Elbasvir, grazoprevir beat HCV despite compensated cirrhosis

Twelve weeks of combination therapy with elbasvir and grazoprevir (EBR/GZR) achieved sustained virologic response in 98% of treatment-naive patients with compensated cirrhosis and chronic hepatitis C (HCV) genotype 1, 4, or 6 infections, and in 89% of treatment-experienced patients, according to a pooled analysis of six industry-sponsored trials.

Concomitant ribavirin offered “no incremental benefit” for treatment-naive patients, while 16 or 18 weeks of EBR and GZR with ribavirin achieved SVR12 in 100% of treatment-experienced patients, wrote Ira M. Jacobson, MD, of Mount Sinai Beth Israel and Icahn School of Medicine at Mount Sinai, New York, and his associates. The report was published in the May issue of Gastroenterology (doi: 10.1053/j.gastro.2017.01.050).

Regardless of treatment history, genotype 1a patients with resistance-associated variants (RAV) in HCV nonstructural protein 5A (NS5A) needed ribavirin to achieve sustained virologic response (SVR) rates above 90%, the researchers emphasized. “Both patients with HCV genotype 1a infection with baseline RAVs who received 16 or 18 weeks of EBR/GZR and ribavirin achieved SVR12,” the researchers noted. Elbasvir is an HCV NS5A inhibitor, and GZR is an HCV NS3/4A protease inhibitor. In 2016, the Food and Drug Administration approved them in combination (Zepatier) for chronic genotype 1 and genotype 4 HCV. Studies have confirmed the benefits of treating HCV even when patients have cirrhosis, but they can be challenging to treat, especially if they have already failed a regimen that included a direct-acting antiviral agent, the investigators noted.

To explore the efficacy of EBR/GZR in compensated, Child-Pugh A cirrhosis, they studied 402 such patients with HCV genotype 1, 4, or 6 infections whose baseline HCV RNA level exceeded 10,000 IU. Patients had participated in one of six phase II/III clinical trials and had received EBR/GZR 50 mg/100 mg once daily for 12-18 weeks, with or without ribavirin (800-1400 mg/day based on body weight). Treatment-naive patients received 12 weeks of treatment, while treatment-experienced patients received 12, 16, or 18 weeks of treatment.

Twelve weeks of ribavirin did not boost SVR for either treatment-naive (90%) or treatment-experienced patients (91%), the researchers said. However, all 49 treatment-experienced patients who received EBR/GZR plus ribavirin for 16 or 18 weeks achieved SVR12, compared to 94% of patients who received EBR/GZR without ribavirin for 16 or 18 weeks.

Virologic failure was more common with HCV genotype 1a infections than with genotype 1b or 4 infection, especially if patients previously had not responded to interferon, the researchers noted. Eight of 11 (73%) patients with HCV genotype 1a infection and baseline NS5A RAVs achieved SVR12, compared with 98% of GT1a-infected patients without RAVs at baseline. But EBR/GZR was effective in various other subgroups, including patients with less than 100,000 platelets per microL, serum albumin below 3.5 g/dL, and FibroScan scores below 25 kPa. These findings suggest that EBR/GZR remains effective in patients with advanced compensated cirrhosis, the investigators said.

Most patients tolerated therapy, but six stopped treatment because of adverse events, including one episode of severe, possibly treatment-related abdominal pain. Also, four patients had late, asymptomatic rises in alanine aminotransferase (ALT) after first normalizing on treatment, and one patient stopped treatment because of grade 4 ALT elevation with eosinophilia. “There were no decompensation events in this generally healthy cirrhotic population, and no other evidence of declining liver function while on treatment,” the researchers added.

The integrated analysis was not prespecified, nor was it powered to compare outcomes between treatment arms. Only three patients had genotype 6 infection, and all were treatment-experienced. Only 23 patients had genotype 4 infection. Also, most patients had well-compensated cirrhosis. Finally, the trials varied in terms of how they defined cirrhosis, the investigators noted.

Merck, which funded the study, makes elbasvir and grazoprevir. The investigators acknowledged medical writing and editorial assistance from ApotheCom, which Merck funded. Dr. Jacobson disclosed consulting relationships and grant funding from Merck, AbbVie, Bristol-Myers Squibb, Gilead, Intercept, Janssen, and Trek.

