Delving into the Latest Updates on Vedroprevir with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

VDV, Vedroprevir (USAN), GS-9451

Target

NS3/NS4A

Action

inhibitors

Mechanism

NS3/NS4A inhibitors(Hepatitis C virus serine protease, NS3/NS4A inhibitors)

Therapeutic Areas

Infectious DiseasesDigestive System DisordersOther Diseases

Active Indication-

Inactive Indication

Chronic hepatitis C genotype 1FibrosisHepatitis C, Chronic

Originator Organization

Gilead Sciences, Inc.

Active Organization-

Inactive Organization

Gilead Sciences, Inc.

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC45H60ClN7O9S

InChIKeyOTXAMWFYPMNDME-FQQWJMKMSA-N

CAS Registry1098189-15-1

This study is to evaluate the antiviral efficacy, safety, and tolerability of combination therapy with ledipasvir/sofosbuvir (LDV/SOF) fixed-dose combination (FDC) + vedroprevir (VDV) ± ribavirin (RBV) for 8 weeks in treatment-experienced adults with chronic genotype 1 hepatitis C virus (HCV) infection and cirrhosis.

Start Date01 Jul 2014

Sponsor / Collaborator

Gilead Sciences, Inc.

NCT01805882

/ CompletedPhase 2IIT

A Pilot Study to Evaluate the Safety and Efficacy of Multiple Anti-HCV Combination Therapy in Chronically Infected Hepatitis C Patients

Background:
- GS-7977, GS-5885, GS-9669, and GS-9451 are new drugs for treating hepatitis C virus (HCV) infection. GS-7977 may help treat the infection when used with other treatments like interferon therapy. GS-5885, and GS-9669, and GS-9451 also lower the amount of HCV in the body. Researchers want to see whether GS-7977 can be combined with any of the other three drugs to treat HCV infection. Some participants will take GS-7977 and GS-5885. Others will take GS-7977, GS-5885 and GS-9669 or GS-7977, GS-5885 and GS-9451.
Objectives:
- To see whether GS-7977 with GS-5885 alone or in combination with either GS-9669 or 9451 can be used to treat HCV infection.
Eligibility:
Individuals at least 18 years of age who have chronic HCV infection and have never been treated for it.
Individuals at least 18 years of age who have chronic HCV infection and have not responded to interferon therapy.
Individuals at least 18 years of age who have chronic HCV infection with advanced liver disease and have never been treated for HCV
Design:
Participants will be screened with a physical exam and medical history. Blood samples will be collected. A liver biopsy may also be performed.
Some participants will take the two study drugs and some will take three study drugs. Those who take GS-7977 and GS-5885 will have one daily tablet named fixed dose combination or FDC. Those who take GS-7977 and CS-9669 will have three daily tablets taken once daily. Those who take GS-7977 and GS-5885 and GS-9451 will take 2 pills once a day. GS-7977 and GS-5885 will be combined in one pill and GS-9451 will be in another pill.
Treatment will be monitored with frequent blood tests. These tests will check liver function and the level of HCV infection. Participants may have other blood tests as needed for treatment.
Participants will have 4, 6 or 12 weeks of treatment depending on which study drugs are scheduled to take. After they complete their schedule, they will stop treatment with the study drugs. They may also have another liver biopsy.
Participants will have regular follow-up visits over the next 48 weeks. They will have physical exams and provide blood samples....

Start Date01 Jan 2013

Sponsor / Collaborator

National Institute of Allergy & Infectious Diseases

EUCTR2011-000456-42-BG

/ Not yet recruitingNot Applicable

A Phase 2b, Randomized, Double-Blind, Placebo-Controlled Trial Evaluating Response Guided Therapy with GS-5885 Alone or in Combination with GS-9451 with Peginterferon Alfa 2a and Ribavirin in Treatment Naïve Subjects with Chronic Genotype 1 Hepatitis C Virus Infection

Start Date17 Jan 2012

Sponsor / Collaborator

Gilead Sciences, Inc.

