Results from RESTORE , a phase III, multicentre, single-arm, open-label study presented at the International Liver Congress 2014 showed that Simeprevir ( Olysio )150 mg once-daily for 12 weeks in combination with Peginterferon and Ribavirin ( followed by 12 or 36 weeks of Peginterferon and Ribavirin ) was effective and well tolerated in hepatitis C virus ( HCV ) genotype 4-infected patients, consistent with previous observations in HCV genotype 1-infected patients.
Overall, 65.4% of patients has achieved SVR12 ( 82.9% of treatment-naïve, 86.4% of prior-relapser, 60.0% of prior partial-responder and 40.0% of prior null-responder patients ).
The rapid virological response ( RVR ) rates in the IL28B CT and TT patient sub-groups were 65.5% and 62.2%, respectively, while 65.6% and 59.5% achieved SVR12, respectively.
Among those patients with more severe liver fibrosis ( METAVIR score F4 ), 62.1% and 46.7% achieved RVR and SVR12, respectively.
Response-guided therapy criteria used to identify patients eligible for a total treatment duration of 24 weeks were met by 88.6% and 90.9% of treatment-naïve and prior-relapser patients, respectively. Among them, 93.5% and 95.0%, respectively, achieved SVR12.
No patients meeting response-guided therapy criteria experienced on-treatment failure, while three patients experienced viral relapse ( treatment-naive, n=2; relapsers, n=1 ).
Although HCV genotype 4 is mainly found in the Middle East, Egypt and Central Africa, it has recently spread in several Western countries, particularly in Europe, with rates of 10% to 24%.
Overall Simeprevir was well tolerated; most adverse events ( AEs ) were grade 1 or 2. Serious adverse reactions were infrequent ( five patients [ 4.7% ]; no deaths ) and considered unrelated to Simeprevir.
Most frequent adverse reactions ( greater than 30% of patients ) included influenza-like illness, asthenia and fatigue.
In this phase III study conducted in France and Belgium, 107 patients with chronic HCV genotype 4 received Simeprevir once daily with Peginterferon and Ribavirin for 12 weeks.
Treatment-naïve and prior-relapser patients received response-guided therapy with Peginterferon and Ribavirin continued for up to 24 or 48 weeks.
Prior partial responders and prior null responders continued to receive Peginterferon and Ribavirin for 48 weeks.
Out of a total patient population of 107 patients, 35 were treatment-naïve, 22 relapsers, 10 partial responders, and 40 null responders.
The demographics of the patient population were as follows: 78.5% male; median age, 49 years; 28.0% black; 28.8% METAVIR F4; 92.5% IL28B non-CC host genotype; and 42.5/23.6/33.9% HCV GT4a/4d/4 other genotype.
Simeprevir is an NS3/4A protease inhibitor with antiviral activity against HCV genotypes 1, 2, 4, 5 and 6, and approved in Japan, Canada, the United States and Russia for the treatment of chronic hepatitis C infection in combination with Pegylated Interferon and Ribavirin in HCV genotype 1-infected patients with compensated liver disease, including cirrhosis. Taken as one capsule, once-daily, Simeprevir works by blocking the protease enzyme that enables HCV to replicate in host cells.
Source: European Association for the Study of the Liver ( EASL ), 2014