Merck has reported that its Zepatier (Elbasvir and Grazoprevir) showed superiority on efficacy and safety endpoints compared to sofosbuvir plus peginterferon and ribavirin treatment regimen in a Phase 3 trial.
The company's comparative, Phase 3, open-label clinical trial evaluated 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.
In the full analysis set (FAS), the efficacy endpoint of sustained virologic response (SVR) 12 weeks after the completion of therapy was achieved in 99% (128/129) of patients receiving Zepatier for 12 weeks versus 90% (114/126) of patients receiving sofosbuvir plus pegIFN/RBV for 12 weeks.
The study's safety endpoint was the regularity of pre-specified safety events focusing on tolerability, hematologic side effects, and liver-related laboratory abnormalities.
Zepatier was approved by the US Food and Drug Administration (FDA) in January, based in part on prior studies from the Phase 3 programme.
Merck's Zepatier is a once-daily, fixed-dose combination tablet indicated with or without RBV for treatment of chronic HCV GT1 or GT4 infection in adults.
C-EDGE Head-to-Head, which is a comparative Phase 3, randomised, open-label, parallel-group trial conducted at multiple sites in the European Union, Norway and Turkey, 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 study randomised 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% of patients had compensated cirrhosis; 67% had HCV RNA greater than 800,000 IU/mL; 99% were white; 78% had IL28B non-CC genotype; and around 25% had failed prior treatment with pegIFN/RBV (10% prior null-responders, 5% prior partial-responders, 10% prior relapsers).
In the FAS, the efficacy analyses showed superiority of Zepatier compared to Sofosbuvir plus pegIFN/RBV, as measured by SVR12.
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.
In the Zepatier group, one patient discontinued from the trial after completing treatment and there were no virologic failures reported in the Zepatier group.
In the sofosbuvir plus pegIFN/RBV group, virologic failure occurred in 11 patients (9%) and one patient discontinued from the trial after the first week of treatment.