Delving into the Latest Updates on Elbasvir with Synapse

Clinical trials evaluating DAA have shown excellent rates of SVR and good safety profiles in patients with CHC infection. Real world data from TARGET, TRIO, IFI, DHCR, DALTON-C, as well as those cohorts from Japan, Taiwan and Korea further confirmed clinical trial findings of DAA in routine practice where populations are more complex. However, these populations are different from Chinese for different host and virus characteristics which limit the applicability of results to local practice.
As DAA launched in China since 2017, the availability of INF free DAA treatment will likely lead to better treatment outcome in routine practice, but there are currently no data available to test the hypothesis.
In clinical practice, the uptake of DAA regimen will depend on a combination of physician preference, patient's characteristics and drug access. This study will also identify how these three variables affect DAA regimen uptake.
This study to 1) characterize pts receiving IFN free DAA regimens, 2) represent common practice in China, 3) describe outcome of various INF free DAA therapy, and 4) confirm registration study results.

Start Date06 Mar 2019

Sponsor / Collaborator

Ruijin Hospital, Shanghai Jiaotong University School of Medicine

[+2]

EUCTR2018-002251-14-GB

/ Not yet recruitingPhase 4IIT

Localized on site testing and treatment of hepatitis C in homeless persons in London: a pilot non-randomised phase 4 interventional clinical trial of grazoprevir and elbasvir ± ribavirin in participants with genotype 1a, 1b or 4 to measure efficacy and adherence to treatment in a homeless population - ATTIC - Access To Treat in the Community

Start Date02 Jan 2019

Sponsor / Collaborator

King's College Hospital NHS Foundation Trust

NCT03037151

/ Unknown statusPhase 4IIT

Safety and Fibrosis Improvement of Grazoprevir and Elbasvir for HCV GT1 and GT6 With or Without HIV

This study will evaluate the safety and efficacy of combination treatment with grazoprevir + elbasvir for compensated cirrhotic participants with chronic genotype 1 (GT1) and genotype 6 (GT6) hepatitis C virus (HCV) infection with or without human immunodeficiency virus (HIV) infection.

Start Date01 Aug 2018

Sponsor / Collaborator

The HIV Netherlands Australia Thailand Research Collaboration

[+2]

100 Clinical Results associated with Elbasvir

Login to view more data

100 Translational Medicine associated with Elbasvir

Login to view more data

100 Patents (Medical) associated with Elbasvir

Login to view more data

719

Literatures (Medical) associated with Elbasvir

01 Dec 2024·HEPATOLOGY RESEARCH

Ratio of von Willebrand factor to ADAMTS13 is a useful predictor of esophagogastric varices progression after sustained virologic response in patients with hepatitis C virus‐related liver cirrhosis

Article

Author: Iwai, Satoshi ; Tsuji, Yuki ; Kitagawa, Koh ; Fujinaga, Yukihisa ; Akahane, Takemi ; Takaya, Hiroaki ; Kubo, Takahiro ; Tomooka, Fumimasa ; Shibamoto, Akihiko ; Namisaki, Tadashi ; Kawaratani, Hideto ; Suzuki, Junya ; Yoshiji, Hitoshi ; Nishimura, Norihisa ; Matsumoto, Masanori ; Kaji, Kosuke

Abstract:

Aim:

Esophagogastric varices (EGV) are a serious complication of hepatitis C virus (HCV)‐related liver cirrhosis (HCV‐LC). In most cases, portal hypertension improves after a sustained virologic response (SVR) is achieved with direct‐acting antiviral (DAA) treatment; however, in some cases, EGV exacerbation occurs after HCV elimination. We investigated whether von Willebrand factor (VWF) and a disintegrin‐like metalloproteinase with thrombospondin type‐1 motif 13 (ADAMTS13) can predict EGV progression with HCV‐LC after SVR achievement.

Methods:

This retrospective study enrolled 47 patients with HCV‐LC who achieved an SVR after DAA treatment. Eighteen patients experienced EGV progression after the SVR was achieved (EGV progression group). Twenty‐nine patients did not experience EGV progression after the SVR was achieved (non‐EGV progression group). Plasma VWF antigen levels and ADAMTS13 activity were measured the day before DAA treatment.

Results:

The EGV progression group had significantly higher plasma VWF antigen levels (p = 0.00331) and VWF‐to‐ADAMTS13 ratios (p = 0.000249) than the non‐EGV progression group. Multivariate logistic regression models found that a VWF‐to‐ADAMTS13 ratio >2.3 was the only risk factor for EGV progression after the SVR was achieved (hazard ratio [HR], 18.4; 95% confidence interval [CI], 3.08–109; p = 0.00138). During the observation period, patients with a VWF‐to‐ADAMTS13 ratio >2.3 had a significantly higher cumulative incidence of EGV progression after SVR achievement than patients with a VWF‐to‐ADAMTS13 ratio ≤2.3 (HR, 6.4; 95% CI, 1.78–22.96; p = 0.0044).

