Merck, known as MSD outside of the United States and Canada, today announced the presentation of results from C-EDGE Head-to-Head, the company’s comparative, Phase 3, open-label clinical trial evaluating the efficacy and safety of ZEPATIER (elbasvir and grazoprevir) 50mg/100mg tablets versus a regimen of sofosbuvir 400mg tablets plus peginterferon and ribavirin (pegIFN/RBV) in treatment-naïve and pegIFN/RBV treatment-experienced patients with chronic hepatitis C (HCV) genotype (GT) 1 or GT4 infection (abstract #PS002). In this study, ZEPATIER demonstrated superiority on efficacy and safety endpoints compared to sofosbuvir plus pegIFN/RBV, based on pre-specified analyses. In the full analysis set (FAS) (n=255), the efficacy endpoint of sustained virologic response (SVR) 12 weeks after the completion of therapy (SVR12, considered virologic cure) was achieved in 99 percent (128/129) of patients receiving ZEPATIER for 12 weeks versus 90 percent (114/126) of patients receiving sofosbuvir plus pegIFN/RBV for 12 weeks. The study’s safety endpoint was the frequency of pre-specified (Tier 1) safety events focusing on tolerability, hematologic side effects, and liver-related laboratory abnormalities. ZEPATIER – Merck’s once-daily, fixed-dose combination tablet indicated with or without RBV for the treatment of chronic HCV GT1 or GT4 infection in adults – was approved by the U.S. Food and Drug Administration (FDA) on Jan. 28, 2016, based in part on prior studies from the Phase 3 program. The results of C-EDGE Head-to-Head will be featured today in the official press program at The International Liver Congress 2016.
“Overall in this study, the elbasvir and grazoprevir regimen showed superior SVR rates and improvement on pre-specified safety endpoints compared to the sofosbuvir plus peginterferon and ribavirin regimen in these genotype 1- or 4-infected patients,” said Dr. Jan Sperl, Department of Hepatogastroenterology, Institute for Clinical and Experimental Health, Prague, Czech Republic and lead study investigator. “Sofosbuvir in combination with peginterferon and ribavirin continues to be a prescribed treatment regimen in many regions, and this comparative study versus combination treatment with elbasvir and grazoprevir provides interesting and important insights.”
C-EDGE Head-to-Head is a comparative Phase 3, randomized, open-label, parallel-group trial conducted at multiple sites in the European Union, Norway and Turkey, and was designed to evaluate the efficacy and safety of 12 weeks of ZEPATIER (elbasvir and grazoprevir) versus a 12 week treatment regimen of sofosbuvir plus pegIFN/RBV. The trial enrolled treatment-naïve and pegIFN/RBV treatment-experienced patients, with or without cirrhosis, with chronic HCV GT1 or GT4 infection. Investigators were to enroll only patients whom, in their opinion, were appropriate candidates for 12 weeks of pegIFN/RBV-based therapy; this assessment included consideration of factors associated with lower response rates to interferon-based therapies (e.g., advanced fibrosis/cirrhosis, high baseline viral concentrations, black race, IL28B non-CC genotype, or prior null-response to pegIFN/RBV therapy). The study randomized 255 GT1- or GT4-infected patients to 12 weeks of treatment with either ZEPATIER (elbasvir and grazoprevir) 50mg/100mg tablets (n=129) or sofosbuvir 400mg tablets plus pegIFN/RBV (n=126). Overall, at baseline, 17 percent of patients had compensated cirrhosis; 67 percent had HCV RNA greater than 800,000 IU/mL; 99 percent were white; 78 percent had IL28B non-CC genotype; and approximately 25 percent had failed prior treatment with pegIFN/RBV (10percent prior null-responders, 5percent prior partial-responders, 10percent prior relapsers).
In the FAS (n=255), the efficacy analyses demonstrated superiority of ZEPATIER compared to sofosbuvir plus pegIFN/RBV, as measured by SVR12. 2 Higher SVR rates were observed among those receiving ZEPATIER (elbasvir and grazoprevir) in subgroups of patients who had previously experienced a non-response to pegIFN/RBV therapy and in those with cirrhosis, higher baseline viral load, or IL28B non-CC genotype. Efficacy results for the overall population as well as those for selected subgroups are shown in Table 1. In the ZEPATIER group, one patient (1percent) discontinued from the trial after completing treatment. There were no virologic failures in the ZEPATIER group. In the sofosbuvir plus pegIFN/RBV group, virologic failure occurred in 11 patients (9percent) and one patient (1percent) discontinued from the trial after the first week of treatment.
Source: Merck
Filed Under: Drug Discovery
