elbasvir (MK-8742) News

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|||||||||| ombitasvir (ABT-267) / AbbVie, Ledipasvir (GS-5885) / Gilead, elbasvir (MK-8742) / Merck (MSD)
Journal: In silico Antivirus Repurposing and its Modification to Organoselenium Compounds as SARS-CoV-2 Spike Inhibitors. (Pubmed Central) - Jun 6, 2023
The best-modified ligand was chosen by analyzing the ADME-Tox property, RMSD value and binding energy value. The best three unmodified ligands, Ombitasvir, Elbasvir and Ledipasvir, have a binding energy value of -15.8065, -15.3842 and -15.1255 kcal mol1, respectively and the best three modified ligands ModL1, ModL2 and ModL3 has a binding value of -15.6716, -13.9489 and -13.2951 kcal mol1, respectively with an RMSD value of 1.7109

|||||||||| Torisel (temsirolimus) / Pfizer, elbasvir (MK-8742) / Merck (MSD)
Journal: Potential drug candidates as P-glycoprotein inhibitors to reverse multidrug resistance in cancer: an in silico drug discovery study. (Pubmed Central) - Mar 9, 2023
The pharmacokinetic properties of the identified drugs were predicted and demonstrated good ADMET characteristics. Overall, these results indicated that valspodar, dactinomycin, elbasvir, temsirolimus, and sirolimus hold promise as prospective P-gp inhibitors and warrant further invitro/invivo investigations.

|||||||||| elbasvir (MK-8742) / Merck (MSD)
Journal: In-silico docking studies of selected phytochemicals against papain like protease of SARS-Cov-2. (Pubmed Central) - Dec 20, 2022
Phytochemicals such as Tinosponone, Rhoifolin, Rosmanol, Berberin, Nimbin and two other existing drugs Elbasvir and Declatasvir showed higher inhibitory potential in terms of higher binding affinities...Molecular Dynamics simulation of Tinosponone with PLpro has proved the stability and validity of the binding with RMSD value in range of 0.2 nm when it was run for 50 ns using GROMACS. Therefore, Tinosponone could be considered as a potential inhibitor of PLpro of SARS CoV-2.

|||||||||| Review, Journal: A Review on Analytical Strategies for the Assessment of Recently Approved Direct Acting Antiviral Drugs. (Pubmed Central) - Nov 9, 2022
These approaches include spectroscopic, chromatographic, capillary electrophoretic, voltametric and nuclear magnetic resonance methods that have been reported during this period. Moreover, the analytical instrumentation and methods used in determination of these DAADs will be illustrated in tabulated forms.

|||||||||| glecaprevir (ABT-493) / AbbVie, elbasvir (MK-8742) / Merck (MSD)
Journal: Targeting allosteric pockets of SARS-CoV-2 main protease M. (Pubmed Central) - Aug 24, 2022
Suitable choice of drugs in catalytic and allosteric pockets appear to be essential for combination therapy. Current study, based on docking and extensive set of MD simulations, finds the combination of Elbasvir, Glecaprevir and Ritonavir to be a viable candidate for further experimental drug testing/pharmacophore design for M.Communicated by Ramaswamy H. Sarma.

|||||||||| Viracept (nelfinavir) / ViiV Healthcare, Roche, elbasvir (MK-8742) / Merck (MSD)
FDA event, Journal: Evaluations of FDA-approved drugs targeting 3CLP of SARS-CoV-2 employing a repurposing strategy. (Pubmed Central) - Aug 22, 2022
Current study, based on docking and extensive set of MD simulations, finds the combination of Elbasvir, Glecaprevir and Ritonavir to be a viable candidate for further experimental drug testing/pharmacophore design for M.Communicated by Ramaswamy H. Sarma. The aim of this article was to explore the FDA approved drugs as repurposing study against 3CLP for COVID-19 management.

