Real-World Study Shows ZEPATIER® (Elbasvir and Grazoprevir) Resulted in High Rates of Sustained Virologic Response in Patients with Chronic Hepatitis C Infection who have Chronic Kidney Disease
Observational Analysis Evaluated Patients in U.S. Veterans Affairs System
KENILWORTH, N.J., October 21, 2017 – 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) genotype (GT) 1 or 4 infection who have chronic kidney disease (CKD) and were treated with ZEPATIER® (elbasvir and grazoprevir) in the U.S. Department of Veterans Affairs (VA) healthcare system. Among patients who completed therapy, the analysis showed 95.6 percent (714/747) of patients with severe CKD (stages 4-5, defined as estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2) and 97.1 percent (758/781) of patients with moderate CKD (stage 3, defined as eGFR 30-59 mL/min/1.73 m2) achieved sustained virologic response (SVR), defined as HCV RNA below the limit of quantification at least 10-12 weeks after the end of treatment. For patients with missing HCV RNA data after at least 10-12 weeks after treatment completion, analyses were conducted on a post-hoc basis using the last HCV RNA data available after week 4 after therapy completion. The response rates in the real-world setting of the VA further supplement findings from controlled clinical studies of ZEPATIER.
Observational Analysis Evaluated Patients in U.S. Veterans Affairs System
KENILWORTH, N.J., October 21, 2017 – 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) genotype (GT) 1 or 4 infection who have chronic kidney disease (CKD) and were treated with ZEPATIER® (elbasvir and grazoprevir) in the U.S. Department of Veterans Affairs (VA) healthcare system. Among patients who completed therapy, the analysis showed 95.6 percent (714/747) of patients with severe CKD (stages 4-5, defined as estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2) and 97.1 percent (758/781) of patients with moderate CKD (stage 3, defined as eGFR 30-59 mL/min/1.73 m2) achieved sustained virologic response (SVR), defined as HCV RNA below the limit of quantification at least 10-12 weeks after the end of treatment. For patients with missing HCV RNA data after at least 10-12 weeks after treatment completion, analyses were conducted on a post-hoc basis using the last HCV RNA data available after week 4 after therapy completion. The response rates in the real-world setting of the VA further supplement findings from controlled clinical studies of ZEPATIER.
These findings will be presented today at The Liver Meeting® 2017 taking place in Washington, D.C.
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 at 12 weeks after the cessation of treatment (SVR12).
“These results demonstrate that U.S. veterans with chronic hepatitis C infection can achieve virologic cure in a real-world setting despite having co-morbid chronic kidney disease,” said Jennifer Kramer, investigator, Center for Innovations in Quality, Effectiveness and Safety at the Michael E. DeBakey VA Medical Center, Houston, Texas, and assistant professor of medicine, department of medicine, Baylor College of Medicine. “There is an ongoing need for an increased focus on screening and treating veterans and others who are disproportionately impacted by this disease.”
The retrospective observational analysis included 5,845 patients with chronic HCV infection who received ZEPATIER (elbasvir and grazoprevir) between February 1 and December 31, 2016. Patients were identified from the VA Corporate Data Warehouse, a national repository of VA electronic medical records. Presence of chronic kidney disease was measured via eGFR, per the National Kidney Foundation’s Modification of Diet in Renal Disease equation. Of 4,693 patients evaluated in the per protocol population, 16.6 percent (781/4693) had CKD stage 3 and 15.9 percent (747/4693) had CKD stages 4 or 5. Please see additional information below about the design, methodology and limitations of this observational analysis.
“Researching the needs of veterans is part of our collective responsibility to those who have served our country,” said Susan Shiff, senior vice president, Center for Observational and Real-World Evidence, Merck. “The robust nature of VA medical data enables us to study the effectiveness of ZEPATIER for the treatment of chronic hepatitis C infection in people with kidney disease and other comorbid conditions in that real-world setting.”
Adverse event data were not collected as part of this real-world data analysis.
Most patients with chronic kidney disease in the analysis were male (96.9%, 1481/1528); African American (67.5%, 1031/1528) and either had GT1a infection (52.2%, 798/1528) or GT1b infection (42.1%, 644/1528). The mean age for patients in the study with chronic kidney disease was 64.9 years. Comorbid conditions as defined by ICD-9/10 codes in the VA database included depression (58.5%, 894/1528), diabetes (69.2%, 1057/1528), compensated cirrhosis (18.6%, 284/1528), and HIV (5.0%, 76/1528). In the study, 19.9 percent of patients (304/1528) were coded as having decompensated cirrhosis; ZEPATIER is not for use in patients with moderate or severe hepatic impairment (Child Pugh B or C). See Selected Safety Information below for more information.
