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Grazoprevir/Elbasvir Combo Shows High Sustained Virologic Responses in HCV Trials

New drug application expected by June 2015

Promising data have been reported from the ongoing C-EDGE pivotal phase III clinical trial program evaluating the investigational once-daily tablet grazoprevir/elbasvir 100 mg/50 mg (Merck) in patients with or without cirrhosis who are infected with chronic hepatitis C virus (HCV) genotype (GT) 1, 4, or 6.

Patients in both the HCV-infected, treatment-naïve (C-EDGE TN) and human immunodeficiency virus (HIV)/HCV co-infected, treatment-naïve (C-EDGE CO-INFXN) trials treated for 12 weeks achieved rates of sustained virologic response 12 weeks after the completion of treatment (SVR12) of 95% (299/316 and 207/218, respectively). In addition, HCV-infected, treatment-experienced patients (C-EDGE TE) treated with or without ribavirin (RBV) for 12 weeks achieved SVR12 rates of 94% (98/104) and 92% (97/105), respectively, and those treated for 16 weeks achieved SVR12 rates of 97% (103/106) and 92% (97/105), respectively.

The new data were published online April 24 in the Annals of Internal Medicine.

C-EDGE TN is a randomized, blinded, placebo-controlled trial evaluating the efficacy and safety of grazoprevir/elbasvir in treatment-naïve patients with or without cirrhosis infected with chronic HCV GT 1, 4, or 6 who received therapy for 12 weeks. The patients were randomly assigned to an immediate-treatment group, which received grazoprevir/elbasvir for 12 weeks, or to a deferred-treatment group, which received placebo for 12 weeks, was followed for an additional 4 weeks, and then received open-label grazoprevir/elbasvir for the next 12 weeks. The primary efficacy analysis included 316 patients who received immediate treatment with grazoprevir/elbasvir or placebo. Of these patients, 50% were infected with GT 1a; 42% with GT 1b; 6% with GT 4; and 3% with GT 6. Overall, 22% of the patients had liver cirrhosis.

In this study, virologic failure occurred in 13 patients (4%) in the immediate-treatment group, including one virologic breakthrough and 12 virologic relapses. Serious adverse events (AEs) occurred in nine (3%) and three (3%) patients in the immediate-treatment and corresponding placebo arms, respectively; none was considered drug-related. The most common AEs in the immediate-treatment and corresponding placebo groups included headache (17% and 18%, respectively), fatigue (16% and 17%), nausea (9% and 8%), and arthralgia (6% and 6%).

C-EDGE CO-INFXN is an open-label, single-arm study evaluating the efficacy and safety of grazoprevir/elbasvir in treatment-naïve patients with or without cirrhosis infected with chronic HCV GT 1, 4, or 6 and HIV who received therapy for 12 weeks. Of the 218 patients enrolled in the trial, 66% were infected with HCV GT 1a; 21% with GT 1b or other GT 1; 13% with GT 4; and 1% with GT 6. Overall, 16% of patients had liver cirrhosis.

In this study, virologic failure occurred in seven patients (3%), including six virologic relapses and one re-infection. There were no reported drug-related serious AEs. The most common AEs were fatigue (13%), headache (12%), and nausea (9%).

C-EDGE TE is a randomized study evaluating the efficacy and safety of once-daily grazoprevir/elbasvir with or without twice-daily RBV in treatment-experienced (prior null response, partial response, or relapse with peg-interferon/RBV) patients with or without cirrhosis infected with chronic HCV GT 1, 4, or 6 who received therapy for 12 or 16 weeks.

Of the 209 patients randomly assigned to the 12-week arms, 105 received grazoprevir/elbasvir only, and 104 patients received grazoprevir/elbasvir plus RBV. Patients in the grazoprevir/elbasvir-only arm comprised 58% GT 1a; 33% GT 1b or other GT 1; and 9% GT 4. Overall, 35% of the patients had liver cirrhosis. Among the 104 patients receiving grazoprevir/elbasvir plus RBV, 58% were infected with chronic HCV GT 1a; 28% with GT 1b or other G T1; and 14% with GT 4. Overall, 34% had liver cirrhosis.

In the grazoprevir/elbasvir-only and grazoprevir/elbasvir-plus-RBV arms, six patients (6%) in each arm were reported to have a virologic relapse. No patients were reported to have virologic breakthrough or rebound. Serious AEs were reported in four patients (4%) in the grazoprevir/elbasvir-only arm and in three patients (3%) in the grazoprevir/elbasvir-plus-RBV arm. The most common AEs in the grazoprevir/elbasvir-only and grazoprevir/elbasvir-plus-RBV arms, respectively, were fatigue (19% and 27%), headache (21% and 20%) and nausea (9% and 14%).

Of the 211 patients enrolled in the 16-week arms, 105 received grazoprevir/elbasvir only and 106 received grazoprevir/elbasvir plus RBV. In the grazoprevir/elbasvir-only arm, 46% of the patients were infected with chronic HCV GT 1a; 46% with GT 1b or other GT 1; 5% with GT 4; and 4% with GT 6. Overall, 36% of the patients had liver cirrhosis. Among those in the grazoprevir/elbasvir-plus-RBV arm, 55% were infected with chronic HCV GT 1a; 36% with GT 1b or other GT 1; 8% with GT 4; and 2% with GT 6. Overall, 35% had liver cirrhosis.

Among the patients receiving grazoprevir/elbasvir only, three patients (3%) were reported to have virologic breakthrough or rebound and four patients (4%) were reported to have virologic relapse. No virologic failures occurred in patients receiving grazoprevir/elbasvir plus RBV. Serious AEs were reported in three patients (3%) in the grazoprevir/elbasvir-only arm and in four patients (4%) in the grazoprevir/elbasvir-plus-RBV arm. The most common AEs in the grazoprevir/elbasvir-only and grazoprevir/elbasvir-plus-RBV arms, respectively, were fatigue (16% and 30%), headache (19% and 19%) and nausea (4% and17%).

Source: Merck; April 24, 2015.

 

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