Delving into the Latest Updates on Emitasvir Phosphate with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Yimitasvir, Yimitasvir phosphate

+ [2]

Target

NS5A

Mechanism

NS5A inhibitors(Nonstructural protein 5A inhibitors)

Therapeutic Areas

Infectious DiseasesDigestive System Disorders

Active Indication

Hepatitis C, Chronic

Inactive Indication

Chronic hepatitis C genotype 1FibrosisKidney Failure, Chronic+ [2]

Originator Organization

YiChang HEC ChangJiang Pharmaceutical Co., Ltd.

Active Organization

YiChang HEC ChangJiang Pharmaceutical Co., Ltd.

Inactive Organization

Sunshine Lake Pharma Co., Ltd.

Dongguan HEC TaiGen Biopharmaceuticals Co., Ltd.

Drug Highest PhaseApproved

First Approval Date

CN (21 Dec 2020),

Hepatitis C, Chronic

RegulationSpecial Review Project (CN), Priority Review (CN)

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Structure

Molecular FormulaC49H61N8O10P

InChIKeyYHDAFJKFGSOUOV-KUNBUZFCSA-N

CAS Registry1959593-63-5

View All Structures (2)

Objective: To evaluate the drug-drug interactions and the tolerability of combined medication between yimitasvir phosphate capsules with sofosbuvir tablets, omeprazole magnesium enteric-coated tablets, and rosuvastatin calcium tablets in healthy volunteers. Methods: A randomized, open, and continuous administration design was used in trial 1 (yimitasvir phosphate capsules with sofosbuvir tablets). 28 subjects were randomly divided into two groups. A non-randomized, open design was used in trial 2 (yimitasvir phosphate capsules with omeprazole magnesium enteric-coated tablets), and included 42 subjects divided into three groups. The open design method was used in trial 3 (yimitasvir phosphate capsules with rosuvastatin calcium tablets), and included 14 subjects. The plasma concentrations of yimitasvir phosphate, sofosbuvir and their main metabolites GS-331007, omeprazole and rosuvastatin were validated by a liquid chromatography/tandem mass spectrometry (LC-MS/MS). The pharmacokinetic parameters were calculated by Phoenix winNonlin software. Results: (1) in trial 1, after single and co-administration, the 90% CI of sofosbuvir C(max) and AUC(0-tau) geometric mean ratio (GMR) were 152.0% (118.0% ~ 197.0%) and 230.0% (184.0% ~ 287.0%), with an increase of 52.0% and 130.0% compared to single dose of sofosbuvir, respectively. The 90% CI of GS-331007 C(max) GMR was 74.0% (67.5% ~ 81.2%) and reduced by 26% compared to single dose of sofosbuvir. (2) in trial 2, the 90% CI of C(max) GMR after yimitasvir single or co-administration at the same time, with a 4-hours interval, or with a 12- hours interval were 68.9% (44.5% ~ 106.7%) , 64.0% (43.8% ~ 93.6%) and 56.4%(38.9% ~ 81.9%), and the 90% CI of AUC(0-t) GMR were 68.6% (46.5% ~ 101.2%), 68.3% (47.6% ~ 98.0%) and 60.5% (41.8% ~ 87.5%), respectively. Compared with single dose of yimitasvir, the C(max) and AUC(0-t) were decreased by 31.1% and 31.4%, 36.0% and 31.7%, 43.6% and 39.5%, respectively. (3) In trial 3, after single and co-administration, the 90% CI of rosuvastatin C(max) and AUC(0-72) GMR were 172.4% (153.6% ~ 193.5%) and 158.0% (144.3% ~ 172.9%), respectively, with an increase of 74.9% and 60.5% compared to single dose of rosuvastatin. There were no serious adverse events and adverse events leading to withdrawal from the trial. Conclusion: Yimitasvir phosphate capsules have drug-drug interactions with sofosbuvir tablets, omeprazole magnesium enteric-coated tablets, and rosuvastatin calcium tablets.

28 Sep 2020·Journal of Clinical and Translational HepatologyQ2 · MEDICINE

Efficacy and Safety of All-oral Emitasvir and Sofosbuvir in Patients with Genotype 1b HCV Infections without Cirrhosis

Q2 · MEDICINE

Article

Author: Ren, Qingyun ; Xie, Hongming ; Yang, Daokun ; An, Ping ; Jin, Jinglan ; Yan, Xuebing ; Zheng, Sujun ; Luo, Lin ; Quan, Jun ; Wang, Guiqiang ; Zhao, Yingren ; Mao, Xiaorong ; Hou, Jinlin ; Sun, Tong ; Gong, Zuojiong ; Jia, Zhansheng ; Chen, Yongping ; Jia, Jidong ; Wang, Maorong ; Wu, Jie ; Huang, Rui ; Hu, Xiaoxuan ; Zhu, Yueyong ; Ma, Yingjie ; Tan, Youwen ; Ning, Qin ; Zhao, Caiyan ; Rao, Huiying ; Yang, Xingxiang ; Zhang, Lunli ; Lin, Minghua ; Xie, Qing ; Zhang, Fuchun ; Yang, Yongfeng ; Bai, Lang ; Yang, Dongliang ; Zhang, Yingjun ; Lin, Feng ; Wang, Jiefei ; Wei, Lai ; Xie, Wen

