- Data Sets Include Treatment-Naïve, Treatment-Experienced and HIV Co-Infected Patients with Chronic Hepatitis C Virus Genotypes 1, 4 or 6 Infection
- Merck Remains on Track to Submit New Drug Application (NDA) to U.S. Food and Drug Administration (FDA) in First Half of 2015
“Patients with co-morbidities and varying treatment experiences represent important segments of the chronic hepatitis C population in need of additional innovative treatment options,” said Dr. Eric Lawitz, vice president, scientific and research development, The Texas Liver Institute and clinical professor of medicine, The University of Texas Health Science Center, San Antonio. “These findings are important because they demonstrate that a single pill of grazoprevir/elbasvir taken once-daily achieved consistently high rates of SVR12 in the patient populations studied.”
| Summary of SVR12 findings: C-EDGE TN, C-EDGE CO-INFXN, C-EDGE TE | ||||||||||||
| C-EDGE TN | C-EDGE CO-INFXN | C-EDGE TE | ||||||||||
| Without RBV (n=316) | Without RBV (n=218) | Without RBV (n=105) | With RBV (n=104) | Without RBV (n=105) | With RBV (n=106) | |||||||
| Duration | 12 weeks | 12 weeks | 12 weeks | 12 weeks | 16 weeks | 16 weeks | ||||||
| All Patients: | 95% | 95% | 92% | 94% | 92% | 97% | ||||||
| SVR12 | (299/316) | (207/218) | (97/105) | (98/104) | (97/105) | (103/106) | ||||||
| Cirrhotic | 97% | 100% | 89% | 89% | 92% | 100% | ||||||
| (68/70) | (35/35) | (33/37) | (31/35) | (35/38) | (37/37) | |||||||
| Non-cirrhotic | 94% | 94% | 94% | 97% | 93% | 96% | ||||||
| (231/246) | (172/183) | (64/68) | (67/69) | (62/67) | (66/69) | |||||||
| Genotype 1a | 92% | 94% | 90% | 93% | 94% | 95% | ||||||
| (144/157) | (136/144) | (55/61) | (56/60) | (45/48) | (55/58) | |||||||
| Genotype 1b or | ||||||||||||
| other Genotype | 99% | 96% | 100% | 97% | 96% | 100% | ||||||
| 1 | (129/131) | (43/45) | (35/35) | (28/29) | (46/48) | (38/38) | ||||||
| Genotype 4 | 100% | 96% | 78% | 93% | 60% | 100% | ||||||
| (18/18) | (27/28) | (7/9) | (14/15) | (3/5) | (8/8) | |||||||
| Genotype 6 | 80% | 100% | 75% | 100% | ||||||||
| (8/10) | (1/1) | N/A | N/A | (3/4) | (2/2) | |||||||
C-EDGE TN Overview and Additional Findings
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 GT1, 4 or 6 who received therapy for 12 weeks. Patients were randomized to an immediate treatment group that received grazoprevir/elbasvir for 12 weeks or to a deferred treatment group that received placebo for 12 weeks, were followed for an additional four weeks, and then received open label grazoprevir/elbasvir for the next 12 weeks. The primary efficacy analysis included those patients who received immediate treatment with grazoprevir/elbasvir or placebo. Of the 316 patients who received immediate treatment with grazoprevir/elbasvir, 50 percent were infected with GT1a, 42 percent with GT1b, six percent with GT4 and three percent with GT6. Overall, 22 percent of 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 occurred in nine (3%) and three (3%) patients in the immediate treatment and corresponding placebo arms, respectively; none were considered drug-related. The most common adverse events reported (greater than 5% incidence) in the immediate treatment and corresponding placebo groups, were headache (17%, 18%), fatigue (16%, 17%), nausea (9%, 8%) and arthralgia (6%, 6%), respectively.
C-EDGE CO-INFXN Overview and Additional Findings
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 GT1, 4 or 6 and HIV who received therapy for 12 weeks. Of the 218 patients enrolled in the trial, 66 percent were infected with HCV GT1a, 21 percent with GT1b or other GT1, 13 percent with GT4, and one percent with GT6. Overall, 16 percent of patients had liver cirrhosis.
In this study, virologic failure occurred in seven patients (3%), including six virologic relapses and one reinfection. There were no reported drug-related serious adverse events. The most common (greater than 5% incidence) adverse events reported were fatigue (13%), headache (12%) and nausea (9%).
C-EDGE TE Overview and Additional Findings
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 GT1, 4 or 6 who received therapy for 12 weeks or 16 weeks.
12 week arms
Of the 209 patients randomized to the 12 week arms, 105 patients received grazoprevir/elbasvir only and 104 patients received grazoprevir/elbasvir plus RBV. Patients in the grazoprevir/elbasvir only arm comprised 58 percent GT1a, 33 percent GT1b or other GT1 and nine percent GT4. Overall, 35 percent had liver cirrhosis. Among the 104 patients receiving grazoprevir/elbasvir plus RBV, 58 percent were infected with chronic HCV GT1a, 28 percent GT1b or other GT1, and 14 percent GT4. Overall, 34 percent had liver cirrhosis.
In the grazoprevir/elbasvir only and grazoprevir/elbasvir plus RBV arms, six patients in each arm (6%) were reported to have virologic relapse. No patients were reported to have virologic breakthrough or rebound. Serious adverse events were reported in four patients in the grazoprevir/elbasvir only arm (4%) and three patients in the grazoprevir/elbasvir plus RBV arm (3%). The most common (greater than 10% incidence) adverse events reported in the grazoprevir/elbasvir and grazoprevir/elbasvir plus RBV arms, respectively, were fatigue (19%, 27%), headache (21%, 20%) and nausea (9%, 14%).
16 week arms
Of the 211 patients enrolled in the 16 week arms, 105 patients received grazoprevir/elbasvir only and 106 patients received grazoprevir/elbasvir plus RBV. In the grazoprevir/elbasvir only arm, 46 percent were infected with chronic HCV GT1a, 46 percent with GT1b or other GT1, five percent with GT4 and four percent with GT6. Overall, 36 percent of patients had liver cirrhosis. Among those in the grazoprevir/elbasvir plus RBV arm, 55 percent were infected with chronic HCV GT1a, 36 percent with GT1b or other GT1, eight percent with GT4, and two percent with GT6. Overall, 35 percent 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 adverse events were reported in three patients in the grazoprevir/elbasvir only arm (3%) and four patients in the grazoprevir/elbasvir plus RBV arm (4%). The most common (greater than 10% incidence) adverse events reported in the grazoprevir/elbasvir and grazoprevir/elbasvir plus RBV arms, respectively, were fatigue (16%, 30%), headache (19%, 19%) and nausea (4%,17%).
About the C-EDGE Program
C-EDGE is the Phase 3 clinical development program for Merck’s investigational HCV treatment grazoprevir/elbasvir comprising five studies with more than 1,700 patients across more than 25 countries. These studies are evaluating grazoprevir/elbasvir in multiple genotypes (GT1, 4 and 6) and diverse patient populations, including difficult-to-treat patients such as: treatment-experienced, patients with cirrhosis, HIV/HCV co-infection, advanced chronic kidney disease, inherited blood disorders, and those receiving opiate substitution therapies.
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