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Epclusa: What Have We Learned?



ASTRAL-1 was a multicenter, double-blind, placebo-controlled trial. Patients 18 years or older with treated or untreated chronic HCV genotype 1, 2, 4, 5, or 6 were enrolled.12 Previously treated patients who received an interferon-containing regimen and did not achieve an SVR were targeted to ensure there was a mix of previously treated and treatment-naïve patients. Patients who had a history of hepatic decompensation or hepatocellular carcinoma, previously discontinued HCV treatment because of an AE, or received an NS5B inhibitor or any NS5A inhibitor were not eligible for enrollment. Those enrolled were randomly assigned in a 5:1 ratio to receive treatment with sofosbuvir/ velpatasvir or placebo, one tablet daily for 12 weeks. In addition, they were randomized according to genotype and whether or not cirrhosis was present. Patients with genotype 5 did not undergo randomization due to its low prevalence, so they were enrolled in the active treatment arm only. The primary endpoint of ASTRAL-1 was SVR at 12 weeks (SVR12), defined as an HCV RNA level <15 IU/mL at 12 weeks after the end of treatment in all patients who received at least one dose of sofosbuvir/velpatasvir or placebo. The secondary endpoints included the rate of AEs and treatment discontinuation because of AEs.12
Overall, patients who received 12 weeks of sofosbuvir/ velpatasvir achieved a 99% rate of SVR12. The rates of SVR12 were very similar regardless of HCV genotype. Rates of SVR12 were 98% for genotype 1a; 99% for genotype 1b; 100% for genotypes 2, 4, and 6; and 97% for genotype 5. Similarly, for patients with compensated cirrhosis and previously treated, the SVR rates were 99% and >99%, respectively.12


ASTRAL-2 and ASTRAL-3 were both multicenter, randomized, controlled, phase 3 trials that evaluated patients with chronic HCV.13 Patients enrolled in these trials were randomized in a 1:1 ratio to receive either sofosbuvir/velpatasvir for 12 weeks, standard therapy of sofosbuvir/ribavirin for 12 weeks if they had genotype 2, or standard therapy of sofosbuvir/ribavirin for 24 weeks if they had genotype 3. The doses of ribavirin were determined according to body weight and administered orally twice daily. The primary endpoint evaluated in these trials were the same as those evaluated in the ASTRAL-1 trial.13
In ASTRAL-2, SVR12 was observed in 99% of patients with genotype 2 who received sofosbuvir/velpatasvir, compared with 94% of those who received sofosbuvir/ ribavirin for 12 weeks, and was found to be statistically superior. In ASTRAL-3, SVR12 was obtained in 95% of patients with genotype 3 who received sofosbuvir/ velpatasvir versus 80% of those who received sofosbuvir/ ribavirin for 24 weeks. Once again, the SVR12 rate was superior in those treated with sofosbuvir/velpatasvir compared with those treated with standard therapy for genotype 3.13 

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