|||||||||| Venclexta (venetoclax) / Roche, AbbVie, Ledipasvir (GS-5885) / Gilead, elbasvir (MK-8742) / Merck (MSD)
Journal: Applying polypharmacology approach for drug repurposing for SARS-CoV2. (Pubmed Central) - May 3, 2022
Four drugs namely venetoclax, tirilazad, acetyldigitoxin, and ledipasvir have been selected as potential candidates. The online version contains supplementary material available at 10.1007/s12039-022-02046-0.

|||||||||| Preclinical, Journal: Evaluation of the Potency of Anti-HIV and Anti-HCV Drugs to Inhibit P-Glycoprotein Mediated Efflux of Digoxin in Caco-2 Cell Line and Human Precision-Cut Intestinal Slices. (Pubmed Central) - Feb 27, 2022
However, abacavir, dolutegravir, maraviroc, sofosbuvir, tenofovir disoproxil fumarate, and zidovudine had no inhibitory effect...More inhibitors were identified when using digoxin as the ABCB1 probe substrate than when using rhodamine123. However, both approaches had limitations, indicating that inhibitory potency should be tested with at least these two ABCB1 probes.

|||||||||| elbasvir (MK-8742) / Merck (MSD)
Clinical, Real-world evidence: Treatment of hepatitis C virus infection in people with opioid use disorder: a real-world study of elbasvir/grazopr… https://t.co/O4hfUzsZH1 (Twitter) - Jan 28, 2022

|||||||||| elbasvir (MK-8742) / Merck (MSD)
Journal: Elucidating the role of N440K mutation in SARS-CoV-2 spike - ACE-2 binding affinity and COVID-19 severity by virtual screening, molecular docking and dynamics approach. (Pubmed Central) - Dec 15, 2021
To find a potential inhibitor against mutant N440K SARS-CoV-2, a virtual screening process was carried out and found ZINC169293961, ZINC409421825 and ZINC22060839 as the best binding energy compounds. Communicated by Ramaswamy H. Sarma.

|||||||||| elbasvir (MK-8742) / Merck (MSD)
Journal: Ligand-based quantitative structural assessments of SARS-CoV-2 3CL inhibitors: An analysis in light of structure-based multi-molecular modeling evidences. (Pubmed Central) - Dec 7, 2021
The binding modes of those repurposed drugs were also justified by the molecular docking, molecular dynamics (MD) simulation, and binding energy calculations conducted by several groups of researchers. This current work, therefore, may be able to find out important structural parameters to accelerate the COVID-19 drug discovery processes in the future.

|||||||||| beclabuvir (BMS-791325) / BMS, grazoprevir (MK-5172) / Merck (MSD), elbasvir (MK-8742) / Merck (MSD)
FDA event, Journal: Re-Purposing of Hepatitis C Virus FDA Approved Direct Acting Antivirals as Potential SARS-CoV-2 Protease Inhibitors. (Pubmed Central) - Nov 25, 2021
Furthermore, the correlation between binding energies were found in accord with the results from the reported ICs for some DAAs. Overall, the current study provides insight to combat COVID-19 using FDA-approved DAAs as repurposed drugs.

|||||||||| Clinical, Journal: Efficacy of NS5A inhibitors against unusual and potentially difficult-to-treat HCV subtypes commonly found in sub Saharan Africa and South East Asia. (Pubmed Central) - Nov 17, 2021
This study also shows the ineffectiveness of the first generation NS5A inhibitors against 6u and 6v, and confirms the inherent resistance of 3b and 3g to most NS5A inhibitors. Clinical studies to confirm in vivo sensitivity to NS5A inhibitors are urgently needed so that rational, effective treatment strategies may be developed for unusual subtypes.

|||||||||| elbasvir (MK-8742) / Merck (MSD)
FDA event, Journal: Repurposing of FDA-approved Drugs against Active Site and Potential Allosteric Drug Binding Sites of COVID-19 Main Protease. (Pubmed Central) - Oct 22, 2021
Energy decomposition calculations per residue elucidate key binding residues stabilizing the ligands that can further serve to design pharmacophores. This systematic and efficient computational analysis successfully determines ivermectine, diosmin and selinexor currently subjected to clinical trials, and further proposes bromocriptine, elbasvir as M inhibitor candidates to be evaluated against SARS-CoV-2 infections.