Twelve weeks of combination therapy with elbasvir and grazoprevir (EBR/GZR) achieved sustained virologic response in 98% of treatment-naive patients with compensated cirrhosis and chronic hepatitis C (HCV) genotype 1, 4, or 6 infections, and in 89% of treatment-experienced patients, according to a pooled analysis of six industry-sponsored trials.

Concomitant ribavirin offered “no incremental benefit” for treatment-naive patients, while 16 or 18 weeks of EBR and GZR with ribavirin achieved SVR12 in 100% of treatment-experienced patients, wrote Ira M. Jacobson, MD, of Mount Sinai Beth Israel and Icahn School of Medicine at Mount Sinai, New York, and his associates. The report was published in the May issue of Gastroenterology (doi: 10.1053/j.gastro.2017.01.050).

Regardless of treatment history, genotype 1a patients with resistance-associated variants (RAV) in HCV nonstructural protein 5A (NS5A) needed ribavirin to achieve sustained virologic response (SVR) rates above 90%, the researchers emphasized. “Both patients with HCV genotype 1a infection with baseline RAVs who received 16 or 18 weeks of EBR/GZR and ribavirin achieved SVR12,” the researchers noted. Elbasvir is an HCV NS5A inhibitor, and GZR is an HCV NS3/4A protease inhibitor. In 2016, the Food and Drug Administration approved them in combination (Zepatier) for chronic genotype 1 and genotype 4 HCV. Studies have confirmed the benefits of treating HCV even when patients have cirrhosis, but they can be challenging to treat, especially if they have already failed a regimen that included a direct-acting antiviral agent, the investigators noted.

To explore the efficacy of EBR/GZR in compensated, Child-Pugh A cirrhosis, they studied 402 such patients with HCV genotype 1, 4, or 6 infections whose baseline HCV RNA level exceeded 10,000 IU. Patients had participated in one of six phase II/III clinical trials and had received EBR/GZR 50 mg/100 mg once daily for 12-18 weeks, with or without ribavirin (800-1400 mg/day based on body weight). Treatment-naive patients received 12 weeks of treatment, while treatment-experienced patients received 12, 16, or 18 weeks of treatment.

Twelve weeks of ribavirin did not boost SVR for either treatment-naive (90%) or treatment-experienced patients (91%), the researchers said. However, all 49 treatment-experienced patients who received EBR/GZR plus ribavirin for 16 or 18 weeks achieved SVR12, compared to 94% of patients who received EBR/GZR without ribavirin for 16 or 18 weeks.

Virologic failure was more common with HCV genotype 1a infections than with genotype 1b or 4 infection, especially if patients previously had not responded to interferon, the researchers noted. Eight of 11 (73%) patients with HCV genotype 1a infection and baseline NS5A RAVs achieved SVR12, compared with 98% of GT1a-infected patients without RAVs at baseline. But EBR/GZR was effective in various other subgroups, including patients with less than 100,000 platelets per microL, serum albumin below 3.5 g/dL, and FibroScan scores below 25 kPa. These findings suggest that EBR/GZR remains effective in patients with advanced compensated cirrhosis, the investigators said.

Most patients tolerated therapy, but six stopped treatment because of adverse events, including one episode of severe, possibly treatment-related abdominal pain. Also, four patients had late, asymptomatic rises in alanine aminotransferase (ALT) after first normalizing on treatment, and one patient stopped treatment because of grade 4 ALT elevation with eosinophilia. “There were no decompensation events in this generally healthy cirrhotic population, and no other evidence of declining liver function while on treatment,” the researchers added.

The integrated analysis was not prespecified, nor was it powered to compare outcomes between treatment arms. Only three patients had genotype 6 infection, and all were treatment-experienced. Only 23 patients had genotype 4 infection. Also, most patients had well-compensated cirrhosis. Finally, the trials varied in terms of how they defined cirrhosis, the investigators noted.

Merck, which funded the study, makes elbasvir and grazoprevir. The investigators acknowledged medical writing and editorial assistance from ApotheCom, which Merck funded. Dr. Jacobson disclosed consulting relationships and grant funding from Merck, AbbVie, Bristol-Myers Squibb, Gilead, Intercept, Janssen, and Trek.

