In the Journals

Zepatier highly effective for inducing SVR in HCV patients with prior treatment failure

Zepatier treatment for 12 weeks, with or without ribavirin, was highly effective for induction of sustained virologic response in patients infected with hepatitis C genotypes 1, 4 or 6, who failed prior peg-interferon and ribavirin treatments, according to the results of the C-EDGE Treatment Experienced trial.

SVR12 was also achieved by patients with cirrhosis or a null response to previous treatment in this trial, and the treatment was generally well tolerated.

Zepatier (grazoprevir/elbasvir, Merck), is a once-daily, fixed-dose combination tablet containing 50 mg of elbasvir, an NS5A inhibitor, and 100 mg of grazoprevir, an NS3/4A protease inhibitor, which was approved for HCV genotypes 1 and 4 in January 2016.

To evaluate the effectiveness of elbasvir/grazoprevir in treatment-experienced patients infected with HCV genotypes 1, 4 or 6, Paul Y. Kwo, MD, FACG, FAASLD, of the division of gastroenterology/hepatology in the department of medicine at Stanford University School of Medicine, Palo Alto, Calif., and colleagues performed an international multicenter, open-label phase 3 randomized controlled trial of the drug regimen in this difficult to treat patient population.

Paul Y. Kwo
Paul Y. Kwo

“Data from the phase 2 C-WORTHY study indicate that an 18-week regimen of [elbasvir/grazoprevir plus ribavirin] may be sufficient to achieve high rates of SVR12 in a previously treated patient population, including those with cirrhosis,” Kwo and colleagues wrote. “We therefore hypothesized that the combination … could achieve high SVR12 rates when given for only 12-16 weeks which, at the time that the study was designed, would have afforded substantial benefit over the contemporaneous treatment options. At the time of the development of this protocol, this was the first phase 3 trial to explore a lengthened duration shorter than 24 weeks.”

Stratified by cirrhosis status and type of previous treatment failure, researchers randomly assigned 420 patients (median age, 55 years; 68% white; 65% men; 35% with cirrhosis, 64% with a null or partial response to previous treatment with peg-interferon and ribavirin) to receive elbasvir/grazoprevir once per day, with or without ribavirin twice per day, for 12 or 16 weeks. SVR12 served as the primary endpoint, and the researchers compared groups with a reference SVR12 rate of 58%.

Overall, 92.4% of patients achieved SVR12 with 12 weeks of elbasvir/grazoprevir, and 94.2% of patients achieved SVR12 with 12 weeks of elbasvir/grazoprevir plus ribavirin. SVR12 was also achieved by 92.4% of patients with 16 weeks of elbasvir/grazoprevir and 98.1% of patients with 16 weeks of elbasvir/grazoprevir plus ribavirin.

Virologic failure occurred in 6.8% of patients with HCV genotype 1a, in none of the patients with genotype 1b and in 12.5% of patients with genotype 4 after treatment for 12 weeks without ribavirin.

Moreover, no patients with genotypes 1 and 4 who relapsed after treatment with peg-interferon and ribavirin experienced virologic failure after 12 weeks of treatment with elbasvir/grazoprevir, while 7.5% of patients infected with these genotypes who had a null or partial response to these prior therapies experienced virologic failure after 12 weeks of treatment with elbasvir/grazoprevir. No patients who received 16 weeks of treatment with ribavirin experienced virologic failure.

Fatigue (23.1%), headache (19.8%) and nausea (11%) were the most common adverse events.

“Treatment with [elbasvir/grazoprevir]-containing regimens was highly effective in the treatment of [genotypes] 1-, 4-, or 6-infected patients who failed prior [peg-interferon or ribavirin] therapy,” the researchers concluded. “Importantly, there was no difference in response rates between patients with and without cirrhosis, irrespective of therapy duration and with or without the addition of ribavirin.” – by Adam Leitenberger

Disclosures: Kwo reports he received grants and personal fees from Merck, AbbVie, BMS, Gilead and Janssen. Please see the study for a full list of all other researchers’ relevant financial disclosures.

