NEW ORLEANS, LA—For patients with hepatitis C virus (HCV) infection genotype (GT) 1–6, treatment with sofosbuvir/velpatasvir plus voxilaprevir (GS-9857) once daily was safe, well tolerated, and highly effective in treatment-naive and treatment-experienced patients, reported Ronald Nahass, MD, FIDSA, FSHEA, from ID Care, Inc., Hillsborough, NJ, at IDWeek 2016.
Sofosbuvir is a nucleotide analog NS5B polymerase inhibitor; velpatasvir, a pangenotypic NS5A inhibitor; and voxilaprevir, an investigational pangenotypic NS3/4A protease inhibitor. All are potent direct-acting antiviral agents (DAAs) with distinct viral targets and high barriers to resistance.
The sofosbuvir/velpatasvir fixed-dose combination (400/100mg) tablet plus voxilaprevir 100mg tablet is taken orally, once daily.
This 3-drug combination may both “offer an opportunity to shorten treatment duration in treatment-naïve patients” and “provide a suitable regimen for those who failed prior treatment with DAAs where there are limited re-treatment options,” Dr. Nahass said.
In two Phase 2 open-label studies, researchers evaluated these DAAs in both treatment-naive and treatment-experienced GT1–6 HCV-infected patients with or without cirrhosis. At IDWeek, Dr. Nahass presented data from an integrated analysis of the safety and efficacy of these studies.
Treatment-naive patients received the 3-drug combination for 6 weeks if they were noncirrhotic or 8 weeks if cirrhotic. Patients with virologic failure to prior pegylated-interferon (Peg-IFN) + ribavirin (for GT2–6) treatment or any DAA (for GT2–6), NS5A-inhibitor, or multiple classes of DAAs (for GT1) ± Peg-IFN ± ribavirin regimens were administered open-label with sofosbuvir/velpatasvir + voxilaprevir for 12 weeks.
The primary efficacy endpoint was SVR12, with HCV RNA <LLOQ at post-treatment week 12 (LLOQ 15 IU/mL). The safety endpoints were adverse events and discontinuations and laboratory abnormalities.
A total of 294 patients received sofosbuvir/velpatasvir plus voxilaprevir for 6 weeks (n=67), 8 weeks (n=31), or 12 weeks (n=128), and 31 patients received sofosbuvir/velpatasvir plus voxilaprevir plus ribavirin for 8 weeks.
The majority of the patients in each of the treatment groups was GT1, 52%, 70%, 100%, and 49%, respectively, and GT3, 31%, 18%, 0%, and 27%. None of the patients in the sofosbuvir/velpatasvir plus voxilaprevir treated for 6 weeks had cirrhosis, compared with 64%, 100%, and 48%, respectively, in the other 3 treatment groups.
Of the 128 patients with prior treatment experience, 52% (n=66) received non-NS5A agents; 27% (n=35) had received NS5As; and 21% (n=27) were DAA-naïve (GT2-6 who failed prior Peg-IFN + ribavirin regimens.
The integrated overall efficacy results showed that sofosbuvir/velpatasvir plus voxilaprevir for 8 and 12 weeks yielded high SVR12 rates without the need for ribavirin in both treatment-naïve and treatment-experienced patients with HCV GT1–6, Dr. Nahass said. At 8 weeks, SVR12 rates for those who were treatment-naïve and cirrhotic were 96% overall; with 97% for GT1, 94% for GT2, and 92% for GT2,4,6.
At 12 weeks, patients who were treatment-experienced, regardless of cirrhosis status, had SVR12 rates of 99% overall, 100% for GT1, 97% for GT3, and 100% for GT2,4,6. These SVR rates were high regardless of prior treatment exposure to a DAA.
“The potency is extraordinary,” Dr. Nahass said.
Similar SVR12 rates were observed for the sofosbuvir/velpatasvir plus voxilaprevir 8- and 12-week regimens regardless of cirrhosis status.
The 6-week treatment duration was associated with a higher relapse rate, except in GT3.
The presence of baseline resistance-associated variants (RAVs) had no impact on SVR rates. Of the 47% of patients (93 of 197) with baseline RAVs in the treatment-naïve group, SVR12 rates were 75% in the 6-week group, 96% in the 8-week group, and 77% in the group that also received ribavirin.
The integrated safety summary identified no new concerns. The most common adverse events were headache, nausea, fatigue, diarrhea, and anemia.
Dr. Nahass said the sofosbuvir/velpatasvir plus voxilaprevir fixed-dose combination for 8 to 12 weeks “is being evaluated in Phase 3 trials as a single-tablet regimen in DAA-experienced patients.”
The study was funded by Gilead Sciences, Inc.
Debra Hughes, MS (https://www.empr.com/author/debra-hughes-ms/)
MPR