Date: 2014-07-28
Type of information: Publication of results in a medical journal
phase: 2
Announcement: publication of results in the Lancet
Company: Medivir (Sweden) Janssen Pharmaceutical (J&J - USA)
Product: simeprevir (TMC435) and sofosbuvir (GS7977)
Action
mechanism: direct-acting antiviral agent/nucleotide analog. Sofosbuvir is an oral nucleotide analog inhibitor of the HCV NS5B polymerase enzyme, which plays an essential role in HCV replication. This direct-acting agent interferes directly with the HCV life cycle by suppressing viral replication. This nucleotide NS5B polymerase inhibitor is developed by Gilead Sciences. Simeprevir is an NS3/4A protease inhibitor jointly developed by Janssen R&D Ireland and Medivir.
Disease: genotype 1 chronic hepatitis C virus
Therapeutic area: Infectious diseases
Country:
Trial
details: The open-label, randomised Phase 2 COSMOS study investigated the efficacy and safety of 12 or 24 weeks of simeprevir (150 mg once daily) with sofosbuvir (400 mg once daily) without or with RBV in HCV genotype 1 chronically infected patients with compensated liver disease. The study included two cohorts: Cohort 1 included null-responder patients with no to moderate liver fibrosis (defined as METAVIR F0 to F2 scores) and Cohort 2 included treatment-naïve and prior null-responder patients with advanced fibrosis, including cirrhosis (defined as METAVIR F3 to F4 scores). Cohort 1 included a total of 80 HCV GT1 prior null responders to PegIFN/RBV therapy with METAVIR score F0-F2, who were stratified by IL28B status and genotype 1 subtype, into one of four arms including once-daily simeprevir (150 mg) plus sofosbuvir (400 mg) for 24 weeks with or without ribavirin, or once-daily simeprevir (150 mg) plus sofosbuvir (400 mg) for 12 weeks with or without ribavirin.
Cohort 2 of the study investigated similar treatment regimens and durations in genotype 1 prior null-responder and treatment-naïve patients with METAVIR scores of F3-F4. The Metavir score is used to quantify the degree of inflammation and fibrosis of the liver. Liver fibrosis is scored on a four-point scale.
Latest
news: * On July 28, 2014, Medivir and J&J announced that results from the Phase 2 COSMOS (Combination Of SiMeprevir and sOfosbuvir in HCV genotype 1 infected patientS) clinical study were published July 28 in The Lancet, demonstrating that 92 percent of genotype 1 chronic hepatitis C virus (HCV) adult patients treated with Janssen R&D Ireland\'s (Janssen) simeprevir, an NS3/4A protease inhibitor, in combination with sofosbuvir, achieved sustained virologic response 12 weeks after the end of treatment (SVR12), including those patients with compensated cirrhosis and prior null response to treatment with pegylated interferon (PegIFN) and ribavirin (RBV). According to findings from the study, the all-oral 12-week, interferon-free treatment regimen with simeprevir and sofosbuvir resulted in consistent SVR12 rates regardless of degree of fibrosis, and was an effective and well-tolerated therapeutic regimen in both treatment-naïve and prior null-responder patients. In Cohort 1 (N=80), 93 percent and 96 percent of genotype 1 HCV patients with no to moderate liver fibrosis who were prior null responders to PegIFN + RBV treated with simeprevir and sofosbuvir for 12 weeks without or with RBV, respectively, achieved SVR12. Additionally, in Cohort 2 (N=87), 93 percent of treatment-naïve and prior null-responder patients with genotype 1 HCV and advanced liver fibrosis treated with simeprevir and sofosbuvir for 12 weeks without or with RBV, respectively, achieved SVR12. In the COSMOS trial, the most common ( > 10 percent) adverse events reported during treatment with simeprevir in combination with sofosbuvir without and with RBV were fatigue (31 percent), headache (20 percent), and nausea (16 percent). Based on the findings from the COSMOS study, in April 2014, Janssen announced initiation of the Phase 3 OPTIMIST-1 and OPTIMIST-2 trials examining the safety and efficacy of simeprevir and sofosbuvir without interferon or RBV for the treatment of chronic genotype 1 HCV infection. "Simeprevir plus sofosbuvir, with or without ribavirin, to treat chronic infection with hepatitis C virus genotype 1 in non-responders to pegylated interferon and ribavirin and treatment-naive patients: the COSMOS randomised study". Prof Eric Lawitz MD et al. The Lancet, Early Online Publication, 28 July 2014 doi:10.1016/S0140-6736(14)61036-9
