Efficacy and safety of elbasvir/grazoprevir for 12 weeks in people with hepatitis C virus infection aged 35 years or younger compared with older people: a retrospective integrated analysis

Abstract

Background: In the United States, the number of new cases of hepatitis C virus infection has risen in recent years, driven largely by transmission among young white adults in their 20s and 30s. Herein, we report an integrated analysis of participants with hepatitis C virus infection aged ≤35 years from 12 phase II/III clinical trials of elbasvir/grazoprevir.

Methods: Treatment-naive and -experienced adults with hepatitis C virus genotype 1 or 4 infection received elbasvir (50 mg/day)/grazoprevir (100 mg/day) for 12 weeks without ribavirin. Analyses were stratified according to participant age (≤35 years vs >35 years). The primary endpoint was sustained virologic response (hepatitis C virus RNA < lower limit of quantitation at 12 weeks after completion of therapy).

Results: Sustained virologic response was achieved by 98.9% (271/274) of participants aged ≤35 years and by 96.9% (2093/2160) aged >35 years. Three participants aged ≤35 years with genotype 1b infection relapsed. Eight participants with genotype 1a infection and baseline non-structural protein 5 A resistance-associated substitutions achieved sustained virologic response. Similarly, all 85 participants aged ≤35 years with genotype 1a infection and no baseline non-structural protein 5 A resistance-associated substitutions achieved sustained virologic response. Safety was favorable, with the incidence of drug-related adverse events similar in younger and older participants (30.1% vs 30.6%). One participant (0.4%) aged ≤35 years and 15 participants (0.7%) aged >35 years discontinued treatment owing to adverse events.

Conclusions: Elbasvir/grazoprevir for 12 weeks was safe and highly effective in participants aged ≤35 years with hepatitis C virus genotype 1 or 4 infection.

Keywords:

• Hepatitis C
• chronic
• young adult
• drug therapy
• clinical trial

Transparency

Declaration of funding

This study was supported by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co. Inc., Kenilworth, NJ, USA.

Declaration of financial/other relationships

T.A. has disclosed that he has received grants from Merck Sharp & Dohme Corp., a subsidiary of Merck & Co. Inc., Kenilworth, NJ, USA, AbbVie, Gilead, Janssen and Roche; and received personal fees as a clinical investigator, speaker and consultant for MSD, AbbVie, Gilead, Janssen and Roche. S.Z. has disclosed that he has received personal fees as a consultant and lecture honoraria from AbbVie, Gilead, Janssen and MSD. N.R. has disclosed that she has received personal advisory fees from AbbVie, Gilead and MSD. P.H., M.N.R. and B.A.H. have disclosed that they are employees of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co. Inc., Kenilworth, NJ, USA, and own stock in Merck & Co. Inc., Kenilworth, NJ, USA. J.L. and R.T. have disclosed that they were employees of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co. Inc., Kenilworth, NJ, USA, at the time of the trials and data analyses. CMRO peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

Conception, design or planning of the study: T.A., R.T., M.N.R., B.A.H.; acquisition of the data: T.A., S.Z., N.R.; analysis of the data: P.H., J.L.; interpretation of the results: all authors; drafting of the manuscript: T.A., R.T., M.N.R.; critically reviewing or revising the manuscript for important intellectual content: all authors; final approval of the version to be published: all authors.

Acknowledgements

We extend our gratitude to the participants, their families, investigators and site personnel who participated in these studies. Medical writing and editorial assistance were provided by Tim Ibbotson PhD of ApotheCom, Yardley, PA, and were funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co. Inc., Kenilworth, NJ, USA.

Data availability statement

The Merck Sharp & Dohme Corp. data sharing policy, including restrictions, is available at http://engagezone.msd.com/ds_documentation.php. Requests for access to the clinical study data can be submitted through the EngageZone site or via email to [email protected].