Sofosbuvir Combo Highly Effective in HCV Genotypes 2, 3

The combination of sofosbuvir (SOF) and velpatasvir (VEL) showed promise treating hepatitis C virus (HCV) during a pair of phase 3 trials, noted a study published in the World Journal of Hepatology.

Since the approval of direct antiviral agents (DAAs), several oral regimens have been developed that combine DAAs from different families. These regimens show increased and sustained virological response rates in excess of 90%, reducing treatment duration to 12 weeks or less.

In particular, SOF/VEL has been investigated in the phase 3 trials ASTRAL-2 (for HCV genotype 2) and ASTRAL-3 (for HCV genotype 3). The goal of the ASTRAL program is to evaluate the safety and efficacy of SOF/VEL in patients with HCV genotypes 1 through 6, including patients with decompensated liver disease.

Both ASTRAL-2 and ASTRAL-3 were randomized, controlled, phase 3 trials with the same eligibility criteria, besides the HCV genotype. The 2 trials compared a fixed-dose combination tablet of SOF/VEL for 12 weeks with the standard treatment of SOF plus ribavirin (RVR) for 12 or 24 weeks in previously treated patients with HCV genotypes 2 and 3, and in untreated patients, including those with decompensated cirrhosis.

Participants were age 18 and older, and had at least a 6-month history of HCV infection with compensated liver disease. In each trial, patients with chronic HCV were randomized to receive either a fixed-dose combination tablet of 400-mg of SOF and 100-mg of VEL once daily for 12 weeks, or 400-mg of SOF plus RVR for 12 weeks in patients with HCV genotype 2, or 24 weeks for patients with genotype 3.

RVR was administered orally, twice daily, with body weight-determined doses. The primary endpoint was SVR defined as an HCV RNA level of less than 15 IU per milliliter at 12 weeks after the end of treatment.

The results of the ASTRAL-2 trial showed that patients who received SOF/VEL met the primary endpoint with no virologic failures. For the ASTRAL-3 trial, patients given SOF/VEL achieved SVR, but 4% showed virologic failure after treatment was completed.

Overall, researchers found that the rate of SVR was found to be higher in patients without cirrhosis who were not given any prior treatment. The rates of adverse events (AEs) in both trials were found to be lower in the group of patients who received SOF/VEL compared with those who received SOF/RVR.

Additionally, in both trials, only 1 patient who received SOF/VEL stopped treatment early due to adverse events, such as difficulty concentrating, headache, and anxiety. The most common AEs, such as nausea, fatigue, and headache were reported among between 10% to 38% of patients in the SOF/VEL group, together with cough, dyspepsia, insomnia, irritability, nasopharyngitis, and pruritus.

Serious AEs in the ASTRAL-2 trial for patients given SOF/VEL included abdominal pain, enteritis, and pneumonia. AEs in the ASTRAL-3 trial included acute myocardial infarction, acute cholecystitis, hematochezia, intracranial aneurysm, ruptured ovarian cyst, and food poisoning.

The findings from the ASTRAL-2 and ASTRAL-3 trials showed that SOF/VEL is highly effective against HCV genotypes 2 and 3, besides the virologic failure in 11 patients at the end of treatment in the ASTRAL-3 trial, and is reasonably safe, according to the study.

Treatment for HCV genotype 3 still remains a challenge, and more research needs to be done to increase the rate of SVR in this subtype of patients. Future trials that evaluat new DAAs should primarily focus on the prolongation of the SVR and the inclusion of HCV patients, who can gain real benefit from these new therapies, the study concluded.