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