|||||||||| [VIRTUAL] DIRECT ANTIVIRALS CAN ACHIEVE A CURE IN ALL PATIENTS WITH CHRONIC HEPATITIS C DUE TO GENOTYPE 5. (FRENCH MULTICENTRE STUDY.) () - Oct 21, 2021 - Abstract #AASLD2021AASLD_1188;
A high SVR12, 99% (138/139) in intention to treat and 100% (138/138) per protocol, was achieved in HCV GT5 patients treated with a DAA-regimen . This cohort shows that the combination treatments of SOF/LDV, SOF/VEL and GLE/PIB are very efficient in patients infected with HCV GT5.

|||||||||| elbasvir (MK-8742) / Merck (MSD)
Clinical, Journal, HEOR: Cost-effectiveness of a "treat-all" strategy using Direct-Acting Antivirals (DAAs) for Japanese patients with chronic hepatitis C genotype 1 at different fibrosis stages. (Pubmed Central) - Oct 2, 2021
This cohort shows that the combination treatments of SOF/LDV, SOF/VEL and GLE/PIB are very efficient in patients infected with HCV GT5. Our results suggested that administration of DAA treatment for all Japanese patients with genotype 1 CHC regardless of their liver fibrosis stage would be cost-effective under ordinary conditions.

|||||||||| grazoprevir (MK-5172) / Merck (MSD), elbasvir (MK-8742) / Merck (MSD)
Invention of grazoprevir: A macrocyclic HCV NS3/4a protease inhibitor for the treatment of the hepatitis C virus infection (Room: Thomas Murphy Ballroom Sections 3 & 4) - Aug 13, 2021 - Abstract #ACSFall2021ACS_Fall_9247;
The utilization of a molecular modeling-based strategy to identify the novel P2-P4 macrocyclic series along with a flexible and reliable synthetic route which enabled rapid synthesis of diverse analogs, was key to the ultimate successful invention of grazoprevir. While the key steps leading to the design of grazoprevir will be the focus, this presentation will also highlight the development of a scalable synthetic route and several of the key clinical studies which demonstrated the robust activity of the fixed-dose combination ZEPATIER.

|||||||||| elbasvir (MK-8742) / Merck (MSD)
Journal: Electron Donor-Acceptor Capacity of Selected Pharmaceuticals against COVID-19. (Pubmed Central) - Jul 4, 2021
The results I present here show Valrubicin as the best electron acceptor (an anticancer drug with three F atoms in its structure) and elbasvir as the best electron donor (antiviral for chronic hepatitis C)...Ivermectin and Molnupiravir are two powerful COVID-19 drugs that are not good electron acceptors, and the fact that they are not as effective oxidants as other molecules may be an advantage...These results represent a further advance on the road towards understanding the action mechanisms of drugs used as possible treatments for COVID-19. Looking ahead, clinical studies are needed to define the importance of antioxidants in treating COVID-19.

|||||||||| elbasvir (MK-8742) / Merck (MSD)
FDA event, Journal: An insight into the inhibitory mechanism of phytochemicals and FDA-approved drugs on the ACE2-Spike complex of SARS-CoV-2 using computational methods. (Pubmed Central) - May 20, 2021
The phytochemicals identified belonged to Withania somnifera, Swertia chirayita, Tinospora cordifolia and Rutin DAB10, fulvestrant, elbasvir from FDA. The online version contains supplementary material available at 10.1007/s11696-021-01680-1.

