Simeprevir Phase 3 Trial Results

Orlando—Treatment-naïve patients with hepatitis C who took 150 mg of simeprevir once daily in combination with peginterferon and ribavirin had a significantly better sustained virological response (SVR) rate compared with those taking placebo, according to a phase 3, randomized, double-blind, placebo-controlled trial.

The SVR rate at 12 weeks was 80% in the simeprevir group and 50% in the placebo group (P<.001). Patients also tolerated the drug, which is an investigational protease inhibitor to treat genotype 1 chronic hepatitis C in adults with compensated liver disease.

Results were presented during a poster session at DDW. The poster was titled Simeprevir (TMC435) with Peginterferon/Ribavirin for Chronic HCV Genotype-1 Infection in Treatment-Naïve Patients: Results from QUEST-1, a Phase 3 Trial.

In May, the FDA granted priority review status to simeprevir. Janssen Research & Development, LLC, the drug’s manufacturer, said in a news release that the FDA’s review would begin approximately 60 days after receiving the new drug application. The FDA typically takes up to 6 months before deciding on approvals.  

In this trial, called QUEST-1, patients were randomized in a 2:1 ratio to receive simeprevir (n=264) or placebo (n=130) for 24 or 48 weeks. All patients took the drugs in combination with peginterferon and ribavirin. The groups were well balanced. The mean age was 48 years, and the median body mass index was 27 kg/m². Approximately 44% of patients were females, and 90% were white.

During the first 12 weeks of the study, 5% of patients in the simeprevir group and 3% of patients in the placebo group discontinued treatment. In addition, 6.8% of patients in the simeprevir group and 66.2% of patients in the placebo group met a virologic stopping rule at week 4, 12, 24, or 36.

The authors noted that 85% of patients who received simeprevir met the response-guided therapy (RGT) criteria to shorten therapy to 24 weeks. Of those patients, 91% achieved a SVR at week 12. Of the patients in the simeprevir group who did not meet RGT criteria, 21% achieved a SVR at week 12. RGT criteria were defined as hepatitis C virus RNA <25 IU/mL at week 4, undetectable hepatitis C virus RNA at week 12, and a stop in treatment at week 24.

In addition, the authors said that IL28B genotype, METAVIR score, and hepatitis C had an impact on SVR rates at week 12, although each of the differences favored patients who received simeprevir. At the end of the treatment period, 9% of patients in the simeprevir group and 34% of patients in the placebo group had detectable hepatitis C, which the authors considered as on-treatment failure.

During the first 12 weeks of treatment, 72% of patients in the simeprevir group and 65% of patients in the placebo group had a grade 1 or 2 adverse event, while 23% and 29% of patients in the respective groups had a grade 3 or 4 adverse event. In addition, 3% of patients who took simeprevir and 4% of patients who received placebo had a serious adverse event. In each group, 3% of patients had an adverse event that led to treatment discontinuation.

The most common adverse events in both groups were fatigue, headache, and pruritus. The prevalence of anemia and rash were similar in the groups.

This study was conducted and funded by Janssen Research & Development, LLC.