Conclusions:

The VWF‐to‐ADAMTS13 ratio before DAA treatment for HCV could predict EGV progression after SVR achievement.

01 Dec 2024·Combinatorial chemistry & high throughput screening

Evaluations of FDA-approved Drugs Targeting 3CLP of SARS-CoV-2 Employing a Repurposing Strategy

Article

Author: Ahmad, Syed Sayeed ; Khalid, Mohammad

Background::

The SARS-CoV-2 coronavirus (COVID-19) has raised innumerable global concerns, and few effective treatment strategies have yet been permitted by the FDA to lighten the disease burden. SARS-CoV-2 3C-like proteinase (3CLP) is a crucial protease and plays a key role in the viral life cycle, as it controls replication, and thus, it is viewed as a target for drug design.

Methods::

In this study, we performed structure-based virtual screening of FDA drugs approved during 2015-2019 (a total of 220 drugs) for interaction with the active site of 3CLP (PDB ID 6LU7) using AutoDock 4.2. We report the top ten drugs that outperform the reported drugs against 3CLP (Elbasvir and Nelfinavir), particularly Cefiderocol, having the highest affinity among the compounds tested, with a binding energy of -9.97 kcal/mol. H-bond (LYS102:HZ2-ligand: O49), hydrophobic (ligand-VAL104), and electrostatic (LYS102:NZ-ligand: O50) interactions were observed in the cefiderocol-3CLP complex. The docked complex was subjected to a 50 ns molecular dynamics study to check its stability, and stable RMSD and RMSF graphs were observed.

Results::

Accordingly, we suggest cefiderocol might be effective against SARS-CoV-2 and urge that experimental validation be performed to determine the antiviral efficacy of cefiderocol against SARS-CoV-2.

Discussion::

Along with these, cefiderocol is effective for treating respiratory tract pathogens and a wide range of gram-negative bacteria for whom there are limited therapeutic alternatives

Conclusion::

This article aimed to explore the FDA-approved drugs as a repurposing study against 3CLP for COVID-19 management.

28 Nov 2024·JOURNAL OF MEDICINAL CHEMISTRY

Proline Analogues in Drug Design: Current Trends and Future Prospects

Review

Author: Mykhailiuk, Pavel K. ; Kubyshkin, Vladimir

Proline analogues are versatile chemical building blocks that enable modular construction of small-molecule drugs and pharmaceutical peptides. Over the past 15 years, the FDA has approved over 15 drugs containing proline analogues in their structures, five in the last three years alone (daridorexant, trofinetide, nirmatrelvir, rezafungin, danicopan). This perspective offers an analysis of the most common types of proline analogues currently trending in drug design. We focus on examples of fluoroprolines, α-methylproline, bicyclic proline analogues, and aminoprolines, while also highlighting proline analogues that remain underrepresented. We supplement our analysis with physicochemical information regarding the specific molecular properties of these moieties. Additionally, we discuss several intriguing cases where nonproline residues were replaced with proline analogues as a strategy to eliminate unwanted hydrogen bond donor sites. In conclusion, we present some suggestions for the future exploration of this promising class of molecular entities in drug discovery.

100 Deals associated with Elbasvir

Login to view more data

External Link

KEGG	Wiki	ATC	Drug Bank
D10625	Elbasvir	J05AP10	DB11574

R&D Status

Approved

10 top approved records.

Login

to view more data

Indication	Country/Location	Organization	Date
Hepatitis C	JP	Merck Sharp & Dohme Corp.	28 Sep 2016

Developing

10 top R&D records.

Login

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Fibrosis	Phase 3	-	Merck Sharp & Dohme LLC	09 May 2014
Hepatitis C, Chronic	Phase 3	-	Merck Sharp & Dohme LLC	09 May 2014
Chronic Kidney Diseases	Phase 3	-	Merck Sharp & Dohme Corp.	17 Mar 2014
Acute hepatitis	Phase 2	FR	Merck Sharp & Dohme Corp.	31 May 2017
HIV Infections	Phase 2	FR	Merck Sharp & Dohme Corp.	31 May 2017
Chronic hepatitis C genotype 3	Phase 2	-	Merck Sharp & Dohme LLC	05 Jan 2016
Chronic hepatitis C genotype 2	Phase 2	-	Merck Sharp & Dohme Corp.	01 Oct 2013

