Treatment options for patients infected with the hepatitis C virus (HCV) have evolved substantially since the first Direct-Acting Antiviral (DAA) therapies were introduced in 2011. The pace of change has recently accelerated, with several new drugs offering different mechanisms of action introduced in the previous six months and additional approvals anticipated over the next few years. As a result, the prognosis for millions of patients living with chronic hepatitis C has dramatically improved, with new therapy options that are all-oral, better tolerated, of a shorter treatment duration and curative in many cases. Healthcare efforts are transitioning focus from stabilizing and maintaining the health status of patients with hepatitis C to curing them.
Background: Prevalence and Disease Progression
Hepatitis C is a liver disease caused by blood-borne infection with HCV and is the most common chronic blood-borne infection in the U.S. The estimated prevalence of chronic HCV infection is 3.2 million persons in the U.S.1 However, the true prevalence may be as high as 5.2 million persons when including high risk groups such as the institutionalized, incarcerated and homeless populations.2 Infection is most prevalent among those born between 1945–1965, the majority of whom were likely infected during the 1970s and 1980s when rates were highest.3
There are six major HCV genotypes, or genetic variations of the virus (genotypes 1 to 6), as well as subtypes thereof. In the U.S., genotype 1 is the most prevalent and accounts for approximately 75% of HCV cases. Genotypes 2 and 3 account for most of the remaining HCV cases (20% to 25%).4 For every 100 persons infected with HCV, approximately3:
- 75–85 will go on to develop chronic infection
- 60–70 will go on to develop chronic liver disease
- 5–20 will go on to develop cirrhosis over a period of 20–30 years
- 1–5 will die from the consequences of chronic infection (liver cancer or cirrhosis)
Of note, deaths attributed to hepatitis C surpassed those due to HIV/AIDS for the first time in 2007.3
Most patients with chronic HCV infection are asymptomatic. However, many, as noted above, have chronic liver disease, which can range from mild to severe, including cirrhosis and liver cancer. Chronic liver disease in HCV-infected patients is usually insidious, progressing slowly without any signs or symptoms for several decades. In fact, HCV infection is often not recognized until asymptomatic patients are identified as HCV-positive when screened for blood donation or when elevated alanine aminotransferase (ALT, a liver enzyme) levels are detected by routine examination. 3
Beyond liver complications, chronic HCV infection may lead to extra-hepatic manifestations, including hematological malignancies, dermatological diseases, kidney disease and neurocognitive disorders. Extrahepatic manifestations, such as debilitating fatigue, can have a negative impact on the quality of life of patients. Chronic HCV infection is also associated with an increased incidence of non-Hodgkin’s lymphoma. 3
Cost of Disease
A number of studies have examined the cost burden associated with HCV. In one retrospective data analysis by a large managed care organization, patients diagnosed with HCV had annual all-cause medical costs that were almost twice as high as those enrollees without a diagnosis of HCV. Healthcare costs increased dramatically with advanced liver disease.
Specifically, incremental mean per patient per year (PPPY) costs for all HCV patients relative to comparison patients were $9,681 PPPY. Incremental PPPY costs were $5,870 and $5,330 for HCV patients without liver disease and with compensated cirrhosis, respectively. Incremental PPPY costs for patients with advanced liver disease were $27,845 for decompensated cirrhosis, $43,671 for hepatocellular cancer (HCC) and $93,609 for transplant. 5
The goal of treatment is to prevent virus transmission, complications and death from HCV. Because of the slow and often asymptomatic evolution of chronic HCV infection, surrogate virologic markers are used to measure treatment outcome. The most important outcome measure is the sustained virologic response (SVR), defined as the absence of HCV RNA at 12 or 24 weeks after therapy discontinuation. Successful treatment of HCV resulting in a SVR, e.g., complete elimination of the HCV, is deemed a virologic ”cure.” Observational studies have shown a correlation between SVR and improvements in clinical outcomes such as all-cause mortality, liver-related mortality, hepatocellular carcinoma and liver transplantation.
Prior to the introduction of the first oral DAA therapies in 2011, HCV treatment was limited to a combination drug regimen of subcutaneously injected pegylated interferon plus oral ribavirin. This standard of care at the time imparted an average SVR of only 44-46%, required weekly injections, came with significant side effects and often required a treatment duration of 48 weeks.
