The safety and efficacy of elbasvir and grazoprevir in participants with hepatitis C virus genotype 1b infection
- 916 Downloads
Genotype 1b (GT1b) is the most common subtype of the hepatitis C virus (HCV). We present an integrated analysis of 1070 participants with HCV GT1b infection from 30 countries who received elbasvir/grazoprevir for 12 weeks.
This is a retrospective analysis of data from participants with chronic HCV GT1b infection enrolled in 11 phase II/III clinical trials. All participants received elbasvir 50 mg plus grazoprevir 100 mg once daily for 12 weeks. The primary end point of all studies was sustained virologic response 12 weeks after completion of therapy (SVR12, HCV RNA < 15 IU/ml).
SVR12 was 97.2% (1040/1070). Of the 30 participants who failed to attain SVR12, 15 relapsed and 15 had nonvirologic failure. Among participant subgroups, SVR12 was high in those with compensated cirrhosis (188/189, 99.5%), HIV co-infection (51/54, 94.4%), and baseline viral load > 800,000 IU/ml (705/728, 96.8%). Resistance-associated substitutions (RASs) at NS5A positions 28, 30, 31, or 93 were present in 21.6% of participants at baseline. SVR12 was 99.6% (820/823) in participants without baseline NS5A RASs and 94.7% (215/227) in those with baseline NS5A RASs. Serious adverse events occurred in 3.2% (34/1070) of participants, nine of which occurred after study medication was completed.
Elbasvir/grazoprevir for 12 weeks represents an effective treatment option for participants with HCV GT1b infection. SVR12 was high in all participant subgroups, including those with compensated cirrhosis, HIV co-infection, and high baseline viral load.
The trials discussed in this paper were registered with Clinicaltrial.gov as the following: NCT02092350 (C-SURFER), NCT02105662 (C-EDGE Co-Infection), NCT02105467 (C-EDGE treatment-naive), NCT02105701 (C-EDGE treatment-experienced), NCT01717326 (C-WORTHy), NCT02251990 (C-CORAL), NCT02105688 (C-EDGE COSTAR), NCT02252016 (C-EDGE IBLD), NCT02115321 (C-SALT), NCT02203149 (Japan phase 2/3 study), NCT02358044 (C-EDGE Head-2-Head).
KeywordsHepatitis Retrospective Therapy
The authors extend their gratitude to the participants, their families, investigators and site personnel who participated in this study. The studies included in this analysis were funded by Merck & Co., Inc. Medical writing and editorial assistance was provided by Tim Ibbotson, PhD, of ApotheCom and funded by Merck & Co., Inc., Kenilworth, NJ, USA.
These studies were funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
Compliance with ethical standards
Conflict of interest
Stefan Zeuzem has served a consultant for AbbVie, BMS, Gilead, Janssen, and Merck/MSD. Lawrence Serfaty has received personal fees from MSD, Gilead, Janssen, Bristol-Myers Squibb, and AbbVie. John Vierling has received grants or other payments from AbbVie, Bristol-Myers Squibb, Conatus, Genentech, Genentech, Gilead, Gilead, Merck, Novartis, and Sundise. Wendy Cheng has received personal fees from Merck for participation on a Medical Education Expert Input Forum. Jacob George has received personal fees from MSD, AbbVie, Gilead, Pharmaxis, and Bristol-Myers Squibb. Jan Sperl has received research grants from Gilead and Janssen-Cilag and personal fees for speaker/advisor roles with Gilead, Janssen-Cilag, Merck, and AbbVie. Simone Strasser has received personal fees from MSD/Merck, Gilead Sciences, AbbVie, Bristol-Myers Squibb, and Janssen. Hiromitsu Kumada has received grants from MSD KK during the conduct of the study and personal fees from MSD KK, GSK, Tanabe-Mitsubishi, Bristol-Myers Squibb, and Janssen, and has a patent SRL licensed. Peggy Hwang, Michael Robertson, Janice Wahl, Eliav Barr, Rohit Talwani, and Heather Platt are employees of and hold stock in Merck & Co., Inc.
- 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.CrossRefPubMedGoogle Scholar
- 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.CrossRefGoogle Scholar
- 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.CrossRefPubMedGoogle Scholar
- 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.CrossRefPubMedGoogle Scholar
- 16.Zepatier (elbasvir and grazoprevir) (package insert). Merck & Co., Inc.: Whitehouse Station, 2016.Google Scholar
- 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.
- 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.Google Scholar
- 24.Harvoni (ledipasvir and sofosbuvir) package insert. Foster City: Gilead Sciences; 2016.Google Scholar
- 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).Google Scholar