Elbasvir/grazoprevir: Difference between revisions
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Patents and Research |
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|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4925941/#B9 |
|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4925941/#B9 |
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|journal=International Journal of Hematology}}</ref> Zepatier is indicated for treatment with or without use of ribavirin, as well.<ref name="FDA">{{cite web|title=FDA approves Zepatier for treatment of chronic hepatitis C genotypes 1 and 4|url=http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm483828.htm|website=U.S. Food and Drug Administration|accessdate=31 January 2016}}</ref> |
|journal=International Journal of Hematology}}</ref> Zepatier is indicated for treatment with or without use of ribavirin, as well.<ref name="FDA">{{cite web|title=FDA approves Zepatier for treatment of chronic hepatitis C genotypes 1 and 4|url=http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm483828.htm|website=U.S. Food and Drug Administration|accessdate=31 January 2016}}</ref> |
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==Dosing== |
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===Side Effects=== |
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General side effects during treatment with Zepatier include feeling tired, nausea, and headache. Low red blood cell count has occurred when co-administered with ribavirin in some cases. Any lasting side effects should be brought up to a health care professional.<ref name="PI" /> |
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==Research== |
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===Patents=== |
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U.S. Patent No. 8871759 was published in 2014 for the specified compounds useful for hepatitis C virus NS5A inhibitors. The patent protects Merck’s formulation for the drug and its other associated salt forms, hydrates, solvates, prodrugs and isomers.<ref>{{cite patent |
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| country = US |
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| number = 8871759 |
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| status = patent |
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| title = Inhibitors of hepatitis C virus replication |
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| pubdate = 2014-10-28 |
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| fdate = 2010-03-25 |
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| pridate = 2009-03-27 |
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| invent1 = Craig A. Coburn |
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| assign1 = Merck Sharp & Dohme Corp. |
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}}</ref> U.S. Patent No. 7973040 was published in 2011. The patent protects the invention by Merck of the macrocyclic compound within the formula as an inhibitor for NS3 protease. The patent describes the formulation of the compound and its salts, along with its uses and potential implications as an HCV antiviral treatment. <ref>{{cite patent |
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| country = US |
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| number = 7973040 |
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| status = patent |
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| title = Macrocyclic quinoxaline compounds as HCV NS3 protease inhibitors |
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| pubdate = 2011-07-05 |
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| fdate = 2009-07-17 |
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| pridate = 2008-07-22 |
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| invent1 = Steven Harper, Vincenzo Summa, Nigel J. Liverton, John A. McCauley |
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| assign1 = Merck Sharp & Dohme Corp. |
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}} |
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</ref> |
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===Clinical Studies=== |
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A C-SALVAGE Phase 2 trial on safety and efficacy was reported in 2015. One randomized, open-label study was done on patients that had previous failure of a ribavirin/peginterferon treatment. SVR24 occurred in 96% of the patients with only 3 individuals relapsing.<ref>{{cite journal |
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|authors=Buti M, Gordon SC, Zuckerman E, Lawitz E, Calleja JL, Hofer H, Gilbert C, Palcza J, Howe AY, DiNubile MJ, Robertson MN, Wahl J, Barr E, Forns X |
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|date=2015 |
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|title=Grazoprevir, Elbasvir, and Ribavirin for Chronic Hepatitis C Virus Genotype 1 Infection After Failure of Pegylated Interferon and Ribavirin With an Earlier-Generation Protease Inhibitor: Final 24-Week Results From C-SALVAGE |
