The safety and efficacy of elbasvir and grazoprevir in participants with hepatitis C virus genotype 1b infection

Journal of Gastroenterology

Volumn 53, Issue 5, 2018, Pages 679-688

  Zeuzem, Stefan ^a   Serfaty, Lawrence ^b   Vierling, John ^c   Cheng, Wendy ^d   George, Jacob ^e   Sperl, Jan ^f   Strasser, Simone ^g   Kumada, Hiromitsu ^h   Hwang, Peggy ⁱ   Robertson, Michael ⁱ   Wahl, Janice ⁱ   Barr, Eliav ⁱ   Talwani, Rohit ⁱ   Platt, Heather ⁱ  

^a UNIVERSITY HOSPITAL FRANKFURT   (Germany)

^b HÔPITAL SAINT ANTOINE   (France)

^c BAYLOR COLLEGE OF MEDICINE   (United States)

^d ROYAL PERTH HOSPITAL   (Australia)

^e UNIVERSITY OF SYDNEY   (Australia)

^f INSTITUTE FOR CLINICAL AND EXPERIMENTAL MEDICINE   (Czech Republic)

^g ROYAL PRINCE ALFRED HOSPITAL   (Australia)

^h TORANOMON HOSPITAL   (Japan)

ⁱ MERCK RESEARCH LABORATORIES   (United States)

Author keywords

Hepatitis; Retrospective; Therapy

Indexed keywords

ALANINE AMINOTRANSFERASE; ELBASVIR; ELBASVIR PLUS GRAZOPREVIR; GRAZOPREVIR; NONSTRUCTURAL PROTEIN 5A; 2-(PYRROLIDIN-2-YL)-5-(2-(4-(5-(PYRROLIDIN-2-YL)-1H-IMIDAZOL-2-YL)PHENYL)BENZOFURAN-5-YL)-1H-IMIDAZOLE; ANTIVIRUS AGENT; BENZOFURAN DERIVATIVE; IMIDAZOLE DERIVATIVE; MK-5172; NS-5 PROTEIN, HEPATITIS C VIRUS; QUINOXALINE DERIVATIVE; VIRAL PROTEIN;

ADULT; AGED; ALANINE AMINOTRANSFERASE BLOOD LEVEL; AMINO ACID SUBSTITUTION; ANTIVIRAL RESISTANCE; ANTIVIRAL THERAPY; ARTICLE; CHRONIC HEPATITIS C; COMPENSATED LIVER CIRRHOSIS; DRUG EFFICACY; DRUG SAFETY; DRUG TREATMENT FAILURE; FEMALE; HEPATITIS C VIRUS SUBTYPE 1B; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; MAJOR CLINICAL STUDY; MALE; MIDDLE AGED; MIXED INFECTION; PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; RELAPSE; RETROSPECTIVE STUDY; SIDE EFFECT; SUSTAINED VIROLOGIC RESPONSE; TREATMENT DURATION; TREATMENT OUTCOME; UNSPECIFIED SIDE EFFECT; VIRUS LOAD; ADOLESCENT; COMPLICATION; GENETICS; GENOTYPE; HEPACIVIRUS; LIVER CIRRHOSIS; PATHOPHYSIOLOGY; VIROLOGY; YOUNG ADULT;

ADOLESCENT; ADULT; AGED; ANTIVIRAL AGENTS; BENZOFURANS; CLINICAL TRIALS, PHASE II AS TOPIC; CLINICAL TRIALS, PHASE III AS TOPIC; COINFECTION; DRUG RESISTANCE, VIRAL; FEMALE; GENOTYPE; HEPACIVIRUS; HEPATITIS C, CHRONIC; HIV INFECTIONS; HUMANS; IMIDAZOLES; LIVER CIRRHOSIS; MALE; MIDDLE AGED; QUINOXALINES; RETROSPECTIVE STUDIES; SUSTAINED VIROLOGIC RESPONSE; VIRAL LOAD; VIRAL NONSTRUCTURAL PROTEINS; YOUNG ADULT;

EID: 85040672387     PISSN: 09441174     EISSN: 14355922     Source Type: Journal    
DOI: 10.1007/s00535-018-1429-3     Document Type: Article

References (28)

