Indications
Mavixen 100 mg & 40 mg (Glecaprevir & Pibrentasvir)
This is a fixed-dose combination of glecaprevir, a hepatitis C virus (HCV) NS3/4A protease inhibitor, and pibrentasvir,
an HCV NS5A inhibitor, and is indicated for the treatment of patients with chronic HCV genotype (GT) 1, 2, 3, 4, 5 or 6
infection without cirrhosis and with compensated cirrhosis (Child-Pugh A). This is also indicated for the treatment of
adult patients with HCV genotype 1 infection, who previously have been treated with a regimen containing an HCV
NS5A inhibitor or an NS3/4A protease inhibitor, but not both.
Pharmacology
Glecaprevir is an inhibitor of the HCV NS3/4A protease, which is a viral enzyme necessary for the proteolytic cleavage
of the HCV-encoded polyprotein into mature forms of the NS3, NS4A, NS4B, NS5A, and NS5B proteins. These
multifunctional proteins, including NS3, are essential for viral replication. The N-terminal of NS3 protein confers
serine protease activity, while the C-terminus of NS3 encodes a DExH/D-box RNA helicase which hydrolyzes NTP as
an energy source to unwind double-stranded RNA in a 3′ to 5′ direction during replication of viral genomic RNA. NS4A
is a cofactor for NS3 that directs the localization of NS3 and modulates its enzymatic activities. Glecaprevir disrupts
the intracellular processes of the viral life cycle by inhibiting the NS3/4A protease activity of cleaving
downstream junctions of HCV polypeptide and proteolytic processing of mature structural protein.
NS5A is a phosphoprotein that plays an essential role in the replication, assembly, and maturation of infectious viral
proteins. The basal phosphorylated form of NS5A, which is maintained by the C-terminal serine cluster, is key in ensuring
its interaction with the viral capsid protein, or the core protein. By blocking this interaction, pibrentasvir inhibits the
assembly of proteins and the production of mature HCV particles. NS5A also interacts with viral and cellular proteins to
form the HCV replicate complex, and supports the RNA replication of HCV