Zepatier treatment for 12 weeks, with or without ribavirin, was highly effective for induction of sustained virologic response in patients infected with hepatitis C genotypes 1, 4 or 6, who failed prior peg-interferon and ribavirin treatments, according to the results of the C-EDGE Treatment Experienced trial.

SVR12 was also achieved by patients with cirrhosis or a null response to previous treatment in this trial, and the treatment was generally well tolerated.

Zepatier (grazoprevir/elbasvir, Merck), is a once-daily, fixed-dose combination tablet containing 50 mg of elbasvir, an NS5A inhibitor, and 100 mg of grazoprevir, an NS3/4A protease inhibitor, which was approved for HCV genotypes 1 and 4 in January 2016.

To evaluate the effectiveness of elbasvir/grazoprevir in treatment-experienced patients infected with HCV genotypes 1, 4 or 6, Paul Y. Kwo, MD, FACG, FAASLD, of the division of gastroenterology/hepatology in the department of medicine at Stanford University School of Medicine, Palo Alto, Calif., and colleagues performed an international multicenter, open-label phase 3 randomized controlled trial of the drug regimen in this difficult to treat patient population.

Paul Y. Kwo
Paul Y. Kwo

“Data from the phase 2 C-WORTHY study indicate that an 18-week regimen of [elbasvir/grazoprevir plus ribavirin] may be sufficient to achieve high rates of SVR12 in a previously treated patient population, including those with cirrhosis,” Kwo and colleagues wrote. “We therefore hypothesized that the combination … could achieve high SVR12 rates when given for only 12-16 weeks which, at the time that the study was designed, would have afforded substantial benefit over the contemporaneous treatment options. At the time of the development of this protocol, this was the first phase 3 trial to explore a lengthened duration shorter than 24 weeks.”

Stratified by cirrhosis status and type of previous treatment failure, researchers randomly assigned 420 patients (median age, 55 years; 68% white; 65% men; 35% with cirrhosis, 64% with a null or partial response to previous treatment with peg-interferon and ribavirin) to receive elbasvir/grazoprevir once per day, with or without ribavirin twice per day, for 12 or 16 weeks. SVR12 served as the primary endpoint, and the researchers compared groups with a reference SVR12 rate of 58%.

Overall, 92.4% of patients achieved SVR12 with 12 weeks of elbasvir/grazoprevir, and 94.2% of patients achieved SVR12 with 12 weeks of elbasvir/grazoprevir plus ribavirin. SVR12 was also achieved by 92.4% of patients with 16 weeks of elbasvir/grazoprevir and 98.1% of patients with 16 weeks of elbasvir/grazoprevir plus ribavirin.

Virologic failure occurred in 6.8% of patients with HCV genotype 1a, in none of the patients with genotype 1b and in 12.5% of patients with genotype 4 after treatment for 12 weeks without ribavirin.

Moreover, no patients with genotypes 1 and 4 who relapsed after treatment with peg-interferon and ribavirin experienced virologic failure after 12 weeks of treatment with elbasvir/grazoprevir, while 7.5% of patients infected with these genotypes who had a null or partial response to these prior therapies experienced virologic failure after 12 weeks of treatment with elbasvir/grazoprevir. No patients who received 16 weeks of treatment with ribavirin experienced virologic failure.

Fatigue (23.1%), headache (19.8%) and nausea (11%) were the most common adverse events.

“Treatment with [elbasvir/grazoprevir]-containing regimens was highly effective in the treatment of [genotypes] 1-, 4-, or 6-infected patients who failed prior [peg-interferon or ribavirin] therapy,” the researchers concluded. “Importantly, there was no difference in response rates between patients with and without cirrhosis, irrespective of therapy duration and with or without the addition of ribavirin.” – by Adam Leitenberger

Disclosures: Kwo reports he received grants and personal fees from Merck, AbbVie, BMS, Gilead and Janssen. Please see the study for a full list of all other researchers’ relevant financial disclosures.