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|url=http://www.ncbi.nlm.nih.gov/pubmed/26371152 |
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|journal=Clinical Infectious Diseases |
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|volume=62 |
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|issue=32-6 }}</ref> |
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Additional Phase 2 trials were examined under the names: C-SWIFT, C-WORTHY, and C-WORTHY Coinfection. The first trial studied shorter dosing periods of 4, 6, or 8 weeks. C-SWIFT showed that the longer the time of treatment, the better the SVR results among patients.<ref>{{cite journal |
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|authors=Poordad F, Lawitz E, Gutierrez J, et al. |
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|date=2015 |
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|title=Grazoprevir/elbasvir + sofosbuvir in cirrhotic and noncirrhotic, treatment-naive patients with hepatitis C virus genotype 1 infection, for durations of 4, 6, or 8 weeks and genotype 3 infection for durations of 8 or 12 weeks. |
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|url=http://www.hepatitisc.uw.edu/page/treatment/drugs/elbasvir-grazoprevir |
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|journal=European Association for the Study of the Liver}}</ref> C-WORTHY study combined elbasvir with grazoprevir and additionally ribavirin in cases of cirrhosis. This demographic of patients is the most treatment refractory and the study showed that the ribavirin did not improve effects.<ref>{{cite journal |
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|authors=Lawitz E, Gane E, Pearlman B, et al. |
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|date=2015 |
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|title=Efficacy and safety of 12 weeks versus 18 weeks of treatment with grazoprevir (MK-5172) and elbasvir (MK-8742) with or without ribavirin for hepatitis C virus genotype 1 infection in previously untreated patients with cirrhosis and patients with previous null response with or without cirrhosis (C-WORTHY): a randomised, open-label phase 2 trial. |
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|url=http://www.ncbi.nlm.nih.gov/pubmed/25467591 |
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|journal=Lancet. |
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|volume=385 |
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|issue=1075-86 }}</ref> C-WORTHY Coinfection studied patients with HCV and HIV. Treatments of monoinfected patients and coinfected patients resulted in better SRV12 for the patients with coinfection and treated with ribrivin, too, at 97%.<ref>{{cite journal |
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|authors=Sulkowski M, Hezode C, Gerstoft J, et al. |
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|date=2015 |
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|title=Efficacy and safety of 8 weeks versus 12 weeks of treatment with grazoprevir (MK-5172) and elbasvir (MK-8742) with or without ribavirin in patients with hepatitis C virus genotype 1 mono-infection and HIV/hepatitis C virus co-infection (C-WORTHY): a randomised, open-label phase 2 trial. |
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|url=http://www.ncbi.nlm.nih.gov/pubmed/25467560 |
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|journal=Lancet. |
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|volume=385 |
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|issue=1087-97 }} |
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</ref> |
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Phase 3 study results of the drug were released in 2016. Results from C-EDGE IBLD show high rates of sustained virological response (SVR) after the completion of the prescribed treatment. This was examined 12-weeks after (SRV12). Safety profiles were consistent with previous studies. This study was a randomized, double-blind and placebo-controlled. 93% of the patients included in these studies showed SVR12 and had been cured of the virus.<ref>{{cite news |author=<!--Staff writer(s); no by-line.--> |title=Merck Announces Results From Phase 3 Studies of ZEPATIER™ (Elbasvir and Grazoprevir) in Chronic Hepatitis C Patient Populations at The International Liver Congress|url=http://www.businesswire.com/news/home/20160415005065/en/Merck-Announces-Results-Phase-3-Studies-ZEPATIER™|newspaper=Business Wire |agency=Berkshire Hathaway |date=2016-04-16 |access-date=2016-11-19}}</ref> |
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C-EDGE CO-STAR showed high SVR after 24-weeks. This studied reaffirmed results from studies of the previous year. The study was double-blind and placebo-controlled. Patients had HCV GT1, GT4, or GT6 and were on opioid therapy. Upwards of 96% of the patients achieved SVR24. This study contributed to the knowledge of the incidence of HCV reinfection in patients who receive drug injection of opioid treatments. This is a demographic that the medical community is typically reluctant to treat due to concerns of reinfection and compliance.<ref>{{cite news |author=<!--Staff writer(s); no by-line.--> |title=Merck Announces Results From Phase 3 Studies of ZEPATIER™ (Elbasvir and Grazoprevir) in Chronic Hepatitis C Patient Populations at The International Liver Congress|url=http://www.businesswire.com/news/home/20160415005065/en/Merck-Announces-Results-Phase-3-Studies-ZEPATIER™|newspaper=Business Wire |agency=Berkshire Hathaway |date=2016-04-16 |access-date=2016-11-19}}</ref> |
