In the Journals

Triple therapy DAA leads to SVR after virologic relapse

The direct-acting antiviral combination of grazoprevir, ruzasvir and uprifosbuvir, with or without ribavirin, for either 16 or 24 weeks was safe and effective for patients with hepatitis C who had previously failed NS5A inhibitor-containing treatment, according to results of two phase 2 studies.

“People with hepatitis C virus (HCV) infection who have failed treatment with an all-oral, direct-acting antiviral (DAA) regimen represent a challenging treatment population. Re-treatment using the same regimen results in suboptimal efficacy; thus, these people have limited re-treatment options,” David Wyles, MD, from the University of Colorado School of Medicine, and colleagues wrote. “Current guidelines suggest deferral of treatment in anticipation of better re-treatment options for people with [genotype 1] infection without an urgent indication for re-treatment who have failed treatment with an NS5A inhibitor-containing regimen.”

The open-label, multicenter evaluations consisted of the C-SURGE and C-CREST Part C studies. The researchers enrolled 93 patients with HCV genotype 1 into either a 16-week or 24-week treatment cohort of the C-SURGE study. In the C-CREST Part C study, they enrolled 24 patients who had experienced virologic relapse after participation in the C-CREST Part A study.

In the C-SURGE study, 76% of the patients had previously failed treatment with Harvoni (ledipasvir/sofosbuvir, Gilead Sciences) and 24% had failed treatment with Zepatier (elbasvir/grazoprevir, Merck). Forty-three of 44 patients in the 16-week arm and all patients in the 24-week arm achieved sustained virologic response at 12 weeks. One patient from the 16-week arm withdrew for reasons unrelated to treatment. Additionally, the researchers determined that the presence of resistance-associated substitutions at baseline did not impact SVR.

Fourteen of the 24 patients in the C-CREST Part C study received elbasvir and 10 had received ruzasvir as their NS5A inhibitor during the previous Part A study. Two patients had HCV genotype 1, 14 had genotype 2 and eight had genotype 3. Twenty-three of the 24 patients achieved sustained virologic response at 12 weeks. One of the patients with genotype 2 discontinued treatment due to serious adverse events including vomiting and tachycardia that were deemed drug-related by the investigator. The researchers note, however, that although the adverse events were considered drug-related, it was not clear to which drug the symptoms were related.

“The main limitation of the present studies was the relatively small number of participants, and hence the small participant subgroups. All participants in C-CREST Part C were noncirrhotic, whereas approximately 42% of those in C-SURGE had compensated cirrhosis,” the researchers wrote. “Future studies are needed to evaluate shorter durations of therapy and better define the role of [ribavirin], since an effective short-duration regimen without ribavirin for the retreatment of participants who have failed prior DAA therapies would fulfill a current unmet need.” – by Talitha Bennett

Disclosure: Wyles reports financial relationships with AbbVie, Bristol-Myers Squibb, Gilead Sciences and Merck. Please see the full study for the other researchers’ relevant financial disclosures.

The direct-acting antiviral combination of grazoprevir, ruzasvir and uprifosbuvir, with or without ribavirin, for either 16 or 24 weeks was safe and effective for patients with hepatitis C who had previously failed NS5A inhibitor-containing treatment, according to results of two phase 2 studies.

“People with hepatitis C virus (HCV) infection who have failed treatment with an all-oral, direct-acting antiviral (DAA) regimen represent a challenging treatment population. Re-treatment using the same regimen results in suboptimal efficacy; thus, these people have limited re-treatment options,” David Wyles, MD, from the University of Colorado School of Medicine, and colleagues wrote. “Current guidelines suggest deferral of treatment in anticipation of better re-treatment options for people with [genotype 1] infection without an urgent indication for re-treatment who have failed treatment with an NS5A inhibitor-containing regimen.”

The open-label, multicenter evaluations consisted of the C-SURGE and C-CREST Part C studies. The researchers enrolled 93 patients with HCV genotype 1 into either a 16-week or 24-week treatment cohort of the C-SURGE study. In the C-CREST Part C study, they enrolled 24 patients who had experienced virologic relapse after participation in the C-CREST Part A study.

In the C-SURGE study, 76% of the patients had previously failed treatment with Harvoni (ledipasvir/sofosbuvir, Gilead Sciences) and 24% had failed treatment with Zepatier (elbasvir/grazoprevir, Merck). Forty-three of 44 patients in the 16-week arm and all patients in the 24-week arm achieved sustained virologic response at 12 weeks. One patient from the 16-week arm withdrew for reasons unrelated to treatment. Additionally, the researchers determined that the presence of resistance-associated substitutions at baseline did not impact SVR.

Fourteen of the 24 patients in the C-CREST Part C study received elbasvir and 10 had received ruzasvir as their NS5A inhibitor during the previous Part A study. Two patients had HCV genotype 1, 14 had genotype 2 and eight had genotype 3. Twenty-three of the 24 patients achieved sustained virologic response at 12 weeks. One of the patients with genotype 2 discontinued treatment due to serious adverse events including vomiting and tachycardia that were deemed drug-related by the investigator. The researchers note, however, that although the adverse events were considered drug-related, it was not clear to which drug the symptoms were related.

“The main limitation of the present studies was the relatively small number of participants, and hence the small participant subgroups. All participants in C-CREST Part C were noncirrhotic, whereas approximately 42% of those in C-SURGE had compensated cirrhosis,” the researchers wrote. “Future studies are needed to evaluate shorter durations of therapy and better define the role of [ribavirin], since an effective short-duration regimen without ribavirin for the retreatment of participants who have failed prior DAA therapies would fulfill a current unmet need.” – by Talitha Bennett

Disclosure: Wyles reports financial relationships with AbbVie, Bristol-Myers Squibb, Gilead Sciences and Merck. Please see the full study for the other researchers’ relevant financial disclosures.