|||||||||| elbasvir (MK-8742) / Merck (MSD)
Preclinical, Journal: Combined in silico and in vitro approaches identified the antipsychotic drug lurasidone and the antiviral drug elbasvir as SARS-CoV2 and HCoV-OC43 inhibitors. (Pubmed Central) - Apr 29, 2021
Results showed that certain drugs displayed activity for both viruses at a similar inhibitory concentration, while others were specific. In particular, the antipsychotic drug lurasidone and the antiviral drug elbasvir showed promising activity in the low micromolar range against both viruses with good selectivity index.

|||||||||| [VIRTUAL] Direct antivirals can achieve a cure in all patients with chronic hepatitis C due to genotype 5. A French multicentre study. (Poster area) - Apr 9, 2021 - Abstract #EASLILC2021EASL_ILC_1227;
A high SVR12, 99% (138/139) in intention to treat and 100% (138/138) per protocol, was achieved in HCV GT5 patients treatedwith a DAA-regimen. This cohort shows that the combination treatments of SOF/LDV, SOF/VEL and GLE/PIB are very efficient in patients infected with HCV GT5.

|||||||||| Clinical, Review, Journal: Direct-Acting Antivirals interactions with opioids, alcohol or illicit drugs in HCV-infected patients. (Pubmed Central) - Mar 24, 2021
Based on pharmacological considerations, neither efficacy loss, nor adverse drug event associated with detrimental interaction are expected with opioids, stimulants, cannabinoids, and ethanol. In summary, our literature review shows that the interaction potential of DAA with most opioids and illicit drugs is limited and should not be a hurdle to the initiate DAA.

|||||||||| elbasvir (MK-8742) / Merck (MSD)
Journal: Drug repositioning to target NSP15 protein on SARS-CoV-2 as possible COVID-19 treatment. (Pubmed Central) - Mar 14, 2021
We found from the docking analysis that the antiviral drugs: Paritaprevir and Elbasvir, currently both approved for hepatitis C treatment which showed some of the lowest free binding energy values were considered as repositioning drugs to combat SARS-CoV-2. Furthermore, molecular dynamics simulations of the Apo and Holo-Nsp15 systems were performed in order to get insights about the stability of these protein-ligand complexes.

|||||||||| elbasvir (MK-8742) / Merck (MSD)
Journal: CSF3 Is a Potential Drug Target for the Treatment of COVID-19. (Pubmed Central) - Feb 9, 2021
Further, we screened potential drugs targeting CSF3 by MOE; the top 50 drugs were screened by flexible docking and rigid docking, with 37 intersections. Two antiviral drugs (Elbasvir and Ritonavir) were included; Elbasvir and Ritonavir formed van der Waals (VDW) interactions with surrounding residues to bind with CSF3, and Elbasvir and Ritonavir significantly inhibited CSF3 protein expression.

|||||||||| Journal: Raltegravir, Indinavir, Tipranavir, Dolutegravir, and Etravirine against main protease and RNA-dependent RNA polymerase of SARS-CoV-2: A molecular docking and drug repurposing approach. (Pubmed Central) - Dec 18, 2020
Two antiviral drugs (Elbasvir and Ritonavir) were included; Elbasvir and Ritonavir formed van der Waals (VDW) interactions with surrounding residues to bind with CSF3, and Elbasvir and Ritonavir significantly inhibited CSF3 protein expression. This study suggests that the screened small molecule antiviral drugs Raltegravir, Indinavir, Tipranavir, Dolutegravir, and Etravirine could serve as potential drugs for the treatment of COVID-19 with further validation studies.

|||||||||| elbasvir (MK-8742) / Merck (MSD)
Journal: Epidemic history and baseline resistance to NS5A-specific direct acting drugs of hepatitis C virus in Spain. (Pubmed Central) - Dec 16, 2020
Previously, the prevalence of NS5A resistance-associated substitutions (RASs) to elbasvir, a new direct-acting antiviral (DAA) against the NS5A viral protein was assessed by our group before its introduction into clinical use in Spain...A moderate level of baseline RASs to NS5A-DAAs with marked differences among regions was observed. Close surveillance of response to treatment with DAAs will be important.

