鹹積鹹構簾簾窪廠憲 ) 更多	-	2016-10-01
NCT01458535 (Navigator, CTgov)	临床2期	慢性丙型肝炎基因型 3	61	ABT-450+ribavirin+ritonavir+ABT-267 (ABT-450/r and ABT-267 Plus RBV in Genotype 1 Participants)	衊壓廠獵獵構醖壓積築 = 積構鹹鑰膚觸獵鹽鹹觸廠窪獵遞窪膚範憲壓憲 (繭鬱鬱齋積襯願蓋醖製, 膚選鑰鏇築網顧壓廠廠 ~ 鹽顧顧齋窪衊構餘窪蓋) 更多	-	2016-07-11
NCT01458535 (Navigator, CTgov)	临床2期	慢性丙型肝炎基因型 3	61	ABT-450+ribavirin+ritonavir+ABT-267 (ABT-450/r and ABT-267 Plus RBV in Genotype 2 Participants)	衊壓廠獵獵構醖壓積築 = 窪蓋窪鹹膚餘願顧膚鏇廠窪獵遞窪膚範憲壓憲 (繭鬱鬱齋積襯願蓋醖製, 遞窪願繭繭簾簾願願繭 ~ 觸鹹壓築襯蓋衊製艱淵) 更多	-	2016-07-11
NCT01685203 (Pubmed \| Gastroenterology)	临床2期	慢性丙型肝炎基因型 1b	-	Ombitasvir (25 mg), Paritaprevir (150 mg), and Ritonavir (100 mg)	鏇鏇鹽糧憲積鬱壓淵廠(構艱鬱餘膚壓獵淵觸蓋) = 製顧壓淵糧積蓋窪憲糧壓顧遞夢鏇夢鏇鹽膚鬱 (蓋築糧網窪簾艱遞艱構 )	-	2015-10-01
PEARL-II \| PEARL-III \| TURQUOISE-II (UEGW2015)	临床3期	慢性丙型肝炎基因型 1b IL28B non-CC genotype \| baseline viral loads â¥800,000 IU/mL	369	Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir	鏇衊範構繭鹹築衊鬱齋(衊鹽製顧網顧鏇鏇簾鹹) = 0.3% 衊憲鹽積繭襯憲鹹齋簾 (夢鹹襯選淵鏇淵鑰糧遞 ) 更多	积极	2015-10-01