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==References== |
==References== |
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Revision as of 23:38, 20 November 2016
| Combination of | |
|---|---|
| Elbasvir | NS5A inhibitor |
| Grazoprevir | NS3/4A protease inhibitor |
| Clinical data | |
| Trade names | Zepatier |
| AHFS/Drugs.com | zepatier |
| Routes of administration | Oral (tablets) |
| ATC code | |
| Legal status | |
| Legal status |
|
Elbasvir/grazoprevir (trade name Zepatier ZEP-ah-teer) is a fixed-dose two drug combination for the treatment of hepatitis C, containing 50 mg elbasvir (a hepatitis C virus NS5A inhibitor) and 100 mg grazoprevir (an NS3/4A protease inhibitor). It is used to treat chronic HCV genotypes 1 or 4 infection in both treatment-naïve and treatment-experienced patients.[1]
Both elbasvir and grazoprevir were developed by Merck & Co. The drug was approved on January 28, 2016.[2]
Indications
Elbasvir/Grazoprevir received FDA approval in January 2016. Its indication is for treatment of chronic Hepatitis C Virus (HCV) of the genotypes (GT) 1 and 4 for adults. HCV is a global disease that infects upwards of 150 million people worldwide, most especially in older generations.[1] Hepatitis C causes inflammation of the liver that eventually leads to diminished liver function or even failure. The treatment of this virus with zepatier is now another approved treatment of the virus without requiring interferon use.[3] Zepatier is indicated for treatment with or without use of ribavirin, as well.[2]
Dosing
Side Effects
General side effects during treatment with Zepatier include feeling tired, nausea, and headache. Low red blood cell count has occurred when co-administered with ribavirin in some cases. Any lasting side effects should be brought up to a health care professional.[1]
Research
Patents
U.S. Patent No. 8871759 was published in 2014 for the specified compounds useful for hepatitis C virus NS5A inhibitors. The patent protects Merck’s formulation for the drug and its other associated salt forms, hydrates, solvates, prodrugs and isomers.[4] U.S. Patent No. 7973040 was published in 2011. The patent protects the invention by Merck of the macrocyclic compound within the formula as an inhibitor for NS3 protease. The patent describes the formulation of the compound and its salts, along with its uses and potential implications as an HCV antiviral treatment. [5]
Clinical Studies
A C-SALVAGE Phase 2 trial on safety and efficacy was reported in 2015. One randomized, open-label study was done on patients that had previous failure of a ribavirin/peginterferon treatment. SVR24 occurred in 96% of the patients with only 3 individuals relapsing.[6]
Additional Phase 2 trials were examined under the names: C-SWIFT, C-WORTHY, and C-WORTHY Coinfection. The first trial studied shorter dosing periods of 4, 6, or 8 weeks. C-SWIFT showed that the longer the time of treatment, the better the SVR results among patients.[7] C-WORTHY study combined elbasvir with grazoprevir and additionally ribavirin in cases of cirrhosis. This demographic of patients is the most treatment refractory and the study showed that the ribavirin did not improve effects.[8] C-WORTHY Coinfection studied patients with HCV and HIV. Treatments of monoinfected patients and coinfected patients resulted in better SRV12 for the patients with coinfection and treated with ribrivin, too, at 97%.[9]
Phase 3 study results of the drug were released in 2016. Results from C-EDGE IBLD show high rates of sustained virological response (SVR) after the completion of the prescribed treatment. This was examined 12-weeks after (SRV12). Safety profiles were consistent with previous studies. This study was a randomized, double-blind and placebo-controlled. 93% of the patients included in these studies showed SVR12 and had been cured of the virus.[10]
C-EDGE CO-STAR showed high SVR after 24-weeks. This studied reaffirmed results from studies of the previous year. The study was double-blind and placebo-controlled. Patients had HCV GT1, GT4, or GT6 and were on opioid therapy. Upwards of 96% of the patients achieved SVR24. This study contributed to the knowledge of the incidence of HCV reinfection in patients who receive drug injection of opioid treatments. This is a demographic that the medical community is typically reluctant to treat due to concerns of reinfection and compliance.[11]
References
- ^ a b c "ZEPATIER™ (elbasvir and grazoprevir) Tablets, for Oral Use. Full Prescribing Information" (PDF). Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. Retrieved 31 January 2016.
