Delving into the Latest Updates on Uprifosbuvir with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Uprifosbuvir (USAN/INN)

+ [2]

Target

NS5B polymerase

Mechanism

NS5B polymerase inhibitors(Hepatitis C virus NS5B RNA-dependent RNA polymerase inhibitors)

Therapeutic Areas

Infectious DiseasesDigestive System Disorders

Active Indication-

Inactive Indication

Chronic hepatitis C genotype 1Hepatitis C

Originator Organization

Merck & Co., Inc.

Active Organization-

Inactive Organization

Merck GmbH

Merck Sharp & Dohme Corp.

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC22H29ClN3O9P

InChIKeySFPFZQKYPOWCSI-KHFYHRBSSA-N

CAS Registry1496551-77-9

This is a nonrandomized, multi-site, open-label trial to evaluate a novel two-drug combination regimen (uprifosbuvir [MK-3682] 450 mg + ruzasvir [RZR; MK-8408] 180 mg once daily [q.d.] for 12 weeks) in male and female treatment-naïve (TN) or treatment-experienced (TE) participants with chronic hepatitis C virus (HCV) infection genotype (GT) GT1, GT2, GT3, GT4, GT5, or GT6 who have not previously received HCV direct-acting antiviral (DAA) therapy. Cirrhotic (C) and non-cirrhotic (NC) participants with and without human immunodeficiency virus (HIV) co-infection will be enrolled.

Start Date16 Nov 2016

Sponsor / Collaborator

Merck Sharp & Dohme Corp.

NCT02759315

/ TerminatedPhase 2

A Phase II, Open-Label Clinical Trial to Study the Efficacy and Safety of the Combination Regimen of MK-3682 + MK-8408 in Subjects With Chronic HCV Genotype 1, 2, 3, 4, 5 or 6 Infection

This study is an open-label, multi-center trial to evaluate the novel 2-drug regimen of uprifosbuvir (MK-3682) 450 mg and ruzasvir (MK-8408) 60 mg in participants with chronic hepatitis C virus (HCV) genotype (GT)1, GT2, GT3, GT4, GT5, or GT6 infection. The impact of the study treatment regimen on the percentage of participants with undetectable HCV ribonucleic acid [RNA] 12 weeks after completing study treatment (SVR12) will be evaluated.

Start Date03 May 2016

Sponsor / Collaborator

Merck Sharp & Dohme Corp.

100 Clinical Results associated with Uprifosbuvir

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100 Translational Medicine associated with Uprifosbuvir

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100 Patents (Medical) associated with Uprifosbuvir

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17

Literatures (Medical) associated with Uprifosbuvir

01 Aug 2023·Virology

Differential activity of nucleotide analogs against tick-borne encephalitis and yellow fever viruses in human cell lines

Article

Author: Galli, Andrea ; Bukh, Jens ; Binderup, Alekxander ; Fossat, Nicolas ; Fahnøe, Ulrik ; Scheel, Troels K H ; Rivera-Rangel, Lizandro René ; Mikkelsen, Lotte S ; Fernandez-Antunez, Carlota ; Ramirez, Santseharay

With no approved antiviral therapies, the continuous emergence and re-emergence of tick-borne encephalitis virus (TBEV) and yellow fever virus (YFV) is a rising concern. We performed head-to-head comparisons of the antiviral activity of available nucleos(t)ide analogs (nucs) using relevant human cell lines. Eight existing nucs inhibited TBEV and/or YFV with differential activity between cell lines and viruses. Remdesivir, uprifosbuvir and sofosbuvir were the most potent drugs against TBEV and YFV in liver cells, but they had reduced activity in neural cells, whereas galidesivir retained uniform activity across cell lines and viruses. Ribavirin, valopicitabine, molnupiravir and GS-6620 exhibited only moderate antiviral activity. We found antiviral activity for drugs previously reported as inactive, demonstrating the importance of using human cell lines and comparative experimental assays when screening the activity of nucs. The relatively high antiviral activity of remdesivir, sofosbuvir and uprifosbuvir against TBEV and YFV merits further investigation in clinical studies.

01 Jul 2021·CPT: Pharmacometrics & Systems PharmacologyQ3 · MEDICINE

Understanding effect site pharmacology of uprifosbuvir, a hepatitis C virus nucleoside inhibitor: Case study of a multidisciplinary modeling approach in drug development

Q3 · MEDICINE

ArticleOA

Author: Gao, Wei ; Miller, Randy ; Rizk, Matthew L. ; Post, Teun M. ; Kesisoglou, Filippos ; van den Berg, Paul ; Ahsman, Maurice J. ; Arrington, Leticia

AbstractUprifosbuvir is a uridine nucleoside monophosphate prodrug inhibitor of the hepatitis C virus NS5B RNA polymerase. To quantitatively elucidate key metabolic pathways, assess the link between unmeasurable effect site concentrations and viral load reduction, and evaluate the influence of intrinsic and extrinsic factors on pharmacokinetics and pharmacodynamics, a model‐informed drug development (MIDD) framework was initiated at an early stage. Originally scoped as a modeling effort focused on minimal physiologically based pharmacokinetic and covariate analyses, this project turned into a collaborative effort focused on gaining a deeper understanding of the data from drug metabolism, biopharmaceutics, pharmacometrics, and clinical pharmacology perspectives. This article presents an example of the practical execution of a MIDD‐based, cooperative multidisciplinary modeling approach, creating a model that grows along with the team's integrated knowledge. Insights gained from this process could be used in forming optimal collaborations between disciplines in drug development for other investigative compounds.

