Description

Sofosbuvir + Velpatasvir (trade name Epclusa) is a fixed-dose combination tablet containing two direct-acting antiviral (DAA) medications. It is a highly effective, one-pill, once-daily regimen for the treatment of chronic hepatitis C virus (HCV) infection. The combination therapy targets two different viral proteins, providing a powerful synergistic effect that leads to very high cure rates.

Indication

Sofosbuvir/velpatasvir is a pangenotypic treatment, meaning it is effective against all six major genotypes of the hepatitis C virus (genotypes 1, 2, 3, 4, 5, and 6). This simplifies treatment decisions by eliminating the need for complex genotype testing for many patients.

The combination is indicated for the treatment of:

• Adults and pediatric patients (typically 3 years of age and older) with chronic hepatitis C without cirrhosis or with compensated cirrhosis.

• Patients with decompensated cirrhosis, for whom the regimen is used in combination with ribavirin.

• Patients who have been previously treated for HCV and those who are treatment-naïve.

Mechanism of Action

The strength of this combination lies in its dual mechanism of action, which targets two distinct and essential viral proteins, making it very difficult for the virus to develop resistance.

1. Sofosbuvir: As a nucleotide analog, sofosbuvir is a prodrug that is converted to its active triphosphate form within the body. This active form, GS-461203, acts as a competitive inhibitor of the HCV RNA-dependent RNA polymerase (NS5B). This enzyme is crucial for the replication of the viral genome. By being incorporated into the new viral RNA strand, sofosbuvir acts as a chain terminator, stopping the replication process.

2. Velpatasvir: Velpatasvir is an inhibitor of the HCV non-structural protein 5A (NS5A). NS5A is a non-enzymatic protein that plays a key role in both viral RNA replication and the assembly of new viral particles. By binding to NS5A, velpatasvir disrupts the formation of the viral replication complex and prevents the assembly of infectious virions.

By combining these two drugs, the treatment regimen attacks the hepatitis C virus at two different stages of its life cycle, leading to a sustained virologic response (SVR), which is considered a cure, in over 90% of patients.