New Findings Support Zepatier in Chronic Hepatitis C Patients

Results from multiple analyses at The Liver Meeting provided additional evidence supporting the use of elbasvir and grazoprevir (Zepatier) in patients with chronic hepatitis C (HCV) genotype (GT) 1- or GT4.

This includes HCV-positive individuals who received opioid agonist therapy (OAT), are infected with chronic HCV GT1b, use proton pump inhibitors (PPIs), or have moderate kidney disease, according to a Merck press release.

Zepatier is a fixed-dose combination drug that consists of an HCV NS5A inhibitor and an HCV NS3/4A protease inhibitor. In the United States, the drug is indicated with or without ribavirin (RBV) for the treatment of adults with HCV GT1 or 4 infection.

The CO-STAR 3 Year Follow-Up (3YFU) Trial was an observational cohort study that evaluated chronic HCV reinjection and injecting risk behaviors in patients treated with Zepatier during the C-EDGE CO-STAR study. Interim results presented were from the ongoing 3YFU study.

C-EDGE CO-STAR is a phase 3 clinical trial of patients with chronic HCV GT1, GT4 and/or GT6 who are on OAT — methadone and buprenorphine. Patients who are actively using drugs with high abuse potential were not excluded from the study.

Median time from end of treatment (EOT) in the C-EDGE CO-STAR study to the first visit in the 3YFU study was 330 days. Of the 199 3YFU participants, 108 reported any drug use of non-injecting or injecting drugs in the past 6 months. Forty of whom reported injection drug use in the past month.

Since 2 individuals tested positive for evidence of HCV at the first visit in the 3YFU study, it suggested that despite ongoing drug use, chronic HCV reinfections were uncommon in patients on OAT in the first year following treatment with Zepatier.

The retrospective integrated analysis of data from eleven phase 2 and 3 trials in the clinical development program for Zepatier evaluated the efficacy in patients with GT1b. Involved in the analysis were 1070 chronic HCV GT1b patients who received Zepatier for 12 weeks.

This included treatment naive patients or those who had prior experience with peginterferon alfa/interferon and RBV; those with or without an NS3/4A protease inhibitor; those compensated cirrhotic or non-cirrhotic; and patients with or without HIV-1 co-infection.

The results of the analysis showed that 12 weeks after completing treatment, 97% of patients achieved sustained virologic response (SVR12). For those who did not achieve SVR12, 15 were virologic failures and 15 were lost to follow-up.

Regardless of patient characteristics, rates of SVR12 were consistently high. This included 97% with prior treatment experience, 99% with a presence of compensated cirrhosis, and 94% with HIV-1 co-infection.

Three percent of patients who received Zepatier experienced serious adverse events and 2.9% received placebo.

The post-hoc analysis of HCV GT1 and GT4 patients in 6 studies in the phase 3 clinical program for Zepatier assessed SVR12 in patients who self-reported concomitant use of PPIs. According to the press release, pharmacokinetic interactions that led to the reduction in drug concentrations have previously been reported for some HCV NS5A inhibitors when given concomitantly with PPIs.

Overall, the results of the post-hoc analysis showed that 12% of patients who received Zepatier reported baseline use of PPIs. Of those patients, 96% achieved SVR12 compared to 97% without PPI use. The results suggest that PPI use was not a predictive factor for achieving SVR12.

The abstract received Presidential Poster of Distinction recognition at The Liver Meeting 2016, the press release stated.

The pooled dataset analysis in patients with moderate kidney disease evaluated the impact of Zepatier on renal function, which included patients with chronic kidney disease (CKD) stage 3 (estimated glomerular filtration rate [eGFR] less than 60 and greater than or equal to 30 mL/min/1.73m²).

The analysis looked at 32 patients with stage 3 CKD and 1657 patients with eGFR greater than or equal to 60 mL/min/1.73m₂ who were treated with Zepatier, with or without RBV for 8 (n=91, 5%), 12 (n=1238, 73%), 16 (n=211, 12%), or 18 (n=149, 9%) weeks.

Results of the analysis found that at the end of treatment, 38% of the patients saw improvement in kidney function while 63% remained stable.

“Work remains to be done in the community’s efforts to reduce the global burden of chronic hepatitis C, and Merck is committed to pursuing this goal,” said Eliav Barr, senior VP, global clinical development, infectious diseases and vaccines, Merck Research Laboratories. “Our clinical development program continues to yield meaningful evidence for Zepatier in specific patient populations.”