Delving into the Latest Updates on Daclatasvir dihydrochloride/Asunaprevir/Beclabuvir hydrochloride with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Asunaprevir/beclabuvir/daclatasvir, Asunaprevir/daclatasvir/BMS 791325, BMS 791325/asunaprevir/daclatasvir

+ [5]

Target

NS3 x NS5A x NS5B polymerase

Mechanism

NS3 inhibitors(Hepatitis C virus (HCV) nonstructural protein 3 inhibitors), NS5A inhibitors(Nonstructural protein 5A inhibitors), NS5B polymerase inhibitors(Hepatitis C virus NS5B RNA-dependent RNA polymerase inhibitors)

Therapeutic Areas

Infectious DiseasesDigestive System DisordersOther Diseases

Active Indication

FibrosisHepatitis C

Inactive Indication-

Originator Organization

Bristol Myers Squibb Co.

Active Organization

Bristol Myers Squibb Co.

Inactive Organization-

Drug Highest PhaseApproved

First Approval Date

JP (19 Dec 2016),

FibrosisHepatitis C

RegulationSpecial Review Project (CN)

Login to view timeline

Structure

Molecular FormulaC36H46ClN5O5S

InChIKeyIHXVACFNNPBRLK-VTFHPOPBSA-N

CAS Registry958002-36-3

View All Structures (3)

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.

Start Date01 Jul 2015

Sponsor / Collaborator

Kirby Institute

[+1]

NCT02309450 / WithdrawnPhase 2IIT

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.

Start Date01 Dec 2014

Sponsor / Collaborator

ANRS, Emerging Infectious Diseases

[+1]

NCT02175966 / CompletedPhase 2

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.

Start Date28 Jul 2014

Sponsor / Collaborator

Bristol Myers Squibb Co.

100 Clinical Results associated with Daclatasvir dihydrochloride/Asunaprevir/Beclabuvir hydrochloride

Login to view more data

100 Translational Medicine associated with Daclatasvir dihydrochloride/Asunaprevir/Beclabuvir hydrochloride

Login to view more data

100 Patents (Medical) associated with Daclatasvir dihydrochloride/Asunaprevir/Beclabuvir hydrochloride

Login to view more data

8

Literatures (Medical) associated with Daclatasvir dihydrochloride/Asunaprevir/Beclabuvir hydrochloride

01 Sep 2018·Journal of GastroenterologyQ1 · MEDICINE

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

Q1 · MEDICINE

Article

Author: 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.

03 Jun 2018·Expert Opinion on Drug Metabolism & ToxicologyQ2 · MEDICINE

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

Q2 · MEDICINE

Review

Author: 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.

01 Dec 2017·Journal of Gastroenterology and Hepatology

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

Article

Author: 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 Deals associated with Daclatasvir dihydrochloride/Asunaprevir/Beclabuvir hydrochloride

Login to view more data

External Link

KEGG	Wiki	ATC	Drug Bank
-	-	J05AP58	-

R&D Status

Approved

10 top approved records.

Login

to view more data

Indication	Country/Location	Organization	Date
Fibrosis	JP	Bristol Myers Squibb Co.	19 Dec 2016
Hepatitis C	JP	Bristol Myers Squibb Co.	19 Dec 2016

Developing

10 top R&D records.

Login

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Hepatitis C	Discovery	AU	Bristol Myers Squibb Co.	06 Dec 2013

Login to view more data

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02175966 (FOURward, CTgov)	Phase 2	Hepatitis C, Chronic	35	DCV 3DAA+SOF (4 Weeks DCV 3DAA + SOF)	zbwgipgnca(njgbrsruae) = vrdthqaykx alqbbrnatn (fnjdfadjnu, cmdrdlgsoc - qihmotdptc) View more	-	29 May 2019
				DCV 3DAA+SOF (6 Weeks DCV 3DAA + SOF)	zbwgipgnca(njgbrsruae) = qxcqevazzs alqbbrnatn (fnjdfadjnu, kheflieyui - qwbsxbtoyz) View more
NCT02170727 (UNITY-4, Pubmed) Manual	Phase 3	Chronic hepatitis C genotype 1	169	Daclatasvir/asunaprevir/beclabuvir (treatment-naive patients)	(ylzzdrozva) = fyfmahpruv wxtayqsabc (lwpodwjtkm, 94.9 - 99.8)	Positive	01 Dec 2017
				Daclatasvir/asunaprevir/beclabuvir (treatment-experienced patients)	(ylzzdrozva) = bixxqamwdo wxtayqsabc (lwpodwjtkm, 88.8 - 100)
UEGW	Not Applicable	Chronic hepatitis C genotype 1	-	Daclatasvir, Asunaprevir, Beclabuvir	crlikdntrc(tjsjgaglqv) = 14.3% (95%CI [12.0–16.9]) efnthzegza (oyjuhqatgq ) View more	-	01 Oct 2017
				Ribavirin