Twelve weeks of combination therapy with elbasvir and grazoprevir (EBR/GZR) achieved sustained virologic response in 98% of treatment-naive patients with compensated cirrhosis and chronic hepatitis C (HCV) genotype 1, 4, or 6 infections, and in 89% of treatment-experienced patients, according to a pooled analysis of six industry-sponsored trials.

Concomitant ribavirin offered “no incremental benefit” for treatment-naive patients, while 16 or 18 weeks of EBR and GZR with ribavirin achieved SVR12 in 100% of treatment-experienced patients, wrote Ira M. Jacobson, MD, of Mount Sinai Beth Israel and Icahn School of Medicine at Mount Sinai, New York, and his associates. The report was published in the May issue of Gastroenterology (doi: 10.1053/j.gastro.2017.01.050).

Regardless of treatment history, genotype 1a patients with resistance-associated variants (RAV) in HCV nonstructural protein 5A (NS5A) needed ribavirin to achieve sustained virologic response (SVR) rates above 90%, the researchers emphasized. “Both patients with HCV genotype 1a infection with baseline RAVs who received 16 or 18 weeks of EBR/GZR and ribavirin achieved SVR12,” the researchers noted. Elbasvir is an HCV NS5A inhibitor, and GZR is an HCV NS3/4A protease inhibitor. In 2016, the Food and Drug Administration approved them in combination (Zepatier) for chronic genotype 1 and genotype 4 HCV. Studies have confirmed the benefits of treating HCV even when patients have cirrhosis, but they can be challenging to treat, especially if they have already failed a regimen that included a direct-acting antiviral agent, the investigators noted.

To explore the efficacy of EBR/GZR in compensated, Child-Pugh A cirrhosis, they studied 402 such patients with HCV genotype 1, 4, or 6 infections whose baseline HCV RNA level exceeded 10,000 IU. Patients had participated in one of six phase II/III clinical trials and had received EBR/GZR 50 mg/100 mg once daily for 12-18 weeks, with or without ribavirin (800-1400 mg/day based on body weight). Treatment-naive patients received 12 weeks of treatment, while treatment-experienced patients received 12, 16, or 18 weeks of treatment.

Twelve weeks of ribavirin did not boost SVR for either treatment-naive (90%) or treatment-experienced patients (91%), the researchers said. However, all 49 treatment-experienced patients who received EBR/GZR plus ribavirin for 16 or 18 weeks achieved SVR12, compared to 94% of patients who received EBR/GZR without ribavirin for 16 or 18 weeks.

Virologic failure was more common with HCV genotype 1a infections than with genotype 1b or 4 infection, especially if patients previously had not responded to interferon, the researchers noted. Eight of 11 (73%) patients with HCV genotype 1a infection and baseline NS5A RAVs achieved SVR12, compared with 98% of GT1a-infected patients without RAVs at baseline. But EBR/GZR was effective in various other subgroups, including patients with less than 100,000 platelets per microL, serum albumin below 3.5 g/dL, and FibroScan scores below 25 kPa. These findings suggest that EBR/GZR remains effective in patients with advanced compensated cirrhosis, the investigators said.

Most patients tolerated therapy, but six stopped treatment because of adverse events, including one episode of severe, possibly treatment-related abdominal pain. Also, four patients had late, asymptomatic rises in alanine aminotransferase (ALT) after first normalizing on treatment, and one patient stopped treatment because of grade 4 ALT elevation with eosinophilia. “There were no decompensation events in this generally healthy cirrhotic population, and no other evidence of declining liver function while on treatment,” the researchers added.

The integrated analysis was not prespecified, nor was it powered to compare outcomes between treatment arms. Only three patients had genotype 6 infection, and all were treatment-experienced. Only 23 patients had genotype 4 infection. Also, most patients had well-compensated cirrhosis. Finally, the trials varied in terms of how they defined cirrhosis, the investigators noted.

Merck, which funded the study, makes elbasvir and grazoprevir. The investigators acknowledged medical writing and editorial assistance from ApotheCom, which Merck funded. Dr. Jacobson disclosed consulting relationships and grant funding from Merck, AbbVie, Bristol-Myers Squibb, Gilead, Intercept, Janssen, and Trek.