Study Methodology
The database included patients ages 18 and older with chronic HCV infection who initiated treatment with ZEPATIER between February 1, 2016, and December 31, 2016, and had at least one inpatient or outpatient visit within a year prior to treatment (n=5845). The study excluded patients without ≥2 eGFR values at least 90 days apart or on-treatment HCV RNA data, patients who did not receive 12-16 weeks of treatment with ZEPATIER and patients who received RBV >1 month after initiating treatment (n=1152).
SVR was defined in the protocol for these analyses as HCV RNA below the limit of quantification at least 10-12 weeks after the end of treatment. For patients with missing HCV RNA data at week 10-12 after treatment completion, analyses were conducted on a post-hoc basis using HCV RNA data captured starting from week 4 after therapy completion. SVR data at least 12 weeks after completion of therapy was available for 81.9% of the analysis 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-9/10 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. Additionally, some laboratory data including data on the presence of baseline NS5A resistance associated substitutions was not available at the time of this analysis.
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 at 12 weeks after the cessation of treatment (SVR12).
“These results demonstrate that U.S. veterans with chronic hepatitis C infection can achieve virologic cure in a real-world setting despite having co-morbid chronic kidney disease,” said Jennifer Kramer, investigator, Center for Innovations in Quality, Effectiveness and Safety at the Michael E. DeBakey VA Medical Center, Houston, Texas, and assistant professor of medicine, department of medicine, Baylor College of Medicine. “There is an ongoing need for an increased focus on screening and treating veterans and others who are disproportionately impacted by this disease.”
The retrospective observational analysis included 5,845 patients with chronic HCV infection who received ZEPATIER (elbasvir and grazoprevir) between February 1 and December 31, 2016. Patients were identified from the VA Corporate Data Warehouse, a national repository of VA electronic medical records. Presence of chronic kidney disease was measured via eGFR, per the National Kidney Foundation’s Modification of Diet in Renal Disease equation. Of 4,693 patients evaluated in the per protocol population, 16.6 percent (781/4693) had CKD stage 3 and 15.9 percent (747/4693) had CKD stages 4 or 5. Please see additional information below about the design, methodology and limitations of this observational analysis.
“Researching the needs of veterans is part of our collective responsibility to those who have served our country,” said Susan Shiff, senior vice president, Center for Observational and Real-World Evidence, Merck. “The robust nature of VA medical data enables us to study the effectiveness of ZEPATIER for the treatment of chronic hepatitis C infection in people with kidney disease and other comorbid conditions in that real-world setting.”
Adverse event data were not collected as part of this real-world data analysis.
Most patients with chronic kidney disease in the analysis were male (96.9%, 1481/1528); African American (67.5%, 1031/1528) and either had GT1a infection (52.2%, 798/1528) or GT1b infection (42.1%, 644/1528). The mean age for patients in the study with chronic kidney disease was 64.9 years. Comorbid conditions as defined by ICD-9/10 codes in the VA database included depression (58.5%, 894/1528), diabetes (69.2%, 1057/1528), compensated cirrhosis (18.6%, 284/1528), and HIV (5.0%, 76/1528). In the study, 19.9 percent of patients (304/1528) were coded as having decompensated cirrhosis; ZEPATIER is not for use in patients with moderate or severe hepatic impairment (Child Pugh B or C). See Selected Safety Information below for more information.
Study Methodology
The database included patients ages 18 and older with chronic HCV infection who initiated treatment with ZEPATIER between February 1, 2016, and December 31, 2016, and had at least one inpatient or outpatient visit within a year prior to treatment (n=5845). The study excluded patients without ≥2 eGFR values at least 90 days apart or on-treatment HCV RNA data, patients who did not receive 12-16 weeks of treatment with ZEPATIER and patients who received RBV >1 month after initiating treatment (n=1152).
SVR was defined in the protocol for these analyses as HCV RNA below the limit of quantification at least 10-12 weeks after the end of treatment. For patients with missing HCV RNA data at week 10-12 after treatment completion, analyses were conducted on a post-hoc basis using HCV RNA data captured starting from week 4 after therapy completion. SVR data at least 12 weeks after completion of therapy was available for 81.9% of the analysis 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-9/10 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. Additionally, some laboratory data including data on the presence of baseline NS5A resistance associated substitutions was not available at the time of this analysis.
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