1. Gower E, Estes C, Blach S, et al. Global epidemiology and genotype distribution of the hepatitis C virus infection. J Hepatol. 2014;61(Suppl 1):S45–57.
2. AASLD/IDSA HCV Guidance Panel. Hepatitis C guidance: AASLD-IDSA recommendations for testing, managing, and treating adults infected with hepatitis C virus. Hepatology. 2015;62(3):932–54.
3. European Association for the Study of the Liver. EASL recommendations on treatment of hepatitis C 2015. J Hepatol. 2015;63(1):199–236.
4. Kowdley KV, Gordon SC, Reddy KR, for the ION-3 Investigators, et al. Ledipasvir and sofosbuvir for 8 or 12 weeks for chronic HCV without cirrhosis. N Engl J Med. 2014;370(20):1879–88.
5. Andreone P, Colombo MG, Enejosa JV, et al. ABT-450, ritonavir, ombitasvir, and dasabuvir achieves 97% and 100% sustained virologic response with or without ribavirin in treatment-experienced patients with HCV genotype 1b infection. Gastroenterology. 2014;147(2):359–65.
6. Feld JJ, Jacobson IM, Hézode C, for the ASTRAL-1 Investigators, et al. Sofosbuvir and velpatasvir for HCV genotype 1, 2, 4, 5, and 6 infection. N Engl J Med. 2015;373(27):2599–607.
7. Rockstroh JK, Nelson M, Katlama C, et al. Efficacy and safety of grazoprevir (MK-5172) and elbasvir (MK-8742) in patients with hepatitis C virus and HIV co-infection (C-EDGE CO-INFECTION): a non-randomised, open-label trial. Lancet HIV. 2015;2(8):e319–27.
8. Zeuzem S, Ghalib R, Reddy KR, et al. Grazoprevir–elbasvir combination therapy for treatment-naive cirrhotic and noncirrhotic patients with chronic HCV genotype 1, 4, or 6 infection: a randomized trial. Ann Intern Med. 2015;163(1):1–13.
9. Roth D, Nelson DR, Bruchfeld A, et al. Grazoprevir plus elbasvir in treatment-naive and treatment-experienced patients with hepatitis C virus genotype 1 infection and stage 4–5 chronic kidney disease (the C-SURFER study): a combination phase 3 study. Lancet. 2015;386(10003):1537–45.
10. Dore GJ, Altice F, Litwin AH, et al. Elbasvir–grazoprevir to treat hepatitis C virus in persons receiving opioid agonist therapy: a randomized trial. Grazoprevir and elbasvir plus ribavirin for chronic HCV genotype-1 infection after failure of combination therapy containing a direct-acting antiviral agent. Ann Intern Med. 2016;65(9):625–34.
11. Lawitz E, Gane E, Pearlman B, et al. 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. 2015;385(9973):1075–86.
12. Sulkowski M, Hezode C, Gerstoft J, et al. 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. 2015;385(9973):1087–97.
13. Coburn CA, Meinke PT, Chang W, et al. Discovery of MK-8742: an HCV NS5A inhibitor with broad genotype activity. ChemMedChem. 2013;8(12):1930–40.
14. Summa V, Ludmerer SW, McCauley JA, et al. MK-5172, a selective inhibitor of hepatitis C virus NS3/4a protease with broad activity across genotypes and resistant variants. Antimicrob Agents Chemother. 2012;56(8):4161–7.
15. Kwo P, Gane E, Peng C-Y, et al. Effectiveness of elbasvir and grazoprevir combination, with or without ribavirin, for treatment-experienced patients with chronic hepatitis C infection. Gastroenterology. 2017;152(1):164–75.
16. Zepatier (elbasvir and grazoprevir) (package insert). Merck & Co., Inc.: Whitehouse Station, 2016.
17. European Medicines Agency. Zepatier (elbasvir/grazoprevir): EPAR summary for the public. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Summary_for_the_public/human/004126/WC500211238.pdf. Accessed 27 Mar 2017.
18. Health Canada. Zepatier. http://www.hc-sc.gc.ca/dhp-mps/prodpharma/sbd-smd/drug-med/sbd-smd-2016-zepatier-185866-eng.php. Accessed 27 March 2017.
19. Sperl J, Horvath G, Halota W, et al. Efficacy and safety of elbasvir/grazoprevir and sofosbuvir/pegylated interferon/ribavirin: a phase III randomized controlled trial. J Hepatol. 2016;65(6):1112–9.
20. Kumada H, Suzuki Y, Karino Y, et al. The combination of elbasvir and grazoprevir for the treatment of chronic HCV infection in Japanese patients: a randomized phase II/III study. J Gastroenterol. 2017;52(4):520–33.
21. Hezode C, Colombo M, Spengler U, et al. C-EDGE IBLD: efficacy and safety of elbasvir/grazoprevir in subjects with chronic hepatitis C virus infection and inherited blood disorders. J Hepatol. 2016;58:S342.
22. Afdhal N, Zeuzem S, Kwo P, for the ION-1 Investigators, et al. Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection. N Engl J Med. 2014;370(20):1889–98.
23. Vierling JM, Kugelmas M, Lawitz E, et al. Efficacy of an eight-week regimen of grazoprevir plus elbasvir with and without ribavirin in treatment-naive, noncirrhotic HCV genotype 1B infection. J Hepatol. 2015;62(suppl 2):S618 (abstract P0769).
24. Harvoni (ledipasvir and sofosbuvir) package insert. Foster City: Gilead Sciences; 2016.
25. European Medicines Agency. Harvoni (ledipasvir/sofosbuvir) (summary of product characteristics). http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/003850/WC500177995.pdf. Accessed 27 Mar 2017.
26. Dusheiko GM, Manns MP, Vierling JM, et al. Safety and tolerability of grazoprevir/elbasvir in patients with chronic hepatitis C: integrated analysis of phase 2–3 trials. Hepatology. 2015;62(suppl 1):562A (abstract 712).
27. Hernandez D, Yu F, Huang X, et al. Impact of pre-existing NS5A-L31 or -Y93H minor variants on response rates in patients infected with HCV genotype-1b treated with daclatasvir/asunaprevir. Adv Ther. 2016;33(7):1169–79.
28. Kao J-H, Lee Y-J, Heo J, et al. All-oral daclatasvir plus asunaprevir for chronic hepatitis C virus (HCV) genotype 1b infection: a sub-analysis in Asian patients from the HALLMARK DUAL study. Liver Int. 2016;36(10):1433–41.