01 Feb 2020·BMJ Case Reports

Glecaprevir/pibrentasvir+sofosbuvir: an optimal retreatment strategy in the setting of HCV NS5A resistance

Article

Author: Conway, Brian ; Yamamoto, Leo ; Alimohammadi, Arshia

Some individuals do not achieve a cure of their hepatitis C virus (HCV) infection due to non-adherence or resistance associated substitutions. Salvage options that are optimised for resistance profiles are essential. We report a 56-year-old Caucasian man with fatigue, depression and confusion in the setting of untreated HCV genotype 3a infection. He received ruzasvir and uprifosbuvir for 12 weeks within a clinical trial. The patient relapsed 4 weeks after the end of treatment and at this time resistance testing showed multiple resistances including a NS5A Y93H mutation. Given that this mutation confers resistance to first line salvage options, sofosbuvir and glecaprevir/pibrentasvir was used for 12 weeks and the patient was cured of HCV infection 12 weeks after the end of treatment. This shows that sofosbuvir and glecaprevir/pibrentasvir is a viable, effective option for second line/salvage therapy of HCV infection in the setting of resistance to NS5A inhibitors with the Y93H mutation.

100 Deals associated with Uprifosbuvir

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External Link

KEGG	Wiki	ATC	Drug Bank
D10996	Uprifosbuvir	-	DB15206

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Hepatitis C	Phase 2	GB	Merck GmbH	-
Hepatitis C	Phase 2	BE	Merck GmbH	-
Hepatitis C	Phase 2	CA	Merck GmbH	-
Hepatitis C	Phase 2	BE	Merck GmbH	-
Hepatitis C	Phase 2	AT	Merck GmbH	-
Hepatitis C	Phase 2	AT	Merck GmbH	-
Hepatitis C	Phase 2	GB	Merck GmbH	-
Hepatitis C	Phase 2	CA	Merck GmbH	-
Hepatitis C	Phase 2	IL	Merck GmbH	-
Hepatitis C	Phase 2	IL	Merck GmbH	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02956629 (C-BREEZE 2 \| MK-3682-041 \| 3682-041, Pubmed \| J Viral Hepat) Manual	Phase 2	Hepatitis C, Chronic	282	Ruzasvir+uprifosbuvir	(agtziucllq) = crwyxoaufd gusdyymuxd (fdaoeudune ) View more	Positive	01 Sep 2019
NCT02759315 (3682-035 \| MK-3682-035, Pubmed \| J Viral Hepat)	Phase 2	Hepatitis C	160	Ruzasvir 60 mg + Uprifosbuvir 450 mg	(wuqrrckghj) = ebycbwolpn fxdpcsiqjx (dzgukyhbpi )	-	01 Jun 2019
NCT02956629 (C-BREEZE 2 \| MK-3682-041 \| 3682-041, CTgov)	Phase 2	Hepatitis C, Chronic	282	Uprifosbuvir+Ribavirin+Ruzasvir (HCV GT1)	trzkmuipgu(iaqadberbx) = swxayauzhk qfwimvtvok (upqyuaqwxa, upibyojoxw - oqmlejevcw) View more	-	26 Dec 2018
				Uprifosbuvir+Ribavirin+Ruzasvir (HCV GT2)	trzkmuipgu(iaqadberbx) = sckcabixwh qfwimvtvok (upqyuaqwxa, astkmzwtmw - krdnaxguli) View more
NCT02666352 (3682-029, CTgov)	Phase 1	Hepatitis C, Chronic	24	Uprifosbuvir+Ruzasvir (Moderate HI Participants)	migpbbwemz(btksjancbp) = pjbenxtbgn qsvfjexjee (pznixotuyj, pvrwkzikbw - imjruvyfmc) View more	-	17 Sep 2018
				Uprifosbuvir+Ruzasvir (Severe HI Participants)	migpbbwemz(btksjancbp) = ayulxkkebu qsvfjexjee (pznixotuyj, bqpzueaxsh - yegxluvbmr) View more
NCT02759315 (3682-035 \| MK-3682-035, CTgov)	Phase 2	Chronic hepatitis C genotype 1	160	Uprifosbuvir 450 mg+Ruzasvir 60 mg (GT1: Uprifosbuvir 450 mg + Ruzasvir 60 mg)	dzmiudokhu(sluxojbrbp) = plnbvewxox mnfetkzoyb (sonbullxht, rmpnipgtfo - adzcuqpkvp) View more	-	06 Aug 2018
				Uprifosbuvir 450 mg+Ruzasvir 60 mg (GT2: Uprifosbuvir 450 mg + Ruzasvir 60 mg)	dzmiudokhu(sluxojbrbp) = zbfgrknjfs mnfetkzoyb (sonbullxht, ynwkdkelio - kqfiaruklu) View more