Viekira Pak (Ombitasvir, Paritaprevir, and Ritonavir Tablets; Dasabuvir Tablets): All-Oral Fixed Combination Approved for Genotype 1 Chronic Hepatitis C Infection.

Approximately 130 million to 170 million individuals worldwide, including 3.2 million Americans, are infected with chronic hepatitis C virus (HCV), making it the most common blood-borne disease.1,2 Chronic HCV infection is a silent epidemic; the disease can remain quiescent for decades before clinically significant symptoms appear.3 The prevalence of HCV and its complications are expected to rise as Americans who are currently living with HCV enter their 50s and 60s.4 Research indicates that by 2015, more than 3 million individuals will have HCV infection that has been present for 20 years or more, which will result in a significant increase in the incidence of advanced liver disease, including cirrhosis, decompensated cirrhosis, and liver cancer.5,6 The Centers for Disease Control and Prevention estimates that for every 100 individuals infected with HCV, 1 to 5 will die from liver cancer or cirrhosis.1 In addition to causing substantial morbidity and mortality, HCV is associated with significant financial consequences.3,7 A 2000 study estimated that between 2010 and 2019, the direct medical expenditures for HCV-related conditions will reach nearly $11 billion, the cost of morbidity from disability related to decompensated cirrhosis and hepatocellular carcinoma would reach approximately $21 billion, and the societal cost of premature mortality for patients aged <65 years will exceed $54 billion (in 1999 US dollars). 7 HCV is currently the only chronic viral infection that is curable with antiviral therapy. The goals of current anti-HCV approaches are to eradicate infection, to avoid complications, and to prevent the spread of HCV to others.8 In the early 1990s, single-agent interferon was the standard of care for patients with HCV infection. Single-agent interferon represented a significant therapeutic advancement, because until then there was no treatment available for HCV infection; however, single-agent interferon offered a sustained virologic response (SVR) rate of less than 10% in patients with HCV genotype 1, the most common HCV subtype.8 Interferon was then used in combination with ribavirin, increasing the SVR rate by another 14% to 22%. 8 In the early 2000s, once-weekly pegylated forms of interferon were introduced. The combination of pegylated interferon with ribavirin increased SVR rates to more than 50% in patients with HCV genotype 1. However, HCV genotype 1 was less responsive than HCV genotype 2 or 3.9,10 Because of this variability in HCV response, low response rates in common HCV subpopulations (ie, black patients, patients with cirrhosis), and side effects associated with interferon and ribavirin, there remained a need to develop novel antiviral therapies.8 The treatment options for patients with HCV have evolved significantly in the past several years. In 2011, 2 first-generation protease inhibitors, telaprevir and boceprevir (also known as direct-acting antiviral drugs), were approved by the US Food and Drug Administration (FDA). 11,12 Both agents offered significant efficacy in patients with HCV genotype 1 infection as measured by SVR rates.11,12 In December 2013, the FDA approved sofosbuvir (Sovaldi) in combination with ribavirin—the first interferon-free, all-oral regimen—for the treatment of patients with HCV genotype 2 or 3.13,14 In addition, sofosbuvir in combination with interferon and ribavirin is approved for the treatment of patients with HCV genotype 1 and genotype 4.13,14 Candidates for sofosbuvir therapy include patients with hepatocellular carcinoma who meet Milan criteria (ie, awaiting liver transplantation) and patients with HCV/HIV-1 coinfection.13,14 Sofosbuvir regimens require less treatment time than older combination regimens—12 weeks for patients with HCV genotype 1, 2, or 4; and 24 weeks for patients with HCV genotype 3.14 In October 2014, the FDA approved the fixed-dose combination capsule of ledipasvir and sofosbuvir (Harvoni) for the treatment of patients with HCV genotype 1 infection.15 This once-daily combination tablet was the first regimen approved for HCV genotype 1 without interferon or ribavirin.15 Interest in novel therapies for HCV remain strong in light of the increasing incidence of HCV (and its costly complications), unmet patient needs, and the identification of new drug targets.16 Efforts continue, with the goals of improving the pharmacokinetics and the tolerability of these agents, as well as determining treatment strategies––interferon-containing and interferon-free (all oral) regimens––that optimize outcomes.17