Daclatasvir dihydrochloride/Asunaprevir/Beclabuvir hydrochloride(Daclatasvir dihydrochloride/Asunaprevir/Beclabuvir hydrochloride) - 药物靶点：NS3 x NS5A x NS5B polymerase_在研适应症：纤维化，丙型肝炎_专利_临床

概要

基本信息

药物类型

小分子化药

别名

Asunaprevir/beclabuvir/daclatasvir、Asunaprevir/daclatasvir/BMS 791325、BMS 791325/asunaprevir/daclatasvir

+ [5]

靶点

NS3 x NS5A x NS5B polymerase

作用机制

NS3抑制剂(丙型肝炎病毒非结构蛋白3抑制剂)、NS5A抑制剂(非结构蛋白5A抑制剂)、NS5B polymerase抑制剂(丙型肝炎病毒NS5B RNA依赖的RNA聚合酶抑制剂)

治疗领域

感染消化系统疾病其他疾病

在研适应症

纤维化丙型肝炎

非在研适应症-

原研机构

Bristol Myers Squibb Co.

在研机构

Bristol Myers Squibb Co.

非在研机构-

最高研发阶段批准上市

首次获批日期

日本 (2016-12-19),

纤维化丙型肝炎

最高研发阶段(中国)无进展

特殊审评特殊审批 (中国)

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结构

分子式C36H46ClN5O5S

InChIKeyIHXVACFNNPBRLK-VTFHPOPBSA-N

CAS号958002-36-3

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关联

15

项与 Daclatasvir dihydrochloride/Asunaprevir/Beclabuvir hydrochloride 相关的临床试验

NCT02292966 / Withdrawn临床4期IIT

Impact of HCV Eradication on Neurocognitive Functions and CNS Metabolism: a Trial of Daclatasvir, Asunaprevir and Beclabuvir for Patients With HCV Genotype 1 Infection

The purpose of this study is to examine whether neurocognitive impairments experienced by patients with chronic hepatitis C virus (HCV) infection can be reversed by treating HCV, with a new combination of direct acting antiviral drugs (daclatasvir (DCV), asunaprevir (ASV) and beclabuvir (BCV)). The study will assess the effect of HCV on the central nervous system (CNS) by assessing neurocognitive function and brain injury prior to treatment, and comparing it to the end of treatment, and 4, 12 and 24 weeks after treatment.

开始日期2015-07-01

申办/合作机构

Kirby Institute

[+1]

NCT02309450 / Withdrawn临床2期IIT

Pilot Study to Assess Efficacy and Safety of a Triple Therapy With Asunaprevir, Daclatasvir and BMS-791325 in HCV Genotype 4-infected Patients After Failure of Pegylated Interferon-Ribavirin Regimen

ANRS HC 33 is a pilot study to assess efficacy and safety of a DCV 3DAA therapy with Asunaprevir, Daclatasvir and BMS-791325 in HCV genotype 4-infected patients after failure of pegylated Interferon-Ribavirin regimen.
Proportion of patients with cirrhosis will be limited to 50% of all patients included, cirrhosis being defined as a METAVIR score of F4 on the liver biopsy or an hepatic impulse elastometry ≥ 14 kPa or a Fibrotest® result > 0,75.

开始日期2014-12-01

申办/合作机构

ANRS, Emerging Infectious Diseases

[+1]

NCT02175966 / Completed临床2期

Short Duration Combination Therapy With Daclatasvir, Asunaprevir, BMS-791325 and Sofosbuvir in Subjects Infected With Chronic Hepatitis C (FOURward Study)

The purpose of the study is to determine whether the combination of Daclatasvir (DCV), Asunaprevir (ASV), BMS-791325 and Sofosbuvir is effective and safe in treating Hepatitis-C virus.

开始日期2014-07-28

申办/合作机构

Bristol Myers Squibb Co.

100 项与 Daclatasvir dihydrochloride/Asunaprevir/Beclabuvir hydrochloride 相关的临床结果

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100 项与 Daclatasvir dihydrochloride/Asunaprevir/Beclabuvir hydrochloride 相关的转化医学

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100 项与 Daclatasvir dihydrochloride/Asunaprevir/Beclabuvir hydrochloride 相关的专利（医药）

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8

项与 Daclatasvir dihydrochloride/Asunaprevir/Beclabuvir hydrochloride 相关的文献（医药）

2018-09-01·Journal of Gastroenterology1区 · 医学

Potent viral suppression and improvements in alpha-fetoprotein and measures of fibrosis in Japanese patients receiving a daclatasvir/asunaprevir/beclabuvir fixed-dose combination for the treatment of HCV genotype-1 infection

1区 · 医学

Article

作者: Chayama, Kazuaki ; Toyota, Joji ; Ikeda, Fusao ; McPhee, Fiona ; Tanaka, Katsuaki ; Ido, Akio ; Noviello, Stephanie ; Kumada, Hiromitsu ; Inada, Yukiko ; Tomita, Eiichi ; Karino, Yoshiyasu ; Takaguchi, Koichi ; Naganuma, Atsushi ; Fujiyama, Shigetoshi ; Yoshiji, Hitoshi ; Ishikawa, Hiroki ; Akuta, Norio ; Watanabe, Hideaki