The first wave of oral DAA therapies was approved in 2011 and included Victrelis (boceprevir) and Incivek (telaprevir). The use of either drug in combination with interferon and ribavirin was found to increase the SVR to 70% or more. Despite the improvement in SVR, use of both Victrelis and Incivek was associated with higher rates of adverse events, numerous drug interactions, a continued need for injected interferon and ribavirin, not to mention an increased pill burden.
The marketing of Victrelis and Incivek was discontinued in late 2013, upon the introduction of the second wave of oral DAA therapies, Olysio (simeprevir) and Sovaldi (sofosbuvir). These second generation drugs deliver greater SVR rates (SVR ≥ 90%) with a more favorable side effect profile and lower pill burden. While Olysio requires coadministration with interferon and ribavirin, Solvaldi may be administered with or without these additional two medications depending on the clinical scenario.
In late 2014, the FDA approved two new interferonfree drug regimens, Harvoni and Viekira Pak, for the treatment of genotype 1 disease. Harvoni distinguishes itself from all other genotype 1 options by offering a lower potential for meaningful drug interactions, a once-daily, single-tablet regimen, and the availability of an abbreviated 8-week course for selected patients with specific clinical attributes.
Healthcare professionals rely upon information from the FDA and drug manufacturers as well as the AASLD and IDSA Guidelines: Recommendations for Testing, Managing, and Treating Hepatitis C, as a guide to aid in drug selection, selection of concomitant therapies, if any, and treatment duration. These guidelines are updated as new data becomes available and incorporate newly approved drugs as they are introduced into the marketplace. 6
The AASLD-IDSA guidelines currently describe Viekira Pak, Harvoni and Sovaldi coadministered with Olysio as having comparable efficacy and safety profiles for the treatment of the general genotype 1 patient population and recommend any of these regimens for the initial treatment of HCV infection or retreatment of patients who failed prior therapy. 6
Based on the available data, the guidelines recommend Harvoni as the preferred regimen in several genotype 1 subpopulations, the most prevalent genotype. Harvoni is also the only agent that has been studied in patients who have failed prior DAA therapy, and the treatment guidelines also support the use of Harvoni in the subset of decompensated patients. Compared to Viekira Pak and other regimens, Harvoni is associated with less potential for drug interactions and it is the only once daily, single tablet regimen currently available. For patients with the less prevalent genotypes 2, 3 and 4, Sovaldi is the only FDA approved regimen.6
Formulary Status and Place in Therapy
Serve You recognizes the complexity of HCV pharmacotherapy as well as the unique needs of patients with hepatitis C, including the need for therapeutic options and individualized treatment plans based on clinical characteristics, disease severity, treatment guidelines, prior therapies and other attributes. On the Serve You Preferred Drug List (PDL), Harvoni and Sovaldi are the current preferred options for the treatment of HCV.
For plans using the Serve You 2-Tier or 3-Tier PDL, Harvoni and Sovaldi reside on Tier 2 of the PDL.
For plans using the Serve You 4-Tier PDL, all drugs—Harvoni, Sovaldi, Olysio and Viekira Pak— reside on Tier 4.
Harvoni, Solvaldi, Olysio and Viekira Pak are all dispensed by the Serve You DirectRxSM Pharmacy and are included in the Serve You Specialty Drug Management Program and Clinical Prior Authorization Program. The Serve You DirectRx Specialty Pharmacy team (of clinical pharmacists and nurses) provides comprehensive and individualized clinical care management to patients receiving specialty drugs, assists with coordination of benefits and patient assistance programs, partners with case or disease management vendors and monitors for adherence to help patients get the maximum benefit from their specialty drug.
Serve You Specialty Drug Management includes comprehensive tactics to manage specialty drug trend, ensure clinically appropriate and cost-effective utilization, and improve outcomes.
- Denniston MM, Jiles RB, Drobeniuc J, et al. Chronic hepatitis C virus infection in the United States, National Health and Nutrition Examination Survey 2003 to 2010. Ann Intern Med. 2014;160(5):293-300.
- Chak, E., Talal, A. H., Sherman, K. E., Schiff, E. R. et al. Hepatitis C virus infection in USA: an estimate of true prevalence. Liver International. 2011;31:1090–1101.
- Messina, J. P., Humphreys, I., Flaxman, A., et al. Global distribution and prevalence of hepatitis C virus genotypes. Hepatology, 2015;61: 77–87.
- McAdam-Marx C, McGarry L, Hane C, et al. All-Cause and Incremental Per Patient Per Year Cost Associated with Chronic Hepatitis C Virus and Associated Liver Complications in the United States: A Managed Care Perspective. J Manag Care Pharm. 2011;17(7):531-46.