Simeprevir plus sofosbuvir (12 and 8 weeks) in hepatitis C virus genotype 1‐infected patients without cirrhosis: OPTIMIST‐1, a phase 3, randomized study

Abstract

Effective antiviral therapy is essential for achieving sustained virological response (SVR) in hepatitis C virus (HCV)‐infected patients. The phase 2 COSMOS study reported high SVR rates in treatment‐naive and prior null‐responder HCV genotype (GT) 1‐infected patients receiving simeprevir+sofosbuvir±ribavirin for 12 or 24 weeks. OPTIMIST‐1 (NCT02114177) was a multicenter, randomized, open‐label study assessing the efficacy and safety of 12 and 8 weeks of simeprevir+sofosbuvir in HCV GT1‐infected treatment‐naive and treatment‐experienced patients without cirrhosis. Patients were randomly assigned (1:1; stratified by HCV GT/subtype and presence or absence of NS3 Q80K polymorphism [GT1b, GT1a with Q80K, GT1a without Q80K]), prior HCV treatment history, and IL28B GT [CC, non‐CC]) to simeprevir 150 mg once daily+sofosbuvir 400 mg once daily for 12 or 8 weeks. The primary efficacy endpoint was SVR rate 12 weeks after end of treatment (SVR12). Superiority in SVR12 was assessed for simeprevir+sofosbuvir at 12 and 8 weeks versus a composite historical control SVR rate. Enrolled were 310 patients, who were randomized and received treatment (n = 155 in each arm). SVR12 with simeprevir+sofosbuvir for 12 weeks (97% [150/155; 95% confidence interval 94%‐100%]) was superior to the historical control (87%). SVR12 with simeprevir+sofosbuvir for 8 weeks (83% [128/155; 95% confidence interval 76‐89%]) was not superior to the historical control (83%). The most frequent adverse events were nausea, headache, and fatigue (12‐week arm: 15% [23/155], 14% [22/155], and 12% [19/155]; 8‐week arm: 9% [14/155], 17% [26/155], and 15% [23/155], respectively). No patients discontinued treatment due to an adverse event. One (1%, 12‐week arm) and three (2%, 8‐week arm) patients experienced a serious adverse event (all unrelated to study treatment). Conclusion: Simeprevir+sofosbuvir for 12 weeks is highly effective in the treatment of HCV GT1‐infected patients without cirrhosis, including those with Q80K. (Hepatology 2016;64:370‐380)

Baseline HCV‐RNA levels in genotype 1 chronic hepatitis C patients: The role of different cut‐off points

“…SVR12 with simeprevir plus sofosbuvir for 12 weeks without ribavirin was 97% (150 of 155) and the global SVR 12 weeks posttreatment (SVR12) with simeprevir plus sofosbuvir for 8 weeks without ribavirin 83% (128 of 155). (1) The global SVR12 rate achieved with 8 weeks of simeprevir plus sofosbuvir was lower than that observed after 8 weeks of treatment with sofosbuvir plus ledipasvir in HCV GT1-infected patients without cirrhosis. (2) However, this was not a head-tohead comparison, and the patient populations were different, because OPTIMIST-1 included treatmentexperienced patients.…”

“…We would like to congratulate Kwo et al (1) on their recent clinical trial with simeprevir plus sofosbuvir. Their important article has demonstrated high sustained virological response (SVR) rates among hepatitis C virus (HCV) genotype 1 (GT1) patients without cirrhosis who received simeprevir plus sofosbuvir in the OPTIMIST-1 trial.…”

“…Nonalcoholic fatty liver disease (NAFLD) is a common cause of CLD and its prevalence continues to rise in parallel with the growing obesity epidemic. (1)(2)(3) The aim of this study was to estimate changes in NAFLD prevalence among U.S. young adults and to assess factors associated with suspected NAFLD.…”

Resistance to Direct-Acting Antiviral Agents in Treatment of Hepatitis C Virus Infections

“…Indeed, several factors determine the impact of RASs on SVR including susceptibility/ fitness of a given viral population, patients' genetic identity, presence of liver cirrhosis, as well as treatment regimen and duration. In patients infected with genotype 1a, the efficacy of simeprevir + SOF treatment for 8 weeks has been significantly reduced to 73% SVR in the presence of NS3 Q80K substitution compared with 84% in the absence of this substitution [41]. The RAV test is then recommended and is in fact crucial to detect the prevalence of the common NS3 Q80K RAV that affects simeprevir efficacy in the HCV genotype 1a cirrhotic patients.…”

HCV Treatment Failure in the Era of DAAs

“…When Sofosbuvir/Daclatasvir combination was used, the presence of NS5A baseline RAVs is associated with reduced rates of SVR in undertreated (too short duration, no ribavirin) patients with cirrhosis and genotype 3 infection [12]. In addition, the presence of NS3 protease RAS Q80K was associated with a reduced rate of SVR in patients with HCV genotype 1a infection and cirrhosis, especially if they failed to respond to previous pegylated IFN-based treatment [13,14].…”