Background and Aims: Emitasvir is a new type of hepatitis C virus (HCV) nonstructural protein 5A (NS5A) inhibitor, and the data of phase 2 trial has shown emitasvir-sofosbuvir to have good safety and tolerance. We conducted this phase 3 trial to further verify the efficacy and safety. Methods: We evaluated the antiviral activity and safety of a 12-week regimen of emitasvir phosphate (100 mg) combined with sofosbuvir (400 mg) once daily in non-cirrhotic patients with genotype 1 HCV infection. The primary endpoint was a sustained virological response at 12 weeks (SVR12) after the end of treatment. Results: Of the 362 patients enrolled in the trial, 39.8% were male, 99.2% had HCV genotype 1b, 0.8% had genotype 1a and 79.8% were treatment-naïve. The average age was 47.2 years. All patients completed the treatment and follow-up. All 3 patients with genotype 1a achieved SVR. Two genotype 1b treatment-naïve patients experienced virologic relapse. The rate of SVR12 was 99.7% (358/359), and SVR24 was 99.4% (357/359) in genotype 1b. Overall, 36.2% had resistance-associated substitutions (RASs) in NS5A and 98.3% had RASs in NS5B at baseline. The RASs at baseline had no effect on the rates of response. Serious adverse events were reported in 16 patients and were not related to emitasvir-sofosbuvir. Most adverse events did not require therapy. Conclusions: The 12 weeks of treatment with emitasvir-sofosbuvir was a highly efficient and safe treatment for a wide range of patients with HCV genotype 1b infection without cirrhosis, who had not been treated or who had been treated with interferon-based regimen previously.

01 Jul 2019·Clinical Drug InvestigationQ4 · MEDICINE

Safety, Tolerability and Pharmacokinetics of Yimitasvir Phosphate Capsule, a Novel Oral Hepatitis C Virus NS5A Inhibitor, in Healthy Chinese Volunteers

Q4 · MEDICINE

Article

Author: Jia, Bo ; Zhang, Yingjun ; Zhao, Nan ; Zhao, Xia ; Xie, Ran ; Wang, Xingan ; Huang, Zhangma ; Cui, Yimin ; Zhao, Hong ; Ren, Qingyun ; Yan, Huan ; He, Bixia ; Li, Jing ; Xie, Hongming ; Luo, Lin

BACKGROUND AND OBJECTIVESYimitasvir is a novel oral hepatitis C virus non-structural protein 5A (NS5A) inhibitor. The aims of this first-in-human study were to evaluate the safety, tolerability and pharmacokinetics of single and multiple doses of yimitasvir in healthy adult Chinese volunteers and to assess the effect of food on yimitasvir pharmacokinetics.METHODSRandomized, double-blind, placebo-controlled, single-ascending-dose (30, 100, 200 and 400 mg) and multiple-ascending-dose (100 and 200 mg once daily for 7 days) studies were performed in 32 and 24 subjects, respectively, in male and female adults. Additionally, the effect of food on yimitasvir pharmacokinetics was assessed with a crossover study in 15 male subjects.RESULTSYimitasvir was absorbed slowly after oral administration with a median time to maximum plasma concentration (T_max) of 3.5-4.0 h. Increases in the maximum plasma concentration (C_max) and area under the concentration-time curve from 0 to the last measurable time point (AUC_0-t) were proportional to the dose of yimitasvir over a dose range of 30-100 mg, while increases were less than dose proportional over a dose range of 200-400 mg in part 1, indicating that absorption at the 200-mg dose was nearly saturated. The geometric mean terminal half-life of yimitasvir was 13.4-19.7 h in each cohort, supporting once-daily dosing. Faecal excretion of parent yimitasvir was the major route of elimination. Steady state was achieved following 5 days of dosing with minimal accumulation. A standardized high-fat meal decreased the rate and extent of absorption. All doses of yimitasvir were well tolerated.CONCLUSIONSYimitasvir, at single doses of 30-400 mg and multiple doses of 100-200 mg for 7 days, was well tolerated in healthy Chinese subjects. The results of this study formed the basis for the dosing schemes evaluated in a phase Ib study and subsequent phase II and phase III clinical studies.CLINICAL TRIAL REGISTRATIONThis study was registered at the China Food and Drug Administration (Registration numbers: 2014L02064 and 2014L02065) and at http://www.chictr.org.cn (Nos. CTR20140854, CTR20150048 and CTR20150123).

100 Deals associated with Emitasvir Phosphate

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External Link

KEGG	Wiki	ATC	Drug Bank
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R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Hepatitis C, Chronic	CN	YiChang HEC ChangJiang Pharmaceutical Co., Ltd.	21 Dec 2020

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Kidney Failure, Chronic	Phase 2	CN	Sunshine Lake Pharma Co., Ltd.	13 Apr 2021
Kidney Failure, Chronic	Phase 2	CN	YiChang HEC ChangJiang Pharmaceutical Co., Ltd.	13 Apr 2021
liver function failure	Phase 2	CN	Sunshine Lake Pharma Co., Ltd.	19 Oct 2020
Liver Injury	Phase 2	CN	Sunshine Lake Pharma Co., Ltd.	13 Oct 2020
Liver Injury	Phase 2	CN	YiChang HEC ChangJiang Pharmaceutical Co., Ltd.	13 Oct 2020
Chronic hepatitis C genotype 1	Phase 2	CN	Sunshine Lake Pharma Co., Ltd.	17 Apr 2018
Fibrosis	Discovery	CN	Dongguan HEC TaiGen Biopharmaceuticals Co., Ltd.	13 Jun 2019

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03487107 (Pubmed \| J Clin Transl Hepatol) Manual	Phase 3	Hepatitis C	362	Sofosbuvir+Emitasvir	(jovdbjrwxn) = xqievamdne swswvpdwql (qvzbmfhcng ) View more	Positive	28 Sep 2020