Hepatitis C Drugs: The End of the Pegylated Interferon Era and the Emergence of All-Oral, Interferon-Free Antiviral Regimens: A Concise Review

Abstract

Between 2001 and 2011, the standard of care for chronic hepatitis C virus (HCV) infection was a combination of pegylated interferon (PEG-IFN) and ribavirin (RBV). In May 2011, boceprevir and telaprevir, two first-generation NS3/4A protease inhibitors, were approved in combination with PEG-IFN and RBV for 24 to 48 weeks in hepatitis C virus genotype 1 infections. In December 2013, simeprevir, a second-generation NS3/4A protease inhibitor, was approved for use with PEG-IFN and RBV for 12 weeks in genotype 1, while sofosbuvir, a NS5B nucleotide polymerase inhibitor, was approved for use with PEG-IFN and RBV for 12 weeks in genotypes 1 and 4, as well as with RBV alone for 12 weeks in genotype 2 and for 24 weeks in genotype 3. Sofosbuvir combined with simeprevir or an NS5A replication complex inhibitor (ledipasvir or daclatasvir) with or without RBV for 12 weeks in genotype 1 resulted in a sustained virological response >90%, irrespective of previous treatment history or presence of cirrhosis. Similarly impressive sustained virological response rates have been shown with ABT-450/r (ritonavir-boosted NS3/4A protease inhibitor)-based regimens in combination with other direct-acting antiviral agent(s) with or without RBV for 12 weeks in genotype 1. The optimal all-oral interferon-free antiviral regimen likely entails a combination of an NS5B nucleotide polymerase inhibitor with either a second-generation NS3/4A protease inhibitor or an NS5A replication complex inhibitor with or without RBV. Further research is needed to determine the role of resistance testing, clarify the optimal follow-up duration post-treatment, and evaluate the antiviral efficacy and safety in difficult-to-cure patient populations.

Efficacy of Sofosbuvir Plus Ribavirin With or Without Peginterferon-Alfa in Patients With Hepatitis C Virus Genotype 3 Infection and Treatment-Experienced Patients With Cirrhosis and Hepatitis C Virus Genotype 2 Infection

“…[13][14][15] One of the main reasons that interferon was so difficult for patients to tolerate was the length of treatment-most interferon-based regimens had durations of six months to a year, at the end of which patients were faced with a relatively high likelihood of relapse. With a shorter duration of 12 weeks and greater efficacy, the side effects of interferon have proven to be less formidable.…”

Hepatitis C and its impact on renal transplantation

“…35 Some DAAs have already been approved by the FDA, with 12 having reached phase II or III clinical trials. 50,51 The first therapeutic drugs to be introduced were the NS3/4A protease inhibitors telaprevir 50 and boceprevir, 51 which target the initial developmental stage of the HCV life cycle and are specific for HCV genotype 1 with a high antiviral efficacy. FDA approval for these drugs was obtained for their use in combination with pegylated interferon and ribavirin in 2011, 8 and the initial observed sustained viral response rates were up to 75% among pre viously untreated patients.…”

Are new models needed to optimize the utilization of new medicines to sustain healthcare systems?

“…As mentioned, funding new effective treatments for patients with HCV is a growing concern with more than150 to 185 million people worldwide believed to be infected with chronic HCV, high cure rates with second generation directly acting antivirals (DAAs) and associated costs (6,14,84,85). For instance in Malaysia, the prevalence of HCV is estimated at 1.5% of the population (86).…”

“…Cure rates of up to 95% are now seen with second generation DAAs, sofosbuvir and semiprevir, providing shorter treatment courses as well as reducing side effects compared with current treatments (6,14,40,87). Sofosbuvir combined with ledipasvir (HARVONI) has also achieved high cure rates with almost universal viral clearance after 8 weeks without the need for either pegylated interferons or ribavirin (84,85).…”