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

Action

inhibitors

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

Chronic hepatitis C genotype 1Kidney Failure, Chronic

Originator Organization

Bristol Myers Squibb Co.

Active Organization

Bristol Myers Squibb Co.

Inactive Organization-

Drug Highest PhaseApproved

First Approval Date

Japan (19 Dec 2016),

FibrosisHepatitis C

RegulationSpecial Review Project (China)

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Structure/Sequence

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

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

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

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8

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

11 Feb 2020·Expert Opinion on Pharmacotherapy

Efficacy and safety of a fixed dose combination tablet of asunaprevir + beclabuvir + daclatasvir for the treatment of Hepatitis C

Review

Author: Buonomo, Antonio Riccardo ; Gentile, Ivan ; Scotto, Riccardo ; Pinchera, Biagio ; Zappulo, Emanuela ; Maraolo, Alberto Enrico

Introduction: Hepatitis C virus (HCV) is estimated to infect approximately 70 million people worldwide. If left untreated, chronic infection can progress to cirrhosis, liver failure or hepatocellular carcinoma. The advent of new direct-acting antivirals (DAA) has revolutionized patients' chances of treatment and viral elimination. Currently, several DAA options are available on the market.Areas covered: This review focuses on the pharmacokinetics, efficacy, tolerability and safety profile of DCV-TRIO, a twice-daily fixed-dose combination of daclatasvir, asunaprevir and beclabuvir approved in Japan for the treatment of genotype 1 HCV infection.Expert opinion: The DCV-TRIO combination achieved good response rates in genotype 1 patients (SVR12 ≥ 95% in naïve subtype 1b), independently from IL28B genotype, cirrhotic status and prior interferon exposure. On the other hand, unsatisfying response rates were reported in DAA-experienced patients and the risk of RAS selection should not be underestimated. Moreover, DCV-TRIO lacks differentiation from its earlier-launched DAA rivals, presents an inconvenient twice-daily dosing schedule and is not recommended in patients with advanced liver and kidney disease. All these drawbacks considerably limit its effective commercial potential. However, it can be a therapeutic option against HCV in tailored approaches according to the needs of different markets across the world.Abbreviations AE: adverse event; ALT: alanine aminotransferase; AST: aspartate aminotransferase; ASV: asunaprevir; AUC: area under the curve; BCRP: Breast Cancer Resistance Protein; BCV: boceprevir; BID: bis in die; CI: confidence intervals; CLcr: creatinine clearance; DAA: direct acting antivirals; DCV: daclatasvir; EC50: Half maximal effective concentration; GT: genotype; HCV: Hepatitis C virus; IFN: Interferon; NHL: non-Hodgkin lymphoma; OATP: Organic anion transporting polypeptides; OR: odds ratio; P-gp: P-glycoprotein; PK: pharmacokinetics; QD: quo die; RAS: resistance-associated substitutions; SVR: sustained virological response; USD: Unites States dollar.

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 ; Naganuma, Atsushi ; Takaguchi, Koichi ; 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.

100 Deals associated with Daclatasvir dihydrochloride/Asunaprevir/Beclabuvir hydrochloride

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External Link

KEGG	Wiki	ATC	Drug Bank
-	-	J05AP58	-

R&D Status

Approved

10 top approved records.

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

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Kidney Failure, Chronic	Phase 2	United States	Bristol Myers Squibb Co.	01 Apr 2014
Hepatitis C	Phase 2	France	Bristol Myers Squibb Co.	07 Dec 2013
Chronic hepatitis C genotype 1	Phase 2	France	Bristol Myers Squibb Co.	01 Dec 2013
Chronic hepatitis C genotype 1	Phase 2	Puerto Rico	Bristol Myers Squibb Co.	01 Dec 2013
Chronic hepatitis C genotype 1	Phase 2	Canada	Bristol Myers Squibb Co.	01 Dec 2013
Chronic hepatitis C genotype 1	Phase 2	Australia	Bristol Myers Squibb Co.	01 Dec 2013
Chronic hepatitis C genotype 1	Phase 2	United States	Bristol Myers Squibb Co.	01 Dec 2013

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Clinical Result

Indication

Phase

Evaluation

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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)	nankkrhubq(tonaygarza) = gzwflnfndw grismpqegj (lhxmrworcj, nyuworqhvq - yewexzounn) View more	-	29 May 2019
				DCV 3DAA+SOF (6 Weeks DCV 3DAA + SOF)	nankkrhubq(tonaygarza) = hcwwlbumoy grismpqegj (lhxmrworcj, syqxnsonrd - zahvtogcpc) View more
NCT02170727 (UNITY-4, Pubmed) Manual	Phase 3	Chronic hepatitis C genotype 1	169	Daclatasvir/asunaprevir/beclabuvir (treatment-naive patients)	(igmmkfypwv) = fjynlnmvhf mzrvplkbjs (oruaejxons, 94.9 - 99.8)	Positive	01 Dec 2017
				Daclatasvir/asunaprevir/beclabuvir (treatment-experienced patients)	(igmmkfypwv) = jbtkuhqexa mzrvplkbjs (oruaejxons, 88.8 - 100)
UEGW2017	Not Applicable	Chronic hepatitis C genotype 1	-	Daclatasvir, Asunaprevir, Beclabuvir	mcocuixhno(pyfxwyqvjy) = 14.3% (95%CI [12.0–16.9]) pffpojinhk (yiidntrjtd ) View more	-	01 Oct 2017
				Ribavirin