|||||||||| grazoprevir (MK-5172) / Merck (MSD), velpatasvir (GS-5816) / Gilead, elbasvir (MK-8742) / Merck (MSD)
Clinical, Journal: Impact of novel NS5A resistance-associated substitutions of hepatitis C virus detected in treatment-experienced patients. (Pubmed Central) - Oct 22, 2020
However, these viruses were susceptible to grazoprevir, ribavirin and sofosbuvir. Thus, combination regimens with these reagents may eradicate viruses harboring A92K or P32del.

|||||||||| [VIRTUAL] Choice of Recommended Treatment Options for Patients with Hepatitis C Genotype 1 in Moscow, Russian Federation () - Oct 3, 2020 - Abstract #ISPOREU2020ISPOR-EU_1904;
In genotype 1b patients independent of subgroups top-4 regimens were: daclatasvir+sofosbuvir±ribavirin (€ 5938), grasoprevir+elbasvir (€ 5964), dasabuvir+ombitasvir+paritaprevir+ritonavir (€ 6219) and velpatasvir+sofosbuvir (€6223). As a result of a transparent and scientific-based analysis were selected treatment regimens for patients with chronic HCV genotype 1 recommended for reimbursement in Moscow in 2020.

|||||||||| Journal: Features of resistance-associated substitutions after failure of multiple direct-acting antiviral regimens for hepatitis C. (Pubmed Central) - Aug 22, 2020
R30H and L31-RAS in NS5A were frequently detected after failure of regimens including daclatasvir...S282T RAS in NS5B was detected in 3.9% of ledipasvir/sofosbuvir failures...We investigated RASs after failure of various treatments for chronic hepatitis C, and found that more complicated RASs accumulated in the viral genome with successive failed treatments. The highly resistant P32del RAS at NS5A region was uniquely found in patients for whom DAA treatments had failed, and was linked to the presence and absence of specific RASs.

|||||||||| velpatasvir (GS-5816) / Gilead, Daklinza (daclatasvir) / BMS, elbasvir (MK-8742) / Merck (MSD)
Preclinical, Journal: Combinations of two drugs among NS3/4A inhibitors, NS5B inhibitors and non-selective antiviral agents are effective for hepatitis C virus with NS5A-P32 deletion in humanized-liver mice. (Pubmed Central) - Jul 2, 2020
The highly resistant P32del RAS at NS5A region was uniquely found in patients for whom DAA treatments had failed, and was linked to the presence and absence of specific RASs. Therapies combining at least two drugs among NS3/4A inhibitors, NS5B inhibitors and non-selective antiviral agents may be effective for HCV-infected patients with NS5A-P32del.

|||||||||| Ledipasvir (GS-5885) / Gilead, Daklinza (daclatasvir) / BMS, elbasvir (MK-8742) / Merck (MSD)
Journal: Pre-treatment antiviral resistance in Australians with chronic hepatitis C: prevalence of NS3 and NS5A resistance data in the state of New South Wales. (Pubmed Central) - Jul 2, 2020
This is the largest study of HCV antiviral drug resistance in Australia, which differs from resistance prevalence in the USA. The results provide valuable data on the baseline prevalence of HCV resistance, which can be used in future to monitor for increasing antiviral resistance.

|||||||||| elbasvir (MK-8742) / Merck (MSD)
Journal: Fast Identification of Possible Drug Treatment of Coronavirus Disease -19 (COVID-19) Through Computational Drug Repurposing Study. (Pubmed Central) - Jul 1, 2020
I found that one hotspot residue HIS41, is a conserved residue across many viruses including SARS-Cov, SARS-Cov-2, MERS-Cov, and HCV. The findings of this study can facilitate rational drug design targeting the SARS-Cov-2 main protease.