100 Clinical Results associated with Vedroprevir

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100 Translational Medicine associated with Vedroprevir

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100 Patents (Medical) associated with Vedroprevir

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29

Literatures (Medical) associated with Vedroprevir

01 Feb 2018·Journal of viral hepatitisQ2 · MEDICINE

Nonstructural protein 5A resistance profile in patients with chronic hepatitis C treated with ledipasvir‐containing regimens without sofosbuvir

Q2 · MEDICINE

Article

Author: Miller, M. D. ; Hedskog, C. ; Kitrinos, K. M. ; Worth, A. ; Corsa, A. C. ; Mo, H. ; Brainard, D. M.

Summary:

The study aimed to evaluate the effects of baseline hepatitis C virus (HCV) nonstructural protein 5A (NS5A) resistance‐associated substitutions (RASs) on sustained virologic response to ledipasvir (LDV)‐containing regimens in the absence of sofosbuvir (SOF) in patients with HCV genotype (GT) 1 infection across 6 phase 2 clinical studies. We analysed data from 1103 patients who received either LDV + vedroprevir (NS3 protease inhibitor) + tegobuvir (NS5B inhibitor) ± ribavirin or LDV + ribavirin + pegylated interferon. Population sequencing of HCV NS5A was performed at baseline and at virologic failure from patient plasma samples. Of 1045 patients with available baseline sequences, 747 (67.7%) had GT1a, and 298 (26.9%) had GT1b infection. The overall prevalence of NS5A RASs at baseline was 9.4%; 7.6% (57/747) and 13.8% (41/298) of patients with GT1a and GT1b infection, respectively. The majority of GT1a‐infected patients with NS5A RASs at baseline had a single NS5A RAS (78.9%) at NS5A positions K24R, M28T, Q30H/L, L31M and Y93H/N/C/S. The spectrum of NS5A RASs detected in GT1b patients was much less diverse compared to GT1a patients, with all patients harbouring a single NS5A RAS either L31M or Y93H/C. For patients treated with LDV‐containing regimens in the absence of SOF, the presence of baseline NS5A RASs was associated with low SVR rates. In patients with virologic failure, nearly all had either pre‐existing and/or emergent NS5A RASs: 287/287 (100%) and 40/42 (95.2%) patients with GT1a and GT1b infection, respectively. Three novel NS5A substitutions were identified as emergent NS5A RASs: K26E and S38F in GT1a; and L31I in GT1b. In conclusion, the presence of NS5A RASs at baseline reduced the SVR rate in patients treated with LDV in combination vedroprevir + tegobuvir ± ribavirin or ribavirin + pegylated interferon. Virologic failure was associated with the detection of NS5A RASs in nearly all patients. These results suggest that the resistance barrier may differ depending on HCV drug combination and may be more important than that of the individual DAAs.

02 Dec 2017·Expert opinion on investigational drugsQ2 · MEDICINE

Vedroprevir in the management of hepatitis C virus infection

Q2 · MEDICINE

Review

Author: Kottilil, Shyamasundaran ; Abutaleb, Ameer

INTRODUCTION:

Hepatitis C Virus (HCV) is a chronic infection of the liver and the leading cause of liver failure and liver transplantation worldwide. While prior HCV therapies were prolonged and had variable success rates, the advent of direct-acting antivirals (DAAs) has dramatically improved HCV therapy with minimal side effects, shorter treatment durations, and higher cure rates. Areas covered: In this paper, we review the literature discussing the use of Vedroprevir (GS-9451) in treatment of HCV in a variety of patient populations. Articles accessible on MEDLINE/PubMed were reviewed to provide context on chemistry, pharmacology, and efficacy of Vedroprevir in HCV treatment. Expert opinion: Vedroprevir is highly effective in reducing treatment duration in combination with other DAAs without compromising treatment success rates. GS-9451 is insufficient as HCV monotherapy due to low threshold for development of high level of resistance and must be combined with other DAAs to achieve sustained virologic response (SVR).

