Study Evaluated VA Population with High Incidence of Co-Morbidities
April 21, 2017 10:00 AM Eastern Daylight Time
KENILWORTH, N.J.--(BUSINESS WIRE)--Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced the presentation of findings from a retrospective database analysis of patients with chronic hepatitis C virus (HCV) infection who were administered ZEPATIER® in the U.S. Department of Veterans Affairs (VA) healthcare system. For the evaluable population (n=2,436), 95.6 percent of veterans treated with ZEPATIER achieved the primary outcome of sustained virologic response (SVR), defined as undetectable HCV RNA at least twelve weeks after the end of treatment. For patients with no HCV RNA measurements at or after 12 weeks (19% of the study cohort), the analysis used HCV RNA measurements available at least four and less than 12 weeks after the end of treatment. The response rates in the real-world setting of the VA supplement the overall findings from the controlled clinical studies of ZEPATIER. These findings will be presented today in an oral session (abstract #PS-095) at The International Liver Congress™ 2017 being held in Amsterdam, the Netherlands.
In the United States, ZEPATIER is indicated for the treatment of chronic HCV GT1 or GT4 infection in adults. ZEPATIER is indicated for use with ribavirin (RBV) in certain patient populations. The U.S. Prescribing Information for ZEPATIER includes a Boxed Warning about the risk of hepatitis B virus (HBV) reactivation in patients co-infected with HCV and HBV. In controlled clinical studies of ZEPATIER, SVR was the primary endpoint defined as HCV RNA less than lower limit of quantification (LLOQ) at 12 weeks after the cessation of treatment (SVR12).
“U.S. veterans are three times more likely to have chronic hepatitis C compared to the general U.S. population and a high proportion suffer co-morbid conditions that can make treatment challenging,” said Jennifer Kramer, investigator, Michael E. DeBakey VA Medical Center, Houston, Texas, and assistant professor of medicine, department of medicine, Baylor College of Medicine. “This study shows that chronic hepatitis C antiviral treatment can result in a high rate of sustained virologic response in U.S. veterans.”
This retrospective database analysis included patients with chronic HCV treated with ZEPATIER (elbasvir and grazoprevir) in the VA healthcare system between February 1, 2016 and August 1, 2016. Study outcomes include real-world utilization and SVR rates. Please see additional information about the design, methodology and limitations of this observational study below.
After applying study exclusion criteria, 2,436 patients were included in the evaluable population cohort. The mean age of subjects was 63.5 years. The prevalence of co-morbidities as determined by ICD-9 and CPT codes as recorded in the VA database was as follows: cirrhosis (33.2%), diabetes (53.2%), depression (57.2%) and HIV co-infection (3%). Additionally, more than half of the patients had a history of drug (53.9%) or alcohol (60.5%) abuse. The population included 1,988 previously untreated patients and 448 treatment-experienced patients (322 of whom previously received an interferon-based regimen with or without an NS3/4A HCV protease inhibitor, and 126 of whom previously received an interferon-free direct-acting antiviral regimen).
A total of 95.6 percent (2,328/2,436) of patients in the evaluable population achieved SVR following treatment with ZEPATIER. The SVR rates by genotype (GT) were as follows: all GT1, 95.4 percent (2218/2324); GT1a, 93.4 percent (788/844); GT1b, 96.6 percent (1379/1428); and GT4, 96.9 percent (62/64). The SVR rates by baseline viral load (BVL) were as follows: BVL greater than 800,000 IU/ml, 94.7 percent (1497/1580); and BVL less than or equal to 800,000 IU/ml, 97.3 percent (726/746).
The SVR rates by baseline patient characteristics were as follows: male, 95.5 percent (2,245/2,350); female, 96.5 percent (83/86); African American, 95.9 percent (1,342/1,400); Hispanic, 95.1 percent (77/81); White, 95.0 percent (783/824); previously untreated, 96.1 percent (1,910/1,988); treatment-experienced, 93.3 percent (418/448); cirrhosis, 95.5 percent (772/808); without cirrhosis, 95.6 percent (1556/1628); stage 3 chronic kidney disease (CKD) (eGFR 30 to 59 mL/min/1.73m2), 96.7 percent (380/393); stage 4-5 CKD (eGFR less than 30 mL/min/1.73m2), 96.3 percent (392/407); HIV positive, 98.6 percent (73/74); HIV negative, 95.5 percent (2255/2362); history of alcohol abuse, 95.9 percent (1412/1473); no history of alcohol abuse, 95.1 percent (916/963); history of drug abuse, 95.3 percent (1251/1313); no history of drug abuse, 95.9 percent (1077/1123).
Adverse event data were not collected as part of this real-world data analysis.
“Analysis of data from real-world medical settings can provide useful insights to supplement knowledge gained from randomized clinical trials,” said Susan Shiff, senior vice president, center for observational and real-world evidence, Merck. “These data from a real-world VA setting add to the body of evidence on ZEPATIER (elbasvir and grazoprevir) and help deepen scientific understanding of the treatment of this complex disease affecting diverse, sometimes difficult to treat, patient populations.”
Study Methodology
Patients with chronic HCV treated with ZEPATIER from February 1 to August 1, 2016 were identified from the VA Corporate Data Warehouse, a national repository of VA electronic medical records. Inclusion criteria specified initiation of ZEPATIER therapy, at least 18 years of age, positive HCV RNA, and at least one inpatient or outpatient visit within a one-year period prior to treatment initiation (n=2,985). Patients were excluded if they had RBV added greater than one month after treatment initiation (n=23). Patients without SVR data or on-treatment HCV RNA data (n=494), or those treated with ZEPATIER for greater than seventeen weeks (n=32), were excluded as well. The total number of patients in the evaluable population was 2,436.
SVR was assessed based on undetectable HCV RNA at least twelve weeks after the end of treatment. For patients with no HCV RNA measurements at or after 12 weeks, the analysis used HCV RNA measurements available at least four and less than 12 weeks after the end of treatment. SVR was evaluated based on HCV RNA measurement at least 12 weeks post treatment in 81 percent of the study population.
About Real-World Data Analyses and Associated Limitations
Real-world studies analyze data generated outside of randomized clinical trials, such as through analyses of electronic medical records or claims databases, to provide insight into how medicines perform or are used from a clinical and economic viewpoint in real-world clinical settings. Information from real-world analyses alone does not provide sufficient evidence to validate efficacy or safety of a therapeutic regimen and does not provide a substitute for evidence obtained from randomized controlled clinical trials.
This study is subject to certain limitations. The VA population may not be generalizable to the entire U.S. population, due in part to the potential for a differing demographic make-up and/or risk factors. Bias may exist as diagnoses and co-morbidities were identified through ICD-9 and CPT codes. Treatment completion was identified through prescription records which may not reflect adherence. Database analyses are also prone to errors in coding and missing data, including unavailable SVR data at or after the 12-week post-treatment time point. Additionally, some laboratory data including data on the presence of baseline NS5A resistance associated substitutions was not available at the time of this analysis.
About the VA Corporate Data Warehouse (CDW)
The Department of Veterans Affairs Veterans Healthcare Administration (VHA) is supported by one of the largest integrated healthcare information systems in the United States. The VHA's Corporate Data Warehouse (CDW) was developed in 2006 to accommodate the massive amounts of data being generated from more than 20 years of use and to streamline the process of knowledge discovery to application.
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