|||||||||| Daklinza (daclatasvir) / BMS, Sovaldi (sofosbuvir) / Gilead, elbasvir (MK-8742) / Merck (MSD)
Journal, Combination therapy: Optimization of a sensitive and robust strategy for micellar electrokinetic chromatographic analysis of sofosbuvir in combination with its co-formulated hepatitis C antiviral drugs. (Pubmed Central) - Jun 19, 2020
Based on our previous work with "pseudostationary-ion exchanger sweeping", we use this strategy to develop a sensitive, reliable and robust method for the analysis of the newly-FDA approved hepatitis C antiviral drugs namely; sofosbuvir (SOV), daclatasvir (DAC), ledipasvir (LED) and velpatasvir (VEP) in their pure forms and co-formulated pharmaceutical dosage forms using micellar electrokinetic chromatography (MEKC) as a separation method...The selectivity of the developed method for determination of the studied compounds in their pharmaceutical dosage forms or in the presence of ribavirin (RIB) or elbasvir (ELB), which are other prescribed medications in the treatment regimen of patients with hepatitis C virus infection, is demonstrated. It is shown that with acidic sample matrix and basic BGE, an efficient and precise approach was designed in which analyte adsorption on the capillary wall was minimized while keeping repeatable peak height, peak area and migration time together with the highest possible enrichment efficiency.

|||||||||| Journal: Resistance analysis of genotype 3 HCV indicates subtypes inherently resistant to NS5A inhibitors. (Pubmed Central) - Jun 18, 2020
The paired A30K + L31M substitutions occur in all patients with gt3b and gt3g virus. In vitro analysis suggests that these subtypes may be inherently resistant to all approved NS5A Inhibitors for gt3 HCV.

|||||||||| elbasvir (MK-8742) / Merck (MSD)
Journal: Estimated Changes in Manufacturer and Health Care Organization Revenue Following List Price Reductions for Hepatitis C Treatments. (Pubmed Central) - Jun 15, 2020
List price reductions for hepatitis C treatments may have increased drug manufacturer net revenues, owing in part to lower discounts provided under the 340B program and the high share of sales subject to those discounts. Policymakers should consider the role of 340B discounts when evaluating policies to reduce drug spending.

|||||||||| elbasvir (MK-8742) / Merck (MSD)
Clinical, Journal: Glycemic Control after Initiating Direct-Acting Antiviral Agents in Patients with Hepatitis C Virus and Type 2 Diabetes Mellitus Using the United States Integrated Healthcare System. (Pubmed Central) - Jun 6, 2020
Both groups had statistically significant reductions in HbA1c when comparing the mean change in average HbA1c pre-versus post-DAA agent. Patients who achieved SVR had a greater absolute reduction in HbA1c by 0.04%; however, this was not statistically significant.

|||||||||| pibrentasvir (ABT-530) / AbbVie, glecaprevir (ABT-493) / AbbVie, elbasvir (MK-8742) / Merck (MSD)
[VIRTUAL] HCV DAA treatment failure is associated to hepatocellular carcinioma presence (Poster Area) - May 30, 2020 - Abstract #EASLILCI2020EASL-ILC-I-833;
Background and Aims: Sustained Virological Responses (SVR) are nowaday obtained in real life settings, in almost 98-99% of HCV-infected patients using 8 or 12W schedules and 2nd generation DAAs (glecaprevir/pibrentasvir, sofosbuvir/velpatasvir and elbasvir/gazoprevir). The presence of HCC and cirrhosis independently increase the risk of HCV treatment failure with DAAs

|||||||||| Clinical, Journal: Comparison of Naturally Occurring Resistance-Associated Substitutions Between 2008 and 2016 in Chinese Patients with Chronic Hepatitis C Virus Infection. (Pubmed Central) - Dec 26, 2019
The presence of HCC and cirrhosis independently increase the risk of HCV treatment failure with DAAs The frequency of NS5A RASs in 2016 was significantly higher than that in 2008, especially at the L28 and Y93 substitution positions, which may be due to their better fitness compared with wild-type viruses.

