Efficacy
Renal impairment
In chronic HCV GT1 infection:
A powerful cure* for patients with renal impairment, including those on hemodialysis
* Cure = sustained virologic response, defined as HCV ribonucleic acid (RNA) less than lower limit of quantification (<LLOQ) at 12 weeks after completion of therapy (SVR12).1 SVR12 was the primary end point in all studies.
ZEPATIER is indicated for the treatment of chronic hepatitis C virus (HCV) genotype (GT) 1 or 4 infection in adults. ZEPATIER is indicated for use with ribavirin (RBV) in certain patient populations.

Study design
Randomized, double-blind, placebo-controlled study in patients with HCV GT1 infection, with or without cirrhosis, with CKD stage 4 (eGFR 15–29 mL/min/1.73 m2) or stage 5 (eGFR <15 mL/min/1.73 m2), including patients on hemodialysis, who were TN or who failed prior therapy with IFN or pegIFN ± RBV. Patients were randomized in a 1:1 ratio to the following treatment groups: ZEPATIER for 12 weeks (immediate-treatment group, n=111) or placebo for 12 weeks followed by open-label treatment with ZEPATIER for 12 weeks (deferred-treatment group, n=113). In addition, 11 patients received open-label ZEPATIER for 12 weeks (intensive pharmacokinetic [PK] group). Among patients in the immediate-treatment and intensive PK groups, 45% were Black or African American, 6% had cirrhosis, 52% had GT1a infection, and 48% had GT1b infection. SVR12 was assessed in the pooled immediate-treatment group and the intensive PK group (n=122).
- No patients experienced on-treatment virologic failure, and 1 patient experienced treatment relapse.
- Consistently high cure* rates were seen in patients receiving hemodialysis (93%, 86/92) and those not receiving hemodialysis (97%, 29/30).
- More than one-third of the patients receiving ZEPATIER in C-SURFER had comorbid diabetes.2
99% (115/116) of patients included in the prespecified primary analysis population achieved SVR12
- This population excluded patients not receiving at least 1 dose of study treatment and those with missing data due to death or early study discontinuation for reasons unrelated to treatment response (n=6).
ZEPATIER is predominantly eliminated through the liver (not the kidneys), providing a treatment option for chronic HCV–infected patients with any degree of renal impairment.
Definitions
CKD = chronic kidney disease
eGFR = estimated glomerular filtration rate
IFN = interferon
pegIFN = peginterferon alfa
RBV = ribavirin
TN = treatment-naïve
References
1. AASLD-IDSA. Recommendations for testing, managing, and treating hepatitis C. http://www.hcvguidelines.org. Accessed March 16, 2018.
2. Roth D, Nelson D, 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;386:1537–1545.