Experimental Hepatitis C Drug Shows 95% Cure Rates in Previously Untreated Patients

Merck's once-daily treatment regimen of grazoprevir and elbasvir may bring added competition to HCV drug market.

Merck’s once-daily treatment regimen of grazoprevir and elbasvir may bring added competition to HCV drug market.

An experimental hepatitis C virus (HCV) therapy manufactured by Merck may soon challenge the stranglehold on the market held by treatments such as Sovaldi, Harvoni, and Viekira Pak.

In a phase 2 clinical trial called C-SAVAGE, the combination of grazoprevir and elbasvir with ribavirin showed high rates of sustained virologic response 12 weeks (SVR12) following the completion of treatment in patients infected with chronic HCV genotype 1 with or without liver cirrhosis who previously failed combination therapy with a direct acting antiviral agent.

Meanwhile, another phase 2 clinical trial, called C-SWIFT, analyzed grazoprevir and elbasvir in combination with sofosbuvir 400mg in previously untreated patients with or without liver cirrhosis who were chronically infected with HCV genotype 1 or genotype 3, which presented proof-of-concept for possibly shortening HCV treatment duration under 12 weeks.

“We continue to advance our Phase 3 clinical program for grazoprevir/elbasvir evaluating diverse patient populations with chronic HCV infection, including those widely considered among the most difficult to treat,” Eliav Barr, MD, vice president of infectious diseases at Merck Research Laboratories said in a press release. “Findings from these phase 2 studies formed part of the basis for our decision to rapidly advance our large and comprehensive clinical development program that incorporates studies dedicated to patient populations with specific unmet medical needs.”

The combination therapy is a once-daily single tablet regimen consisting of the NS3/4A protease inhibitor grazoprevir and the NS5A replication complex inhibitor elbasvir. The grazoprevir and elbasvir combination is being evaluated across multiple HCV genotypes and in patients with difficult-to-treat comorbidities, including a co-infection with HIV/HCV, advanced chronic kidney disease, inherited blood disorders, liver cirrhosis, and patients on opiate substitution therapy.

C-SAVAGE was a single arm, open label trial that evaluated the efficacy and safety of treatment with grazoprevir and elbasvir plus ribavirin over a 12-week duration in 79 patients who previously failed treatment with peginterferon and ribavirin combined with boceprevir, simeprevir, or telaprevir. Of the 79 patients receiving one or more doses of grazoprevir and elbasvir, 43% had liver cirrhosis.

After 12 weeks of treatment with the experimental therapy, 96% of patients achieved SVR12. Furthermore, 94% of patients with compensated cirrhosis achieved SVR12.

Virologic failure occurred in 3 patients, all of whom had resistance-associated variants at baseline and relapsed after the treatment cycle was completed.

The most common adverse events were fatigue (28%), headache (19%), asthenia (15%) and nausea (12%). There were 5 serious adverse events reported, but none these were considered related to the treatment. Another patient discontinued treatment due to an adverse event that was not considered drug-related.

C-SWIFT was a proof-of-concept open label clinical trial that evaluated the efficacy and safety of grazoprevir and elbasvir plus sofosbuvir over shorter treatment durations. The trial included previously untreated patients with or without liver cirrhosis who received the combination for 4, 6, or 8 weeks, and previously untreated patients with or without liver cirrhosis who were treated for 8 or 12 weeks.

In patients with genotype 1, a virologic relapse occurred in 20 of 30 non-cirrhotic patients in the 4-week treatment cohort, in 4 of 30 non-cirrhotic and 4 of 20 cirrhotic patients in the 6-week treatment cohort, and in 1 of 18 cirrhotic patients in the 8-week treatment cohort. In patients with genotype 3, virologic relapse occurred in 1 of 15 non-cirrhotic patients in the 8-week treatment cohort, and in 1 of 11 cirrhotic patients in the 12-week treatment cohort.

There were no reported cases of virologic breakthrough during the trial.