|||||||||| elbasvir (MK-8742) / Merck (MSD)
Journal: Evolutionary pathways to NS5A inhibitor resistance in genotype 1 hepatitis C virus. (Pubmed Central) - Oct 8, 2019
Here, we adopted a highly accurate, ultra-deep primer ID sequencing approach to intensively study serial changes in the NS5A-coding region of HCV in gt-1a- and gt-1b-infected subjects receiving a short course of monotherapy with the NS5A inhibitor, elbasvir...Consistent with this, cell culture studies with gt-1a and gt-1b reporter viruses and replicons demonstrated that Y93H confers a much greater loss of replicative fitness in gt-1a than gt-1b virus, and that L31M/V both compensates for the loss of fitness associated with Q30R (but not Y93H) and also boosts drug resistance. These observations show how differences in the impact of RASs on drug resistance and replicative fitness influence the evolution of gt-1a and gt-1b viruses during monotherapy with an antiviral targeting NS5A.

|||||||||| ITALIAN REAL LIFE EXPERIENCE OF RESISTANCE-GUIDED RETREATMENT IN HCV INFECTED PATIENTS WHO PREVIOUSLY FAILED A NS5A INHIBITOR-CONTAINING REGIMEN (Hynes Convention Center, Room 302) - Sep 29, 2019 - Abstract #AASLD2019AASLD_1812;
Overall, SVR after resistance-guided retreatment was very high, with the exception of the SOF/VEL retreatment. Our results show how resistance test after failure may be useful to optimize the retreatment strategies.

|||||||||| Zepatier (grazoprevir/elbasvir) / Merck (MSD), elbasvir (MK-8742) / Merck (MSD)
Clinical, PK/PD data, Journal: No Pharmacokinetic Interactions Between Elbasvir or Grazoprevir and Buprenorphine/Naloxone in Healthy Participants and Participants Receiving Stable Opioid Agonist Therapy. (Pubmed Central) - Sep 28, 2019
The GMRs (90% CI) for EBR and GZR AUC in the absence/presence of BUP/NAL were 1.22 (0.98-1.52) and 0.86 (0.63-1.18). In conclusion, no dose adjustment for BUP/NAL, EBR, or GZR is required for patients with HCV infection receiving EBR/GZR and BUP/NAL maintenance therapy.

|||||||||| Zepatier (grazoprevir/elbasvir) / Merck (MSD), elbasvir (MK-8742) / Merck (MSD)
Clinical, PK/PD data, Journal: No Pharmacokinetic Interactions Between Elbasvir or Grazoprevir and Methadone in Participants Receiving Maintenance Opioid Agonist Therapy. (Pubmed Central) - Sep 28, 2019
The GMRs for EBR and GZR AUC in participants receiving methadone relative to a healthy historical cohort not receiving methadone were 1.20 (90% CI, 0.94-1.53) and 1.03 (90% CI, 0.76-1.41), respectively. These results indicate that no dose adjustment is required for individuals with HCV infection receiving stable methadone therapy and the EBR/GZR fixed-dose regimen.

|||||||||| Journal: Expert opinion on the management of renal manifestations of chronic HCV infection. (Pubmed Central) - Sep 28, 2019
In patients with severe kidney impairment, sofosbuvir-free regimens are preferred because sofosbuvir accumulation has been associated with a progressive worsening of renal function. In this Review, we provide our expert opinion on the current HCV treatment paradigm and highlight the remaining issues that need to be overcome to improve the treatment of HCV in this population.

|||||||||| Journal: Direct-Acting Antivirals to Prevent Vertical Transmission of Viral Hepatitis C: When Is the Optimal Time to Treat? (Pubmed Central) - Sep 26, 2019
In this Review, we provide our expert opinion on the current HCV treatment paradigm and highlight the remaining issues that need to be overcome to improve the treatment of HCV in this population. Data to determine the best treatment point along the pregnancy-pediatric continuum are limited; however, given the lack of human data for use of DAAs during pregnancy, low rate of VT, high rate of spontaneous pediatric clearance, and recent approval of DAAs for pediatric patients, treatment of chronically infected children seems to be the optimal strategy currently.

