Journal of Gastroenterology

, Volume 53, Issue 5, pp 679–688 | Cite as

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

  • Stefan Zeuzem
  • Lawrence Serfaty
  • John Vierling
  • Wendy Cheng
  • Jacob George
  • Jan Sperl
  • Simone Strasser
  • Hiromitsu Kumada
  • Peggy Hwang
  • Michael Robertson
  • Janice Wahl
  • Eliav Barr
  • Rohit Talwani
  • Heather Platt
Original Article—Liver, Pancreas, and Biliary Tract

Abstract

Background

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.

Methods

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).

Results

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.

Conclusions

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.

ClinicalTrials.gov identifiers

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).

Keywords

Hepatitis Retrospective Therapy 

Notes

Acknowledgements

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.

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.

Supplementary material

535_2018_1429_MOESM1_ESM.pdf (149 kb)
Supplementary material 1 (PDF 148 kb)
535_2018_1429_MOESM2_ESM.pdf (170 kb)
Supplementary material 2 (PDF 169 kb)
535_2018_1429_MOESM3_ESM.pdf (98 kb)
Supplementary material 3 (PDF 97 kb)
535_2018_1429_MOESM4_ESM.pdf (82 kb)
Supplementary material 4 (PDF 81 kb)

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Copyright information

© Japanese Society of Gastroenterology 2018

Authors and Affiliations

  • Stefan Zeuzem
    • 1
  • Lawrence Serfaty
    • 2
  • John Vierling
    • 3
  • Wendy Cheng
    • 4
  • Jacob George
    • 5
  • Jan Sperl
    • 6
  • Simone Strasser
    • 7
  • Hiromitsu Kumada
    • 8
  • Peggy Hwang
    • 9
  • Michael Robertson
    • 9
  • Janice Wahl
    • 9
  • Eliav Barr
    • 9
  • Rohit Talwani
    • 9
  • Heather Platt
    • 9
  1. 1.Goethe University HospitalFrankfurtGermany
  2. 2.Service d’Hépatologie, Hôpital Saint-AntoineUniversité Pierre and Marie CurieParisFrance
  3. 3.Baylor College of Medicine, Advanced Liver TherapiesHoustonUSA
  4. 4.Department of Gastroenterology and HepatologyRoyal Perth HospitalPerthAustralia
  5. 5.Storr Liver Centre, Westmead Institute for Medical ResearchWestmead Hospital and University of SydneySydneyAustralia
  6. 6.Institute for Clinical and Experimental Medicine (IKEM)PragueCzech Republic
  7. 7.AW Morrow Gastroenterology and Liver CentreRoyal Prince Alfred HospitalSydneyAustralia
  8. 8.Department of HepatologyToranomon HospitalTokyoJapan
  9. 9.Merck & Co., Inc.KenilworthUSA

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