- ^ a b "FDA approves Zepatier for treatment of chronic hepatitis C genotypes 1 and 4". U.S. Food and Drug Administration. Retrieved 31 January 2016.
- ^ "Elbasvir/Grazoprevir: A Review of the Latest Agent in the Fight against Hepatitis C". International Journal of Hematology. 2016.
{{cite journal}}: Cite uses deprecated parameter|authors=(help) - ^ US patent 8871759, Craig A. Coburn, "Inhibitors of hepatitis C virus replication", published 2014-10-28, assigned to Merck Sharp & Dohme Corp.
- ^ US patent 7973040, Steven Harper, Vincenzo Summa, Nigel J. Liverton, John A. McCauley, "Macrocyclic quinoxaline compounds as HCV NS3 protease inhibitors", published 2011-07-05, assigned to Merck Sharp & Dohme Corp.
- ^ "Grazoprevir, Elbasvir, and Ribavirin for Chronic Hepatitis C Virus Genotype 1 Infection After Failure of Pegylated Interferon and Ribavirin With an Earlier-Generation Protease Inhibitor: Final 24-Week Results From C-SALVAGE". Clinical Infectious Diseases. 62 (32–6). 2015.
{{cite journal}}: Cite uses deprecated parameter|authors=(help) - ^ "Grazoprevir/elbasvir + sofosbuvir in cirrhotic and noncirrhotic, treatment-naive patients with hepatitis C virus genotype 1 infection, for durations of 4, 6, or 8 weeks and genotype 3 infection for durations of 8 or 12 weeks". European Association for the Study of the Liver. 2015.
{{cite journal}}: Cite uses deprecated parameter|authors=(help) - ^ "Efficacy and safety of 12 weeks versus 18 weeks of treatment with grazoprevir (MK-5172) and elbasvir (MK-8742) with or without ribavirin for hepatitis C virus genotype 1 infection in previously untreated patients with cirrhosis and patients with previous null response with or without cirrhosis (C-WORTHY): a randomised, open-label phase 2 trial". Lancet. 385 (1075–86). 2015.
{{cite journal}}: Cite uses deprecated parameter|authors=(help) - ^ "Efficacy and safety of 8 weeks versus 12 weeks of treatment with grazoprevir (MK-5172) and elbasvir (MK-8742) with or without ribavirin in patients with hepatitis C virus genotype 1 mono-infection and HIV/hepatitis C virus co-infection (C-WORTHY): a randomised, open-label phase 2 trial". Lancet. 385 (1087–97). 2015.
{{cite journal}}: Cite uses deprecated parameter|authors=(help) - ^ "Merck Announces Results From Phase 3 Studies of ZEPATIER™ (Elbasvir and Grazoprevir) in Chronic Hepatitis C Patient Populations at The International Liver Congress". Business Wire. Berkshire Hathaway. 2016-04-16. Retrieved 2016-11-19.
- ^ "Merck Announces Results From Phase 3 Studies of ZEPATIER™ (Elbasvir and Grazoprevir) in Chronic Hepatitis C Patient Populations at The International Liver Congress". Business Wire. Berkshire Hathaway. 2016-04-16. Retrieved 2016-11-19.
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