|||||||||| elbasvir (MK-8742) / Merck (MSD)
Clinical, Journal, Real-World Evidence: Elbasvir plus grazoprevir for patients with chronic hepatitis C genotype 1: A multicenter, real-world cohort study focusing on chronic kidney disease. (Pubmed Central) - Sep 26, 2019
EBR plus GZR for HCV genotype 1 was highly effective with a low rate of adverse effects, regardless of CKD status. In addition, liver parameters and complement levels improved longitudinally.

|||||||||| grazoprevir (MK-5172) / Merck (MSD), elbasvir (MK-8742) / Merck (MSD)
Journal: Interplay of Amino Acid Residues at Positions 28 and 31 in NS5A Defines Resistance Pathways in HCV GT2. (Pubmed Central) - Sep 19, 2019
Ruzasvir, a potent, pan-genotype NS5A inhibitor successfully inhibited replicons bearing GT2 resistance-associated substitutions (RASs) at positions 28 and 31. The studies demonstrate crosstalk between amino acids at positions 28 and 31 in NS5A modulate inhibitor potency and may impact treatment outcomes in some HCV GT2-infected patients.

|||||||||| grazoprevir (MK-5172) / Merck (MSD), Sovaldi (sofosbuvir) / Gilead, elbasvir (MK-8742) / Merck (MSD)
Clinical, Journal: Direct-Acting Antiviral Prophylaxis in Kidney Transplantation From Hepatitis C Virus-Infected Donors to Noninfected Recipients: An Open-Label Nonrandomized Trial. (Pubmed Central) - Aug 9, 2019
P4
Recipients of kidneys from donors with genotype 1 infection continued receiving GZR-EBR for 12 weeks after transplantation; those receiving organs from donors with genotype 2 or 3 infection had sofosbuvir, 400 mg, added to GZR-EBR for 12 weeks of triple therapy...If confirmed in larger studies, this strategy should markedly expand organ options and reduce mortality for kidney transplant candidates without HCV infection. Merck Sharp & Dohme Corp.

|||||||||| elbasvir (MK-8742) / Merck (MSD)
Journal: The Discovery of MK-6169, A Potent Pan-genotype Hepatitis C Virus NS5A Inhibitor with Optimized Activity Against Common Resistance-Associated Substitutions. (Pubmed Central) - May 29, 2019
SAR studies around the combination of changes to both the valine and aminal carbon region of elbasvir lead to the discovery of a series of compounds with substantially improved potency against common resistance-associated substitutions in the major genotypes, as well as good pharmacokinetics in both rat and dog. Through further optimization of key leads from this effort, MK-6169 (21) was discovered as a pre-clinical candidate for further development.

|||||||||| elbasvir (MK-8742) / Merck (MSD)
Clinical, P3 data, Journal, HEOR: Elbasvir plus grazoprevir in patients with hepatitis C virus infection and stage 4-5 chronic kidney disease: clinical, virological, and health-related quality-of-life outcomes from a phase 3, multicentre, randomised, double-blind, placebo-controlled trial. (Pubmed Central) - Sep 27, 2018
P2/3
Through further optimization of key leads from this effort, MK-6169 (21) was discovered as a pre-clinical candidate for further development. These data add to the growing body of clinical evidence for the fixed-dose combination regimen of elbasvir plus grazoprevir for 12 weeks and support use of this therapy in patients with HCV genotype 1 infection and stage 4-5 chronic kidney disease.

|||||||||| grazoprevir (MK-5172) / Merck (MSD)
PK/PD data, Journal: The Effect of Hepatic Impairment on the Pharmacokinetics of Grazoprevir, a Hepatitis C Virus Protease Inhibitor. (Pubmed Central) - Jul 22, 2018
No dose adjustment is required for GZR in people with HCV with mild HI. GZR is contraindicated in those with moderate or severe HI (Child-Pugh B or C), as they may have significantly increased GZR exposures that may lead to increased risk of transaminase elevations.



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