Login to view more data

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02251990 (5172-067 \| C-CORAL, Pubmed)	Phase 3	Hepatitis C	152	Elbasvir/Grazoprevir 50mg/100mg	kksvmpafyc(uodqmlxcae) = ezwvfjisqa arulgvdjvh (rvzxjvuwyu )	Positive	01 Dec 2020
NCT03379506 (5172-079 \| MK-5172-079, CTgov)	Phase 2	Hepatitis C	57	GZR (Age Cohort 1: 12 to <18 Years: Mini and Expanded)	kprjgrbxzj(rjsnbhbone) = yrbksudeni folhlbcvgf (xnzglpibpe, htvgjdmmfj - chkjljtced) View more	-	17 Aug 2020
				GZR (Age Cohort 2: 7 to <12 Years: Mini and Expanded)	kprjgrbxzj(rjsnbhbone) = tngvnrpspw folhlbcvgf (xnzglpibpe, dpmdxytvjl - foizbwlsjv) View more
PITER (EASL2019)	Not Applicable	Hepatitis C, Chronic	312	Elbasvir/Grazoprevir	eumoqhvtac(bnrovavtan) = wozxhpykqg pszizszgii (ksikdnmlwd ) View more	Positive	13 Apr 2019
ZEPHYR (EASL2019)	Not Applicable	Hepatitis C, Chronic	183	Elbasvir/Grazoprevir (EBR/GZR)	lueizducvo(brptopisjm) = kfnnporefo suxdgrizrs (tfsqwvauig )	-	11 Apr 2019
NCT03111966 (Pubmed \| J Viral Hepat)	Not Applicable	Hepatitis C, Chronic	804	Elbasvir/Grazoprevir	nwekyvpgrq(okflorwzys) = Eighty patients experienced an AE, resulting in treatment discontinuation in three. zspnikgdnq (xacokgupkx )	Positive	01 Jan 2019
NCT02105701 \| NCT02105467 \| NCT01717326 \| NCT02105688 \| NCT02252016 \| NCT02203149 \| NCT02092350 \| NCT02115321 \| NCT02105662 \| NCT02358044 \| NCT02251990 (Pubmed)	Phase 2/3	Chronic hepatitis C genotype 1b	1,070	Elbasvir 50 mg + Grazoprevir 100 mg	hxevysiqps(iaixcvtukd) = yjkjmasrsh zcuozgxwew (xnxaatgjdx ) View more	-	01 May 2018
NCT01932762 (C-SCAPE, Pubmed \| J Viral Hepat)	Phase 2	Hepatitis C	-	EBR/GZR + RBV	feqasbzqcm(ncsulecnqo) = ilyijqeful fhzslpoqzs (nhjjmyrlzd )	-	01 May 2018
				GZR + RBV	feqasbzqcm(ncsulecnqo) = dojbdctbir fhzslpoqzs (nhjjmyrlzd )
NCT00998985 \| NCT01532973 (Pubmed \| Clin Ther)	Phase 1	Hepatitis C	-	Elbasvir	kklzyoyxwc(ylvpiasgfz) = okihilillz jwtcrjyrwd (yhuvhpmkzs )	-	01 May 2018
				Grazoprevir	kklzyoyxwc(ylvpiasgfz) = krgysdnqzo jwtcrjyrwd (yhuvhpmkzs )
NCT02601573 (MK-5172-083 \| 5172-083 \| C-ISLE, CTgov)	Phase 2	Chronic hepatitis C genotype 3	101	Elbasvir+Grazoprevir+Sofosbuvir+Ribavirin (Arm 1: HCV GT3 TN EBG/GZR+SOF+RBV 8 Weeks)	xpkvriurdm(zwxftxmdzm) = cnjbwmlxny favucdrnbh (woizcwbmyf, auhpocqbpl - lfzlmwryzo) View more	-	13 Nov 2017
				Grazoprevir+Sofosbuvir+Elbasvir (Arm 2: HCV GT3 TN EBG/GZR+SOF 12 Weeks)	xpkvriurdm(zwxftxmdzm) = anxrrgggzq favucdrnbh (woizcwbmyf, vrzktmuayu - yvbmfmqaml) View more
NCT01717326 (5172-035, Pubmed \| J Viral Hepat)	Phase 2	Hepatitis C	573	EBR+GZR+RBV for 12 weeks	cadwitnjmf(cssmysajyc) = xztehgmuvv ukusbtjuwc (qerpxbmtvv, 23.1 - 68.5)	-	01 Oct 2017
				EBR+GZR+RBV for 18 weeks	cadwitnjmf(cssmysajyc) = qngrywiqed ukusbtjuwc (qerpxbmtvv, 34.0 - 78.2)