Simeprevir is a direct-acting hepatitis C virus (HCV) NS3/4A serine protease inhibitor that prevents viral replication.
Simeprevir can be used to treat patients infected with viral genotypes 1 and 4. It is taken in combination with peginterferon alfa and ribavirin in treatment-naive patients, patients who have relapsed following prior therapy and those who have not responded to previous treatment (including partial and null responders). It can also be given in combination with sofosbuvir (Sovaldi) in all patients with HCV genotype 1 or 4 regardless of prior therapy when interferon cannot be used or is not tolerated; ribavirin can be added to this two-drug regimen based on a clinical assessment of the individual patient.
Before treating patients with HCV genotype 1a, the manufacturer recommends testing the virus for the NS3 Q80K polymorphism as the efficacy of simeprevir is substantially reduced in the presence of this variant and alternative therapy should be considered.
Simeprevir was investigated in combination with peginterferon and ribavirin in the QUEST-1, QUEST-2 and PROMISE phase III clinical studies. All three studies met their primary endpoints, namely that the virological response rates were significantly higher in patients who received simeprevir plus peginterferon and ribavirin than in patients who received peginterferon and ribavirin alone.
Approval for the combination of simeprevir and sofosbuvir (with and without ribavirin) was based on positive data from the phase II COSMOS study.
Dr Andrew Ustianowski, Chair of the British Viral Hepatitis Group and Consultant in Infectious Diseases at North Manchester General Hospital welcomed simeprevir as "a well-tolerated and efficacious addition to our therapies against hepatitis C".
Further information: Janssen-Cilag