BACKGROUNDIn the UNITY-3 study, 96% sustained virologic response (SVR12) rate was observed in Japanese patients with hepatitis C virus (HCV) genotype (GT)-1 infection treated for 12 weeks with fixed-dose daclatasvir, asunaprevir, and beclabuvir (DCV-TRIO). As HCV clearance may improve liver outcomes, we assessed hepatic fibrosis and alpha-fetoprotein (AFP), a hepatocellular carcinoma risk marker, pre- and post-treatment in UNITY-3.METHODSTreatment-naive or interferon-experienced UNITY-3 patients with HCV GT-1 who received twice-daily DCV-TRIO were assessed for fibrosis [FibroTest; FibroScan; fibrosis-4 index (FIB-4), aspartate-aminotransferase-to-platelet-ratio index] and AFP at baseline and Weeks 4 (FIB-4 only), 12 or 24 post-treatment.RESULTSOf 217 patients, 99% had GT-1b infection, 46% were aged > 65 years, 21% had compensated cirrhosis, and 26% baseline HCV-RNA > 10⁷ IU/mL. All GT-1b patients treated ≥ 4 weeks achieved SVR12 with (n = 54) or without (n = 144) baseline NS5A polymorphisms associated with DCV resistance (positions 28/30/31/93). Statistically significant post-treatment reductions from baseline were observed for all fibrosis measures and AFP, with numerically greater reductions in cirrhotic patients. FibroTest category improved in 44%, remained stable in 50%, and worsened in 6% of patients; 98% with baseline AFP < 6 μg/L remained < 6 μg/L and 51% with baseline AFP ≥ 6 μg/L were < 6 μg/L post-treatment.CONCLUSIONSDCV-TRIO administered for 12 weeks to Japanese patients with primarily GT-1b infection achieved a high SVR12 rate and resulted in improved measures of hepatic fibrosis and serum AFP that may reduce the risk of future liver disease progression and hepatocellular carcinoma, particularly in those with compensated cirrhosis.

2018-06-03·Expert Opinion on Drug Metabolism & Toxicology2区 · 医学

Pharmacokinetic and pharmacodynamic evaluation of daclatasvir, asunaprevir plus beclabuvir as a fixed-dose co-formulation for the treatment of hepatitis C

2区 · 医学

Review

作者: Esposito, Isabella ; Trinks, Julieta ; Marciano, Sebastián

INTRODUCTIONMany reports have evaluated the clinical efficacy and safety of the fixed-dose all-oral combination of daclatasvir, asunaprevir, and beclabuvir (DCV-TRIO), which was approved in Japan in December 2016 for the treatment of hepatitis C genotype (GT)-1 infection. Areas covered: This article reviews the pharmacodynamic and pharmacokinetic properties of the DCV-TRIO combination. The topics covered include data regarding the drug's absorption, distribution, metabolism, excretion, and antiviral activity strategies. Its therapeutic efficacy and safety in GT-1 infection from phase 2/3 clinical trials are also discussed. Expert opinion: The ideal regimen for the treatment of Hepatitis C virus infection should be potent, pangenotypic, Ribavirin-free, safe, co-formulated, and affordable. Considering these characteristics, DCV-TRIO is neither pangenotypic nor potent enough against GT-1a, regardless of the presence or absence of cirrhosis. Other potential limitations of this regimen are its dosification (twice-daily), and the fact that since it includes a protease inhibitor, it is contraindicated in decompensated cirrhosis. For these reasons, it has only been approved in Japan, where more than 70% of the patients are infected with GT-1b. However, this co-formulation might still have a place in the treatment of non-cirrhotic patients infected with GT-1b provided that massive access to treatment is facilitated.

2017-12-01·Journal of Gastroenterology and Hepatology

Daclatasvir/asunaprevir/beclabuvir, all‐oral, fixed‐dose combination for patients with chronic hepatitis C virus genotype 1

Article

作者: Lim, Young Suk ; Isakov, Vasily ; Treitel, Michelle ; Hu, Wenhua ; Hu, Tsung‐Hui ; Lee, Youn‐Jae ; Ahn, Sang Hoon ; Yoon, Ki Tae ; Heo, Jeong ; Paik, Seung Woon ; Scott Swenson, Eugene ; Kao, Jia‐Horng ; Peng, Cheng‐Yuan ; Chu, Chi‐Jen ; Yin, Philip D ; Yu, Ming‐Lung ; McPhee, Fiona ; Chang, Ting‐Tsung

