Simeprevir improves rates of sustained virologic response and may allow for a 24-week treatment duration when added to interferon-based therapy for chronic hepatitis C, according to data presented at the International Liver Congress in Amsterdam.
In the double blind, phase 3 QUEST-1 study, researchers randomly assigned 394 treatment-naive patients with HCV genotype 1 to either 150 mg oral HCV NS3/4A protease inhibitor simeprevir or placebo, for 12 weeks, plus 48 weeks of pegylated interferon alfa-2a with ribavirin (PR). Patients with HCV RNA below 25 IU/mL after 4 weeks of treatment and undetectable RNA at 12 weeks stopped treatment at 24 weeks. All placebo recipients received 48 weeks of PR therapy.
Rapid virologic response occurred in 80% of simeprevir recipients and 12% of the placebo group. Sustained virologic response at 12 weeks after treatment was achieved by 80% of the simeprevir group and 50% of placebo recipients (P<.001). Most simeprevir recipients (85%) stopped treatment at 24 weeks. Patients treated with simeprevir experienced less on-treatment failure (9% vs. 34% of cases) and less relapse (9% vs. 21%).
Similar results were observed in the QUEST-2 study, in which researchers randomly assigned 391 treatment-naive patients to simeprevir or placebo in addition to therapy with peginterferon alfa-2a or alfa-2b with ribavirin. In this trial, RVR occurred in 79% of simeprevir recipients and 13% of the placebo group, and SVR at 12 weeks occurred in 81% of the simeprevir group and 50% of placebo recipients (P<.001). Most patients in the simeprevir group (91%) were able to stop therapy after 24 weeks. Rates of on-treatment failure (7% vs. 32%) and relapse (13% vs. 24%) also were lower among simeprevir recipients.
In QUEST-1, commonly reported adverse events included headache, fatigue and pruritus, with 3% of simeprevir recipients discontinuing treatment due to adverse events. Common events in the QUEST-2 trial included headache, fatigue, pruritus and flu-like illness, with similar incidence rates of adverse events regardless of the type of peginterferon administered.
“Simeprevir 150 mg QD was well tolerated, leading to a high SVR 12 rate … when administered with either [peginterferon alfa-2a or -2b],” the researchers wrote. “The majority of patients receiving simeprevir [were] able to shorten therapy to 24 weeks.”
For more information:
Jacobson I. #1425: Simeprevir (TMC435) With Peginterferon/Ribavirin for Chronic HCV Genotype-1 Infection in Treatment-Naive Patients: Results from QUEST-1, a Phase III Trial. Presented at: The International Liver Congress 2013; April 24-28, Amsterdam.
Manns M. #1413: Simeprevir (TMC435) With Peginterferon/Ribavirin for Treatment of Chronic HCV Genotype-1 Infection in Treatment-Naive Patients: Results from QUEST-2, a Phase III Trial. Presented at: The International Liver Congress 2013; April 24-28, Amsterdam.