FDA

• Simeprevir was withdrawn from the U.S. market in 2018 due to obsoleteness as newer anti-HCV agents were approved. These agents are active against multiple genotypes and are better tolerated. It was also removed from the WHO Essential Medications List.
• Combined with Peg-IFN and ribavirin, simeprevir is FDA-indicated for treating HCV genotype 1 in patients with compensated liver disease (including cirrhosis).
• Since lower efficacy has been observed in some studies in patients infected with HCV genotype 1a with NS3 Q80K* polymorphism, screening for this polymorphism at baseline is recommended if simeprevir use is planned.
• If NS3 Q80K polymorphism is detected, the use of an alternative directly acting HCV regimen should be considered.

*In clinical trials, the prevalence of Q80K polymorphism was observed in 30% of patients infected with HCV genotype 1a and only 0.5% in patients infected with HCV genotype 1b.

NON-FDA APPROVED USES

Simeprevir plus sofosbuvir +/- ribavirin is a recommended first-line regimen for treating HCV genotype 1a and 1b. NS3 Q80K polymorphism for genotype 1a did not significantly impact sustained virologic response to this regimen.