AbstractBackground and AimThis multinational (Taiwan, South Korea, Russia) phase 3 study evaluated the all‐oral, ribavirin‐free, fixed‐dose combination (DCV‐TRIO) of daclatasvir (NS5A inhibitor) 30 mg, asunaprevir (NS3 inhibitor) 200 mg, and beclabuvir (NS5B inhibitor) 75 mg, in patients with chronic hepatitis C virus genotype‐1 infection, with or without compensated cirrhosis.MethodsUNITY‐4 (NCT02170727) was an open‐label, two‐cohort study in which 169 patients, treatment‐naive (n = 138) or treatment‐experienced (n = 31), received twice‐daily DCV‐TRIO for 12 weeks with 24 weeks of post‐treatment follow‐up. The primary efficacy end point was sustained virologic response at post‐treatment week 12 (SVR12) in treatment‐naive patients.ResultsEighty‐eight (52%) patients were men, 81 (48%) Taiwanese, 78 (46%) Korean, and 10 (6%) Russian; 23 (14%) had compensated cirrhosis, and 52 (31%) were IL28B (rs1297860) non‐CC genotype. Baseline resistance‐associated NS5A polymorphisms (L31 and/or Y93) were detected in 25/165 (15%) patients with available genotype‐1 sequencing data. SVR12 was achieved by 98.6% (136/138; 95% confidence interval: 94.9–99.8%) of treatment‐naive and 100% (31/31; 95% confidence interval: 88.8–100%) of treatment‐experienced patients. Both virologic failures were found to be infected with hepatitis C virus genotype‐6g; 100% SVR12 was observed for genotype‐1a (n = 8) and genotype‐1b (n = 157). Two patients experienced serious adverse events. Eight (5%) patients experienced reversible grade 3/4 alanine aminotransferase or aspartate aminotransferase elevations, leading to discontinuation in four (2%); all achieved SVR12. There were no grade 3/4 total bilirubin increases and no deaths.ConclusionsTwelve weeks of DCV‐TRIO was well tolerated and provided 100% SVR12 in treatment‐naive and treatment‐experienced patients with genotype‐1 infection, with or without cirrhosis, including those with baseline NS5A‐L31 or NS5A‐Y93 resistance‐associated substitutions.

100 项与 Daclatasvir dihydrochloride/Asunaprevir/Beclabuvir hydrochloride 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	J05AP58	-

研发状态

批准上市

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适应症	国家/地区	公司	日期
纤维化	日本	Bristol Myers Squibb Co.	2016-12-19
丙型肝炎	日本	Bristol Myers Squibb Co.	2016-12-19

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适应症	最高研发状态	国家/地区	公司	日期
丙型肝炎	药物发现	澳大利亚	Bristol Myers Squibb Co.	2013-12-06

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临床结果

适应症

分期

评价

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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


NCT02175966 (FOURward, CTgov)	临床2期	慢性丙型肝炎	35	DCV 3DAA+SOF (4 Weeks DCV 3DAA + SOF)	網淵廠願簾顧鹹鏇積鏇(獵鹹鹽醖鹹壓繭糧夢艱) = 餘範構餘顧餘壓醖鹹網齋餘積蓋製壓廠遞鹹艱 (淵簾網夢醖製醖膚夢築, 築遞願壓積淵範衊蓋鏇 ~ 窪艱鏇鏇夢衊鬱憲範範) 更多	-	2019-05-29
				DCV 3DAA+SOF (6 Weeks DCV 3DAA + SOF)	網淵廠願簾顧鹹鏇積鏇(獵鹹鹽醖鹹壓繭糧夢艱) = 願夢築夢糧衊壓積簾夢齋餘積蓋製壓廠遞鹹艱 (淵簾網夢醖製醖膚夢築, 衊獵鹽鬱蓋衊鏇艱襯艱 ~ 範鹽製憲遞餘觸鑰積壓) 更多
NCT02170727 (UNITY-4, Pubmed) 人工标引	临床3期	慢性丙型肝炎基因型 1	169	Daclatasvir/asunaprevir/beclabuvir (treatment-naive patients)	(蓋糧鏇製夢願餘觸構淵) = 遞鬱襯遞齋夢簾築簾壓築顧鏇鬱憲鹽網簾齋夢 (鑰網製繭鹹獵鹽糧蓋窪, 94.9 ~ 99.8)	积极	2017-12-01
				Daclatasvir/asunaprevir/beclabuvir (treatment-experienced patients)	(蓋糧鏇製夢願餘觸構淵) = 網願膚餘鏇築鏇鹽網鹽築顧鏇鬱憲鹽網簾齋夢 (鑰網製繭鹹獵鹽糧蓋窪, 88.8 ~ 100)
UEGW	N/A	慢性丙型肝炎基因型 1	-	Daclatasvir, Asunaprevir, Beclabuvir	簾襯積艱鬱齋構鏇醖鬱(遞餘蓋衊繭觸鹽構獵鹽) = 14.3% (95%CI [12.0–16.9]) 鹽鹽鏇簾鏇醖鹽壓鹹觸 (積淵鏇鹽鹹鬱夢糧築遞 ) 更多	-	2017-10-01
				Ribavirin