01 Oct 2017·Journal of invertebrate pathologyQ3 · BIOLOGY

Relative abundance of deformed wing virus, Varroa destructor virus 1, and their recombinants in honey bees (Apis mellifera) assessed by kmer analysis of public RNA-Seq data

Q3 · BIOLOGY

Article

Author: Cornman, Robert Scott

Deformed wing virus (DWV) is a major pathogen of concern to apiculture, and recent reports have indicated the local predominance and potential virulence of recombinants between DWV and a related virus, Varroa destructor virus 1 (VDV). However, little is known about the frequency and titer of VDV and recombinants relative to DWV generally. In this study, I assessed the relative occurrence and titer of DWV and VDV in public RNA-seq accessions of honey bee using a rapid, kmer-based approach. Three recombinant types were detectable graphically and corroborated by de novo assembly. Recombination breakpoints did not disrupt the capsid-encoding region, consistent with previous reports, and both VDV- and DWV-derived capsids were observed in recombinant backgrounds. High abundance of VDV kmers was largely restricted to recombinant forms. Non-metric multidimensional scaling identified genotypic clusters among DWV isolates, which was corroborated by read mapping and consensus generation. The recently described DWV-C lineage was not detected in the searched accessions. The data further highlight the utility of high-throughput sequencing to monitor viral polymorphisms and statistically test biological predictors of titer, and point to the need for consistent methodologies and sampling schemes.

100 Deals associated with Vedroprevir

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External Link

KEGG	Wiki	ATC	Drug Bank
D10408	-	-	DB12037

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Fibrosis	Phase 2	United States	Gilead Sciences, Inc.	01 Jul 2014
Hepatitis C, Chronic	Phase 2	United States	Gilead Sciences, Inc.	01 Sep 2011
Hepatitis C, Chronic	Phase 2	Canada	Gilead Sciences, Inc.	01 Sep 2011
Chronic hepatitis C genotype 1	Phase 2	United States	Gilead Sciences, Inc.	01 Oct 2010
Chronic hepatitis C genotype 1	Phase 2	Austria	Gilead Sciences, Inc.	01 Oct 2010
Chronic hepatitis C genotype 1	Phase 2	Belgium	Gilead Sciences, Inc.	01 Oct 2010
Chronic hepatitis C genotype 1	Phase 2	France	Gilead Sciences, Inc.	01 Oct 2010
Chronic hepatitis C genotype 1	Phase 2	Germany	Gilead Sciences, Inc.	01 Oct 2010
Chronic hepatitis C genotype 1	Phase 2	Netherlands	Gilead Sciences, Inc.	01 Oct 2010
Chronic hepatitis C genotype 1	Phase 2	Poland	Gilead Sciences, Inc.	01 Oct 2010

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01805882 (CTgov)	Phase 2	Hepatitis C, Chronic	229	Sofosbuvir+ledipasvir (D Retx: HCV GT-1, Re-Treatment, 12 Wks Sofosbuvir, Ledipasvir)	irpglxhhrh = oeofxcosey ngpadqvebt (xjmzguxoiv, cnzvxnjypb - nntzwnvmrq) View more	-	11 Apr 2017
				Sofosbuvir+ledipasvir (D: HCV GT-1, Tx-relapsed, 12 Wks Sofosbuvir/Ledipasvir)	irpglxhhrh = nzwzcrmjws ngpadqvebt (xjmzguxoiv, vgdkxrgldc - vfzimktspp) View more
NCT02226549 (CTgov)	Phase 2	Chronic hepatitis C genotype 1 \| Fibrosis	47	LDV/SOF+VDV (LDV/SOF+VDV)	sdoemmelvf = gqunjrqtuf haqkyazoxe (mntkhrcpgi, lbtupmllde - lqkepzxvgk) View more	-	04 Mar 2016
				LDV/SOF+VDV+RBV (LDV/SOF+VDV+RBV)	sdoemmelvf = fdfhbshams haqkyazoxe (mntkhrcpgi, gioiypraad - kfaoukmlgm) View more